J. Cardiovasc. Dev. Dis., Volume 11, Issue 1 (January 2024) – 33 articles

Background: Current European guidelines support transcatheter aortic valve implantation (TAVI) in intermediate-to-low-risk patients ≥75 years-old, but its prognostic relevance is unknown. Methods: Intermediate-to-low-risk (The Society of Thoracic Surgeons score <8%) patients enrolled in the HORSE registry were included. We compared the populations aged under 75 with those over 75. The primary endpoint was all-cause mortality. Results: A total of 2685 patients were included: 280 (8.6%) < 75 and 2405 ≥ 75 years. Through a mean follow-up of 437 ± 381 days, 198 (8.2%) and 23 (8.2%) patients died in the two arms without statistically significant differences (log-rank p = 0.925). At Cox regression analysis, age did not predict the occurrence of all-cause death, neither as a continuous variable (HR 1.01, 95% CI 0.99–1.04, p = 0.294) nor dichotomizing according to the prespecified cutoff of 75 years (HR 0.97, 95% CI 0.63–1.51, p = 0.924). Time-to-event ROC curves showed low accuracy of age to predict all-cause mortality (area under the curve of 0.54 for both 1-year and 2-year outcomes). Conclusions: TAVI has comparable benefits across age strata for intermediate-to-low-risk patients. The age cutoff suggested by the current guidelines is not predictive of the risk of adverse events during hospital stays or of all-cause mortality through a mid-term follow-up. Full article

(1) Background: This study examines frailty’s impact on proximal aortic surgery outcomes. (2) Methods: All patients with a thoracic aortic aneurysm who underwent aortic root, ascending aorta, or arch surgery from the 2016–2017 National Inpatient Sample were included. Frailty was defined by the Adjusted Clinical Groups Frailty Indicator. Outcomes of interest included in-hospital mortality and a composite of death, stroke, acute kidney injury (AKI), and major bleeding (MACE). (3) Results: Among 5745 patients, 405 (7.0%) met frailty criteria. Frail patients were older, with higher rates of chronic pulmonary disease, diabetes, and chronic kidney disease. There was no difference in in-hospital death (4.9% vs. 2.4%, p = 0.169); however, the frail group exhibited higher rates of stroke and AKI. Frail patients had a longer length of stay (17 vs. 8 days), and higher rates of non-home discharge (74.1% vs. 54.3%) than non-frail patients (both p < 0.001). Sensitivity analysis confirmed increased morbidity and mortality in frail individuals. After adjusting for patient comorbidities and hospital characteristics, frailty independently predicted MACE (OR 4.29 [1.88–9.78], p = 0.001), while age alone did not (OR 1.00 [0.99–1.02], p = 0.568). Urban teaching center status predicted a lower risk of MACE (OR 0.27 [0.08–0.94], p = 0.039). (4) Conclusions: Frailty is associated with increased morbidity in proximal aortic surgery and is a more significant predictor of mortality than age. Coordinated treatment in urban institutions may enhance outcomes for this high-risk group. Full article

The prenatal diagnosis of congenital heart disease (CHD) represents, for both parents, a particularly stressful and traumatic life event from a psychological point of view. The present review sought to summarize the findings of the most relevant literature on the psychological impact of prenatal diagnosis of CHD on parents, describing the most common mechanisms employed in order to face this unexpected finding. We also highlight the importance of counseling and the current gaps in the effects of psychological support on this population. Full article

Background: Recent data have suggested that global longitudinal strain (GLS) could be useful for risk stratification of patients with severe aortic stenosis (AS). In this study, we aimed to investigate the prognostic role of GLS in patients with AS and also its incremental value in relation to left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE). Methods: We analysed all consecutive patients with AS and LGE-CMR in our institution. Survival data were obtained from office of national statistics, a national body where all deaths in England are registered by law. Death certificates were obtained from the general register office. Results: Some 194 consecutive patients with aortic stenosis were investigated with CMR at baseline and followed up for 7.3 ± 4 years. On multivariate Cox regression analysis, only increasing age remained significant for both all-cause and cardiac mortality, while LGE (any pattern) retained significance for all-cause mortality and had a trend to significance for cardiac mortality. Kaplan–Meier survival analysis demonstrated that patients in the best and middle GLS tertiles had significantly better mortality compared to patients in the worst GLS tertiles. Importantly though, sequential Cox proportional-hazard analysis demonstrated that GLS did not have significant incremental prognostic value for all-cause mortality or cardiac mortality in addition to LVEF and LGE. Conclusions: Our study has demonstrated that age and LGE but not GLS are significant poor prognostic indicators in patients with moderate and severe AS. Full article

