J. Cardiovasc. Dev. Dis., Volume 10, Issue 5 (May 2023) – 41 articles

Objective: The goal of this manuscript is to compare clinical and echocardiographic outcomes of patients undergoing aortic valve replacement (AVR) with Perceval sutureless bioprosthesis (SU-AVR) and sutured bioprosthesis (SB). Methods: Following the PRISMA statement, data were extracted from studies published after August 2022 and found in PubMed/MEDLINE, EMBASE, CENTRAL/CCTR, ClinicalTrials.gov, SciELO, LILACS, and Google Scholar. The primary outcome of interest was post-procedural permanent pacemaker implantation, and the secondary outcomes were new left bundle branch block (LBBB), moderate/severe paravalvular leak (PVL), valve dislocation (pop-out), need for a second transcatheter heart valve, 30-day mortality, stroke, and echocardiographic outcomes. Results: Twenty-one studies were included in the analysis. When SU-AVR was compared to other SB, mortality ranged from 0 to 6.4% for Perceval and 0 to 5.9% for SB. Incidence of PVL (Perceval 1–19.4% vs. SB 0–1%), PPI (Perceval 2–10.7% vs. SB 1.8–8.5%), and MI (Perceval 0–7.8% vs. SB 0–4.3%) were comparable. In addition, the stroke rate was lower in the SU-AVR group when compared to SB (Perceval 0–3.7% vs. SB 1.8–7.3%). In patients with a bicuspid aortic valve, the mortality rate was 0–4% and PVL incidence was 0–2.3%. Long-term survival ranged between 96.7 and 98.6%. Valve cost analysis was lower for the Perceval valve and higher for sutured bioprosthesis. Conclusions: Compared to SB valves, Perceval bioprosthesis has proved to be a reliable prosthesis for surgical aortic valve replacement due to its non-inferior hemodynamics, implantation speed, reduced cardiopulmonary bypass time, reduced aortic cross-clamp time, and shorter length of stay. Full article

Transcatheter aortic valve implantation (TAVI) was first presented in 2002 as a case report. Randomized controlled trials showed that TAVI could serve as an alternative for surgical aortic valve replacement (SAVR) in high-risk patients. While the indications for TAVI have expanded into low-risk groups, favorable results of SAVR in elderly showed an increase in application of surgical treatment in this age category. This review aims to explore the effect of the introduction of TAVI in the referral for SAVR with respect to volume, patient profile, early outcome, and use of mechanical heart valves. Results show that the volume of SAVR has increased in several cardiac centers. In a small minority of series, age and risk score of the referred patients also increased. In most of the series, early mortality rate reduced. These findings, however are not universal. Different management policies could be responsible for this observation. Moreover, some patients in whom aortic valve replacement in whatever form is indicated still do not receive adequate treatment. This can be due to several reasons. Heart teams consisting of interventional cardiologists and cardiac surgeons should become a universal approach in order to minimize the number of untreated patients. Full article

Introduction: The COVID-19 pandemic and consequent social isolation prompted a surge in mental health disorders and substance use in the general population and, therefore, in potential organ donors. We aimed to evaluate if this led to a change in donor characteristics, including the mechanism and circumstance of death, and how this may have affected clinical outcomes following heart transplantation. Methods: We identified all heart donors from the SRTR database between 18 October 2018 and 31 December 2021, excluding those who donated immediately after the US national emergency declaration. Donors were stratified into pre-COVID-19 (Pre-Cov; through 12 March 2020) and post-COVID-19 national emergency declaration cohorts (Post-Cov; 1 August 2020 through 31 December 2021) based on the heart procurement date. Relevant demographics, cause of death, and substance use history were collected in addition to graft cold ischemic time, the incidence of primary graft dysfunction (PGD), and recipient survival at 30 days post-transplant. Results: A total of 10,314 heart donors were identified; 4941 were stratified into the Pre-Cov and 5373 into the Post-Cov cohorts. There was no difference in demographics, but illicit drug use was significantly higher in the Post-Cov group, leading to an increased incidence of death from drug intoxication. Fatal gunshot wounds were also more common. Despite these changes, the incidence of PGD remained similar (p = 0.371), and there was no difference in 30 days recipient survival (p = 0.545). Conclusion: Our findings confirm that COVID-19 had a major impact on mental health and psychosocial life with an associated increase in illicit substance use and fatal intoxication rates in heart transplant donors. These changes did not alter peri-operative mortality following heart transplantation. Future studies are needed to ensure that long-term outcomes remain unaffected. Full article

The PAF1 complex component Rtf1 is an RNA Polymerase II-interacting transcription regulatory protein that promotes transcription elongation and the co-transcriptional monoubiquitination of histone 2B. Rtf1 plays an essential role in the specification of cardiac progenitors from the lateral plate mesoderm during early embryogenesis, but its requirement in mature cardiac cells is unknown. Here, we investigate the importance of Rtf1 in neonatal and adult cardiomyocytes using knockdown and knockout approaches. We demonstrate that loss of Rtf1 activity in neonatal cardiomyocytes disrupts cell morphology and results in a breakdown of sarcomeres. Similarly, Rtf1 ablation in mature cardiomyocytes of the adult mouse heart leads to myofibril disorganization, disrupted cell–cell junctions, fibrosis, and systolic dysfunction. Rtf1 knockout hearts eventually fail and exhibit structural and gene expression defects resembling dilated cardiomyopathy. Intriguingly, we observed that loss of Rtf1 activity causes a rapid change in the expression of key cardiac structural and functional genes in both neonatal and adult cardiomyocytes, suggesting that Rtf1 is continuously required to support expression of the cardiac gene program. Full article