Heart transplantation is currently the most effective treatment for end-stage heart failure; however, the shortage in donor hearts constrains the undertaking of transplantation. Mechanical circulatory support (MCS) technology has made rapid progress in recent years, providing diverse therapeutic options and alleviating the dilemma of donor heart shortage. The ventricular assist device (VAD), as an important category of MCS, demonstrates promising applications in bridging heart transplantation, destination therapy, and bridge-to-decision. VADs can be categorized as durable VADs (dVADs) and temporary VADs (tVADs), according to the duration of assistance. With the technological advancement and clinical application experience accumulated, VADs have been developed in biocompatible, lightweight, bionic, and intelligent ways. In this review, we summarize the development history of VADs, focusing on the mechanism and application status of dVADs in detail, and further discuss the research progress and use of VADs in China. Full article

The objective of the study was to describe the frequency of acute myocardial injury (AMI) assessed by high-sensitivity cardiac troponin I (hs-cTnI) levels and to determine the possible initial risk factors (related to the characteristics of the patient, the disease, and the initial management) in a population of adult patients with early sepsis (within the first 72 h of diagnosis) in a single tertiary hospital center in western Mexico. For the inferential statistics, the proportions of the categorical dichotomous variables were compared using the chi-square test. In all analyses, p values less than 0.05 with a 95% confidence interval were considered significant. We included a total of 64 patients diagnosed with early sepsis, of whom 46 presented elevated hs-cTnI and were classified as having AMI. In our study, the frequency of AMI in patients with early sepsis was 71.87%, and no significant differences were found in all of the characteristics of patients with early sepsis with and without AMI, nor was any significant association found with any of the variables analyzed. In the population of western Mexico, the frequency of AMI in patients with early sepsis, assessed by hs-cTnI levels, is high and similar to that reported in other populations worldwide. Full article

Perioperative transient ischemic attacks (PTIAs) are associated with significantly increased rates of postoperative complications such as low cardiac output, atrial fibrillation, and significantly higher mortality in cardiac procedures. The current literature on PTIAs is sparse and understudied. Therefore, we aim to understand the effects of PTIA on hospital utilization, readmission, and morbidity. Using data on all the cardiac procedures at the University of Pittsburgh Medical Center from 2011 to 2019, fine and gray analysis was performed to identify whether PTIAs and covariables correlate with increased hospital utilization, stroke, all-cause readmission, Major Adverse Cardiac and Cerebrovascular Events (MACCE), MI, and all-cause mortality. Logistic regression for longer hospitalization showed that PTIA (HR: 2.199 [95% CI: 1.416–3.416] increased utilization rates. Fine and gray modeling indicated that PTIA (HR: 1.444 [95% CI: 1.096–1.902], p < 0.01) increased the rates of follow-up all-cause readmission. However, PTIA (HR: 1.643 [95% CI: 0.913–2.956] was not statistically significant for stroke readmission modeling. Multivariate modeling for MACCE events within 30 days of surgery (HR: 0.524 [95% CI: 0.171–1.605], p > 0.25) and anytime during the follow-up period (HR: 1.116 [95% CI: 0.825–1.509], p > 0.45) showed no significant correlation with PTIA. As a result of PTIA’s significant burden on the healthcare system due to increased utilization, it is critical to better define and recognize PTIA for timely management to improve perioperative outcomes. Full article

In patent ductus arteriosus (PDA) in preterm infants, the relationship between treatment timing and long-term developmental prognosis remains unclear. The purpose of this study was to clarify the relationship between the age in days when ductus arteriosus closure occurred and long-term development. Preterm infants with a birth weight of less than 1500 g who were admitted to our NICU over a period of 9 years (2011–2019) and were diagnosed with PDA were included. A new version of the K-type developmental test for corrected ages of 1.5 and 3 years was used as an index of development. The relationship between the duration of PDA and the developmental index was evaluated using Pearson’s correlation coefficient, and multiple regression analysis was performed. Development quotient (DQ) at the ages of 1.5 and 3 years showed a correlation with the PDA closure date and the standard deviation (SD) value of the term birth weight. Multiple regression analysis showed a positive correlation of the DQ at 1.5 and 3 years with the SD value of the term birth weight and a negative correlation with the PDA closure date. In addition, a stronger correlation was found in the “posture/motor” sub-item at 3 years. On the other hand, the analysis including preterm infants without PDA showed that preterm infants with PDA closure on the 6th day or later after birth had a significantly lower 3-year-old DQ than preterm infants with a PDA exposure within 5 days. In conclusion, it is suggested that the decrease in cerebral blood flow due to PDA in preterm infants has an adverse effect on long-term neurodevelopment. Appropriate interventions, including surgical treatment for PDA in preterm infants without delay, ideally within 5 days of birth, may be effective in improving the developmental prognosis. Full article

Background: The mechanisms underlying the impact of estradiol (E2) on low-density lipoprotein cholesterol (LDL-C) levels are not completely understood, although a role for proprotein convertase subtilisin/kexin type 9 (PCSK9) has been proposed. We aimed to investigate the association between levels of E2, PCSK9, and lipid parameters in premenopausal women undergoing in vitro fertilization (IVF). Methods: Healthy women undergoing IVF in the Department of Obstetrics and Gynecology of the University General Hospital of Ioannina were recruited. Their levels of E2, PCSK9, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), LDL-C, and triglycerides (TGs) were measured 10 days after ovarian depression (E2min) and 7 days after ovarian stimulation (E2max). Results: We included 34 consecutive women of median age 38 (interquartile range 26–46) years who underwent a full IVF cycle. As expected, E2 levels increased by 329.6% from E2min to E2max (108 [47–346] to 464 [241–2471] pg/mL, p < 0.05). During the same time, serum PCSK9 levels decreased by 30.8% (245 ± 80 to 170 ± 64 ng/mL, p < 0.05). TC, LDL-C, and TGs decreased by 0.4%, 3.8%, and 2.2%, respectively, while HDL-C levels increased by 5.3% (all p = NS). Conclusions: The rise in endogenous E2 during an IVF cycle was related with a significant decline in serum PCSK9 levels, but no significant change in plasma lipids during a 7-day period. Full article

Cardiac resynchronization therapy (CRT) is a recognized therapy for heart failure with altered ejection fraction and abnormal left ventricular activation time. Since the introduction of the therapy, a 30% rate of non-responders is observed and unchanged. The 12-lead ECG remains the only recommended tool for patient selection to CRT. The 12-lead ECG is, however, limited in its inability to provide a precise pattern of regional electrical activity. Electrocardiographic imaging (ECGi) provides a non-invasive detailed mapping of cardiac activation and therefore appears as a promising tool for CRT candidates. The non-invasive ventricular activation maps acquired by ECGi have been primarily explored for the diagnosis and guidance of therapy in patients with atrial or ventricular tachyarrhythmia. However, the accuracy of the system in this field is lacking and needs further improvement before considering a clinical application. On the other hand, its use for patient selection for CRT is encouraging. In this review, we introduce the technical considerations and we describe how ECGi can precisely characterize ventricular activation, especially in patients with left bundle branch block, thus identifying the electrical substrate responsive to CRT. Full article

Sinus of Valsalva aneurysms (SVAs) are infrequently seen in the pediatric population. When these aneurysms rupture, a significant hemodynamic burden is placed on the heart and increases the likelihood of cardiac failure. Here, we report a case of a ruptured SVA into the ventricular myocardium in a fetus with a form of double-inlet left ventricle. To the best of our knowledge, this has not previously been described. Full article

Cardiovascular CT is being widely used in the diagnosis of cardiovascular disease due to the rapid technological advancements in CT scanning techniques. These advancements include the development of multi-slice CT, from early generation to the latest models, which has the capability of acquiring images with high spatial and temporal resolution. The recent emergence of photon-counting CT has further enhanced CT performance in clinical applications, providing improved spatial and contrast resolution. CT-derived fractional flow reserve is superior to standard CT-based anatomical assessment for the detection of lesion-specific myocardial ischemia. CT-derived 3D-printed patient-specific models are also superior to standard CT, offering advantages in terms of educational value, surgical planning, and the simulation of cardiovascular disease treatment, as well as enhancing doctor–patient communication. Three-dimensional visualization tools including virtual reality, augmented reality, and mixed reality are further advancing the clinical value of cardiovascular CT in cardiovascular disease. With the widespread use of artificial intelligence, machine learning, and deep learning in cardiovascular disease, the diagnostic performance of cardiovascular CT has significantly improved, with promising results being presented in terms of both disease diagnosis and prediction. This review article provides an overview of the applications of cardiovascular CT, covering its performance from the perspective of its diagnostic value based on traditional lumen assessment to the identification of vulnerable lesions for the prediction of disease outcomes with the use of these advanced technologies. The limitations and future prospects of these technologies are also discussed. Full article

Background: This study considers care management for older chronic patients during and after the COVID-19 pandemic. Aims: To identify groups of variables at previous time points as a basis for deriving efficient classification models during and after a pandemic situation and to quantify the effect of each variable within the model to predict levels of worsening risk in diastolic and systolic arterial hypertension (AHT). Material and Methods: In this prospective longitudinal study, data were collected at three time points: before, during, and after the COVID-19 pandemic period. Results: The study included 148 patients with an average age of 81.6 years. During the study period, mean systolic blood pressure among this population rose by 5 mmHg to 128.8 mmHg; the number of patients with systolic blood pressure > 140 mmHg rose by 45.3%; among those with diastolic blood pressure > 90, the number rose by 41.2%; mean triglycerides levels rose to 152.6 mg/dL; cholesterol levels rose to 147 mg/dL; and LDL cholesterol rose to 112.2 mg/dL. Meanwhile, mean levels of HDL cholesterol decreased to 46.5 mg/dL. Binary-response logistic regression models were constructed to identify the most relevant variables for predicting AHT risk during and after the pandemic. The heart rate (OR = 1.79; 95% CI: 1.22–2.72) and body mass index (OR = 1.75; 95% CI: 1.08–2.94) variables were significant at the population level (p < 0.05) for diastolic and systolic AHT in the pandemic period risk models. The body mass index variable was also significant for diastolic AHT in the post-pandemic period risk model (OR = 1.97; 95% CI: 1.32–2.94), whilst the triglycerides variable was significant in the systolic AHT post-pandemic period risk model (OR = 1.49; 95% CI: 1.01–1.86). Conclusions: Bad control of arterial hypertension in older patients with chronic disease is associated with elevated levels of LDL cholesterol, total cholesterol, systolic blood pressure, heart rate and triglycerides, and lower levels of HDL cholesterol. Full article

Based mainly on their personal experience, the authors try to describe the origin of cardiovascular disease (CVD) epidemiology and the problems and difficulties practitioners attempted to tackle and solve during the first few decades of this discipline, which started around the middle of the last century. Beyond identifying the characteristics of those who became CVD epidemiologists, a description is given of the initial structures of the involved studies, participation rates, risk factors measurements and standardization, clinical measurements and diagnostic criteria, mortality data collection and coding, data loading and analysis, plus a number of problems still unsolved at the beginning of the 2000s. Despite many obstacles, and the initial hostility of the medical–scientific establishment, CVD epidemiology represented a revolution in researching in the bio-medical field. In the end, it also affected clinical research introducing the use of the quantitative approach bound to mathematical–statistical procedures. After decades of hard work and the development of a number of innovative tools, CVD epidemiology received its deserved recognition, eventually being accepted as a reputable and independent scientific discipline. Yet, in several countries, especially those from Southern Europe, an academic recognition of CVD epidemiology is still lacking. Full article

This review focuses on emerging risk factors for stroke, including air pollution and climate change, gut microbiota, high altitude, and systemic infection. Up to 14% of all stroke-associated mortality is attributed to air pollution and is more pronounced in developing countries. Fine particulate matter and other air pollutants contribute to an increased stroke risk, and this risk appears to increase with higher levels and duration of exposure. Short term air pollution exposure has also been reported to increase the stroke risk. The gut microbiota is a complex ecosystem of bacteria and other microorganisms that reside in the digestive system and affect multiple body systems. Disruptions in the gut microbiota may contribute to stroke development, possibly by promoting inflammation and atherosclerosis. High altitudes have been associated with erythrocytosis and cerebrovascular sinus thrombosis, but several studies have reported an increased risk of thrombosis and ischemic stroke at high altitudes, typically above 3000 m. Systemic infection, particularly infections caused by viruses and bacteria, can also increase the risk of stroke. The risk seems to be greatest in the days to weeks following the infection, and the pathophysiology is complex. All these emerging risk factors are modifiable, and interventions to address them could potentially reduce stroke incidence. Full article

Vectorcardiographic QRS area is a promising tool for patient selection and implantation guidance in cardiac resynchronization therapy (CRT). Research has mainly focused on the role of QRS area in patient selection for CRT. Recently, QRS area has been proposed as a tool to guide left ventricular lead placement in CRT. Theoretically, vector-based electrical information of ventricular fusion pacing, calculated from the basic 12-lead ECG, can give real-time insight into the extent of resynchronization at any LV lead position, as well as any selected electrode on the LV lead. The objective of this review is to provide an overview of the background of vectorcardiographic QRS area and its potential in optimizing LV lead location in order to optimize the benefits of CRT. Full article

Surgical repair for regurgitant bicuspid aortic valve (BAV) is promising but underutilized due to perceived complexities and lack of long-term data. This study evaluated the efficacy of valve-sparing root remodeling (VSRR) or isolated valve repair combined with calibrated external ring annuloplasty in BAV versus tricuspid aortic valve (TAV) patients. All patients operated on for aortic regurgitation and/or aneurysm at our institution between 2014 and 2022 were included and entered into the Aortic Valve Insufficiency and ascending aorta Aneurysm InternATiOnal Registry (AVIATOR). Patients with successful repair at index surgery (100% in the BAV group, 93% in the TAV group, p = 0.044) were included in a systemic follow-up with echocardiography at regular intervals. Among 132 patients, 58 were in the BAV (44%) and 74 in the TAV group (56%). There were no inter-group differences in preoperative patient characteristics, except BAV patients being significantly younger (47 ± 18 y vs. 60 ± 14 y, p < 0.001) and having narrower aortic roots at the level of sinuses (41 ± 6 mm vs. 46 ± 13 mm, p < 0.001) and sinotubular junctions (39 ± 10 mm vs. 42 ± 11, p = 0.032). No perioperative deaths were recorded. At four years, there was no significant difference in terms of overall survival (96.3% BAV vs. 97.2% TAV, p = 0.373), freedom from valve reintervention (85.2% BAV vs. 93.4% TAV, p = 0.905), and freedom from severe aortic regurgitation (94.1% BAV vs. 82.9% TAV, p = 0.222). Surgical repair of BAV combined with extra-aortic annuloplasty can be performed with low perioperative morbidity and mortality and excellent mid-term results which are comparable to TAV repair. Full article

(1) Background: Lung cancer screening (LCS) consists of low-dose computed tomography (LDCT) results to reduce lung cancer-related mortality. The LCS program has a unique opportunity to impact CVD mortality by providing tools for CVD risk assessment and implementing preventative strategies. In this study, we estimated standardized CVD risk (SCORE) and assessed the prevalence of coronary artery calcium (CAC) in a Polish LCS cohort. (2) Methods: In this observational study, 494 LCS participants aged 50–79 years with a cigarette smoking history of at least 30 pack-years were included. Medical history, anthropometric measurements, blood pressure measurements, serum glucose, and cholesterol levels were assessed in one visit. CVD risk assessment using SCORE tables was performed. The results were compared to the general population (NATPOL 2011 study). On LDCT scans, CAC was classified using an Ordinal Score ranging from 0 to 12. (3) Results: The prevalence of classic cardiovascular risk factors was very high. Among study participants, 83.7% of men and 40.7% of women were classified with a very high CVD SCORE risk (>10%). CAC was reported in 190 (47%) participants. Calcification was categorized as severe (CAC ≥ 4) in 84 (21%) participants. (4) Conclusions: Due to the high cardiovascular risk, intensive preventive strategies are recommended for LCS participants. Full article

Heart failure is a cardiovascular condition, leading to fatigue, breathlessness, and fluid retention. It affects around 56 million people globally and is a leading cause of hospitalization and mortality. Its prevalence is rising due to aging populations and lifestyle factors. Managing heart failure demands a multidisciplinary approach, encompassing medications, lifestyle modifications, and often medical devices or surgeries. The treatment burden is substantial, impacting patients’ daily lives and straining healthcare systems. Improving early detection, novel therapies, and patient education are crucial for alleviating the burden and enhancing the quality of life. There are notable advancements in the field of heart failure treatment and prevention. We will discuss significant pharmacological and device advances related to heart failure, including angiotensin receptor–neprilysin inhibitor, sodium–glucose co-transporter inhibition, glucagon-like peptide-1 agonist, cardiac resynchronization therapy, cardiac contractility modulation, mechanical circulatory support devices, and transcatheter valve interventions. We will also review novel therapies on the horizon, emerging technologies like CRISPR-based treatments for genetic anomalies, and the involvement of artificial intelligence in heart failure detection and management. Full article

Background: Quantitative flow ratio (QFR) virtual angioplasty with pre-PCI residual QFR showed better results compared with an angiographic approach to assess post-PCI functional results. However, correlation with pre-PCI residual QFR and post-PCI fractional flow reserve (FFR) is lacking. Methods: A multicenter prospective study including consecutive patients with angiographically 50–90% coronary lesions and positive QFR results. All patients were evaluated with QFR, hyperemic and non-hyperemic pressure ratios (NHPR) before and after the index PCI. Pre-PCI residual QFR (virtual angioplasty) was calculated and compared with post-PCI fractional flow reserve (FFR), QFR and NHPR. Results: A total of 84 patients with 92 treated coronary lesions were included, with a mean age of 65.5 ± 10.9 years and 59% of single vessel lesions being the left anterior descending artery in 69%. The mean vessel diameter was 2.82 ± 0.41 mm. Procedural success was achieved in all cases, with a mean number of implanted stents of 1.17 ± 0.46. The baseline QFR value was 0.69 ± 0.12 and baseline FFR and NHPR were 0.73 ± 0.08 and 0.82 ± 0.11, respectively. Mean post-PCI FFR increased to 0.87 ± 0.05 whereas residual QFR had been estimated as 0.95 ± 0.05, showing poor correlation with post-PCI FFR (0.163; 95% CI:0.078–0.386) and low diagnostic accuracy (30.9%, 95% CI:20–43%). Conclusions: In this analysis, the results of QFR-based virtual angioplasty did not seem to accurately correlate with post-PCI FFR. Full article

Cardioembolic strokes account for 20–25% of all ischaemic strokes, with their incidence increasing with age. Cardiac imaging plays a crucial role in identifying cardioembolic causes of stroke, with early and accurate identification affecting treatment, preventing recurrence, and reducing stroke incidence. Echocardiography serves as the mainstay of cardiac evaluation. Transthoracic echocardiography (TTE) is the first line in the basic evaluation of structural heart disorders, valvular disease, vegetations, and intraventricular thrombus. It can be used to measure chamber size and systolic/diastolic function. Trans-oesophageal echocardiography (TOE) yields better results in identifying potential cardioembolic sources of stroke and should be strongly considered, especially if TTE does not yield adequate results. Cardiac computed tomography and cardiac magnetic resonance imaging provide better soft tissue characterisation, high-grade anatomical information, spatial and temporal visualisation, and image reconstruction in multiple planes, especially with contrast. These techniques are useful in cases of inconclusive echocardiograms and can be used to detect and characterise valvular lesions, thrombi, fibrosis, cardiomyopathies, and aortic plaques. Nuclear imaging is not routinely used, but it can be used to assess left-ventricular perfusion, function, and dimensions and may be useful in cases of infective endocarditis. Its use should be considered on a case-by-case basis. The accuracy of each imaging modality depends on the likely source of cardioembolism, and the choice of imaging approach should be tailored to individual patients. Full article

Type 2 diabetes (T2D) is a multisystem disease with rapidly increasing global prevalence. Heart failure has emerged as a major complication of T2D. Dysregulated myocardial calcium handling is evident in the failing heart and this may be a key driver of cardiomyopathy in T2D, but until recently this has only been demonstrated in animal models. In this review, we describe the physiological concepts behind calcium handling within the cardiomyocyte and the application of novel imaging techniques for the quantification of myocardial calcium uptake. We take an in-depth look at the evidence for the impairment of calcium handling in T2D using pre-clinical models as well as in vivo studies, following which we discuss potential novel therapeutic approaches targeting dysregulated myocardial calcium handling in T2D. Full article

This article is the third in our series dedicated to the analysis of cardiac myoarchitecture as a nematic chiral liquid crystal (NCLC). Previously, we introduced the concept of topological defects (disclinations) and focused on their visual identification inside the compact myocardium. Herein, we investigate these using a mathematical and automated algorithm for the reproducible identification of a larger panel of topological defects throughout the myocardium of 13 perinatal and 11 early infant hearts. This algorithm identified an average of 29 ± 11 topological defects per slice with a 2D topological charge of m = +1/2 and an average of 27 ± 10 topological defects per slice with a 2D topological charge of m = −1/2. The excess of defects per slice with a 2D topological charge of m = +1/2 was statistically significant (p < 0.001). There was no significant difference in the distribution of defects with a 2D topological charge of m = +1/2 and m = −1/2 between perinatal and early infant hearts. These defects were mostly arranged in pairs, as expected in nematics, and located inside the trabecular myocardium. When isolated, defects with a 2D topological charge of m = +1/2 were located near the luminal extremity of the trabeculae and those with a 2D topological charge of m = −1/2 were located at the anterior and posterior part of the interventricular septum. These findings constitute an advance in the characterization of the deep cardiac myoarchitecture for application in developmental and pathological studies. Full article

Background: We aimed to determine if maximal oxygen uptake ($\dot{\mathrm{V}}$O₂max), resting heart rate (RHR), and self-reported leisure- time moderate to vigorous physical activity (MVPA) changed over a 3-year follow-up (FU) among industrial workers. Methods: We assessed cardiorespiratory fitness (CRF) August 2018 and August 2021. The last 17–18 months coincided with the COVID-19 pandemic. Data from 86 participants were collected; demographics by questionnaire and cardiovascular outcomes from medical examination: $\dot{\mathrm{V}}$O_2max, RHR, and fat mass (%). Workers reported on their leisure-time MVPA twice. To assess changes in health outcomes we applied a linear mixed model, adjusting for baseline (BL) age, sex, pack-years, shift work, and a 5-month plant shutdown. Further, we adjusted for actual age instead of BL age. Results: $\dot{\mathrm{V}}$O_2max decreased from 39.6 mL/kg/min at BL to 34.0 at FU, a reduction of 5.6 mL/kg/min (95%CI, −7.6, −3.7). Adjusted for actual age, the corresponding figure for $\dot{\mathrm{V}}$O_2max was 5.4 mL/kg/min, (95%CI, −7.4, −3.4), an annual loss of 4.6%. RHR increased from 61.3 to 64.4 beats per minute (95%CI, 0.8, 5.4). Self-reported MVPA decreased by 43.9 min/week, (95%CI, −73.5, −14.4). Conclusions: We observed a decrease in $\dot{\mathrm{V}}$O_2max, an increase in RHR and a decrease in self-reported MVPA, suggesting physical inactivity during the COVID-19 pandemic. Full article

Background: Phrenic nerve injury is a devastating complication that results in significant morbidity and mortality. We developed a novel technique to localize the phrenic nerve and evaluate its success. Methods: Two groups of children underwent repeat sternotomy for a variety of indications. Group I (69 patients, nerve stimulator) and Group II (78 patients, no nerve stimulator). Results: There was no significant difference in the mean age and weight between the two groups: (6.4 ± 6.5 years vs. 5.6 ± 6.4 years; p = 0.65) and (25.2 ± 24.1 vs. 22.6 ± 22.1; p = 0.69), respectively. The two groups were comparable in the following procedures: pulmonary conduit replacement, bidirectional cavopulmonary anastomosis, aortic arch repair, and Fontan, while Group I had more pulmonary arterial branch reconstruction (p = 0.009) and Group II had more heart transplant patients (p = 0.001). There was no phrenic nerve injury in Group I, while there were 13 patients who suffered phrenic nerve injury in Group II (p < 0.001). No early mortality in Group I, while five patients died prior to discharge in Group II. Eleven patients underwent diaphragm plication in Group II (p = 0.001). The mean number of hours on the ventilator was significantly higher in Group II (137.3 ± 324.9) compared to Group I (17 ± 66.9), p < 0.001. Group II had a significantly longer length of ICU and hospital stays compared to Group I (p = 0.007 and p = 0.006 respectively). Conclusion: Phrenic nerve injury in children continues to be associated with significant morbidities and increased length of stay. The use of intraoperative phrenic nerve stimulator can be an effective way to localize the phrenic nerve and avoid its injury. Full article

Little information is available on age-related electrocardiographic changes in patients with Noonan syndrome. This single-center study evaluated the electrocardiograms of patients with Noonan syndrome. We divided the patients (n = 112; electrocardiograms, 256) into four groups according to age: G1 (1 month–1 year), G2 (1–6 years), G3 (6–12 years), and G4 (>12 years). Typical Noonan syndrome-related electrocardiographic features such as left-axis deviation, abnormal Q wave, wide QRS complex, and small R wave in precordial leads were detected. A high percentage of QRS axis abnormalities was found in all groups. Significant differences in right-axis deviation (RAD) were noted among the groups: 56.5% of G1 patients showed RAD compared with 33.3% of G2, 21.1% of G3, and 19.2% of G4 patients. The small R was also significantly different among the groups: 32.6% of G1 patients showed a small R wave compared with 14.9% of G2, 8.5% of G3, and 15.4% of G4 patients. Of the 53 patients with Noonan syndrome aged 1 month to 2 years, 18 had T-positive V1 with a higher prevalence of pulmonary stenosis and cardiac interventions. QRS axis abnormalities, small R in V6, and T-positive V1 could help diagnose Noonan syndrome in infants or young children. Full article

There is no universal consensus on management of patent ductus arteriosus (PDA) in preterm infants and it varies significantly worldwide, even among the clinicians within units. The decision to treat requires a thorough understanding of the clinical status of the patient, clinical evaluation of PDA, echocardiographic diagnosis, and hemodynamic impact of ductal shunt on the pulmonary and systemic circulation. In this article, updated evidence on the efficacy and adverse effects of pharmacological treatment options and expectant management are presented, while highlighting the long-term benefits of PDA treatment remains equivocal and controversial. The authors propose a schematic targeted PDA treatment approach based on gestational and chronological age for practical clinical use, and they emphasize important future directions including advancement in PDA device closure techniques, diagnostic echo-parameters, hemodynamic evaluation to assess the impact on other organs, and understanding the long-term outcomes. Full article

Background: The endothelial cell layer is essential for the maintenance of various blood vessel functions. Major risk factors for endothelial dysfunction that contribute to aortic pathologies such as abdominal aortic aneurysm (AAA) and aortic dissection (AD) include smoking tobacco cigarettes and hypertension. This study explores the effects of nicotine (Nic) and angiotensin II (Ang II) on human aortic endothelial cells (HAoECs) at a transcriptional level. Methods: HAoECs were exposed to 100 nM Nic and/or 100 nM Ang II. RNA sequencing (RNA-Seq) was performed to identify regulated genes following exposure. Results were validated applying RT-qPCR. GeneMANIA was used to perform in silico analysis aiming to identify potential downstream interacting genes in inflammatory, cell-adhesion, endothelial cell proliferation, and coagulation pathways. Results: RNA-Seq identified LGALS9 (Galectin-9) as being potentially regulated following Nic exposure, while subsequent RT-qPCR experiments confirmed the transcriptional regulation (p < 0.05). Subsequent in silico analysis identified potential candidate genes for interacting with LGALS9 in different gene sets. Of the top 100 genes potentially interacting with LGALS9, 18 were inflammatory response genes, 28 were involved in cell adhesion, 2 in cell proliferation, and 6 in coagulation. Conclusion: Nic exposure of HAoECs causes a significant increase in LGALS9 at a transcriptional level. LGALS9 itself may serve as key regulator for essential endothelial cell processes via interfering with various signaling pathways and may thus represent a potentially novel target in the pathogenesis of aortic pathologies. Full article

Calciprotein particles (CPPs) are indispensable scavengers of excessive Ca²⁺ and PO₄³⁻ ions in blood, being internalised and recycled by liver and spleen macrophages, monocytes, and endothelial cells (ECs). Here, we performed a pathway enrichment analysis of cellular compartment-specific proteomes in primary human coronary artery ECs (HCAEC) and human internal thoracic artery ECs (HITAEC) treated with primary (amorphous) or secondary (crystalline) CPPs (CPP-P and CPPs, respectively). Exposure to CPP-P and CPP-S induced notable upregulation of: (1) cytokine- and chemokine-mediated signaling, Ca²⁺-dependent events, and apoptosis in cytosolic and nuclear proteomes; (2) H⁺ and Ca²⁺ transmembrane transport, generation of reactive oxygen species, mitochondrial outer membrane permeabilisation, and intrinsic apoptosis in the mitochondrial proteome; (3) oxidative, calcium, and endoplasmic reticulum (ER) stress, unfolded protein binding, and apoptosis in the ER proteome. In contrast, transcription, post-transcriptional regulation, translation, cell cycle, and cell–cell adhesion pathways were underrepresented in cytosol and nuclear compartments, whilst biosynthesis of amino acids, mitochondrial translation, fatty acid oxidation, pyruvate dehydrogenase activity, and energy generation were downregulated in the mitochondrial proteome of CPP-treated ECs. Differentially expressed organelle-specific pathways were coherent in HCAEC and HITAEC and between ECs treated with CPP-P or CPP-S. Proteomic analysis of mitochondrial and nuclear lysates from CPP-treated ECs confirmed bioinformatic filtration findings. Full article

Transcatheter aortic valve implantation (TAVI) has been established as a safe and efficacious treatment for patients with severe symptomatic aortic stenosis (AS). Despite being initially developed and indicated for high-surgical-risk patients, it is now offered to low-risk populations based on the results of large randomized controlled trials. The most common access sites in the vast majority of patients undergoing TAVI are the common femoral arteries; however, 10–20% of the patients treated with TAVI require an alternative access route, mainly due to peripheral atherosclerotic disease or complex anatomy. Hence, to achieve successful delivery and implantation of the valve, several arterial approaches have been studied, including transcarotid (TCr), axillary/subclavian (A/Sc), transapical (TAp), transaortic (TAo), suprasternal-brachiocephalic (S-B), and transcaval (TCv). This review aims to concisely summarize the most recent literature data and current guidelines as well as evaluate the various access routes for TAVI, focusing on the indications, the various special patient groups, and the advantages and disadvantages of each technique, as well as their adverse events. Full article