Imaging modalities are increasingly being used to evaluate the underlying pathophysiology of heart failure. Positron emission tomography (PET) is a non-invasive imaging technique that uses radioactive tracers to visualize and measure biological processes in vivo. PET imaging of the heart uses different radiopharmaceuticals to provide information on myocardial metabolism, perfusion, inflammation, fibrosis, and sympathetic nervous system activity, which are all important contributors to the development and progression of heart failure. This narrative review provides an overview of the use of PET imaging in heart failure, highlighting the different PET tracers and modalities, and discussing fields of present and future clinical application. Full article

Background: A progressively increasing prevalence of congenital heart disease (CHD) in adulthood has been noticed in recent decades; CHD cases with a systemic right ventricle have a poorer outcome. Methods: Seventy-three patients with SRV evaluated in an outpatient clinic between 2014 and 2020 were enrolled in this study. Thirty-four patients had a transposition of the great arteries treated with an atrial switch operation; 39 patients had a congenitally corrected transposition of the great arteries (ccTGA). Results: Mean age at the first evaluation was 29.6 ± 14.2 years; 48% of the patients were female. The NYHA class at the visit was III or IV in 14% of the cases. Thirteen patients had at least one previous pregnancy. In 25% of the cases, complications occurred during pregnancy. Survival free from adverse events was 98.6% at one year and 90% at 6-year follow-up without any difference between the two groups. Two patients died and one received heart transplantation during follow-up. The most common adverse event during follow-up was the presence of arrhythmia requiring hospitalization (27.1%), followed by heart failure (12.3%). The presence of LGE together with lower exercise capacity, higher NYHA class and more dilated and/or hypokinetic RV predicted a poorer outcome. Quality of life was similar to the QoL of the Italian population. Conclusions: Long-term follow-up of patients with a systemic right ventricle is characterized by a high incidence of clinical events, prevalently arrhythmias and heart failure, which cause most of the unscheduled hospitalizations. Full article

Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice, and it is an enormous burden worldwide because of its high morbidity, disability and mortality. It is generally acknowledged that physical activity (PA) is strongly associated with a significant reduction in the risk of cardiovascular (CV) disease and all-cause mortality. Moreover, it has been observed that moderate and regular physical activity has the potential to reduce the risk of AF, in addition to improving overall well-being. Nevertheless, some studies have associated intense physical activity with an increased risk of AF. This paper aims to review the main related literature to investigate the association between PA and AF incidence and draw pathophysiological and epidemiological conclusions. Full article

Background: Understanding and effectively treating dystrophin-deficient cardiomyopathy is of high importance for Duchenne muscular dystrophy (DMD) patients due to their prolonged lifespan. We used two-dimensional speckle tracking echocardiography to analyze more deeply the non-uniformity of myocardial strain within the left ventricle during the progression of cardiomyopathy in golden retriever muscular dystrophy (GRMD) dogs. Methods: The circumferential strain (CS) and longitudinal strain (LS) of left ventricular (LV) endocardial, middle and epicardial layers were analyzed from three parasternal short-axis views and three apical views, respectively, in GRMD (n = 22) and healthy control dogs (n = 7) from 2 to 24 months of age. Results: In GRMD dogs, despite normal global systolic function (normal LV fractional shortening and ejection fraction), a reduction in systolic CS was detected in the three layers of the LV apex but not in the LV middle-chamber and base at 2 months of age. This spatial heterogeneity in CS progressed with age, whereas a decrease in systolic LS could be detected early at 2 months of age in the three layers of the LV wall from three apical views. Conclusions: Analyzing the evolution of myocardial CS and LS in GRMD dogs reveals spatial and temporal non-uniform alterations of LV myocardial strain, providing new insights into the progression of dystrophin-deficient cardiomyopathy in this relevant model of DMD. Full article

Aortic stenosis is the most common form of valve disease in the Western world and a major healthcare burden. Although echocardiography remains the central modality for the diagnosis and assessment of aortic stenosis, recently, advanced cardiac imaging with cardiovascular magnetic resonance, computed tomography, and positron emission tomography have provided invaluable pathological insights that may guide the personalized management of the disease. In this review, we discuss applications of these novel non-invasive imaging modalities for establishing the diagnosis, monitoring disease progression, and eventually planning the invasive treatment of aortic stenosis. Full article

Hypoxia-inducible factors (HIFs) play a crucial role in cellular responses to low oxygen levels during myocardial ischemia and reperfusion injury. HIF stabilizers, originally developed for treating renal anemia, may offer cardiac protection in this context. This narrative review examines the molecular mechanisms governing HIF activation and function, as well as the pathways involved in cell protection. Furthermore, we analyze the distinct cellular roles of HIFs in myocardial ischemia and reperfusion. We also explore potential therapies targeting HIFs, emphasizing their possible benefits and limitations. Finally, we discuss the challenges and opportunities in this research area, underscoring the need for continued investigation to fully realize the therapeutic potential of HIF modulation in managing this complex condition. Full article

Remote monitoring (RM) is the newest function of cardiac implantable electronic devices (CIEDs). In our observational retrospective analysis, we aimed to assess whether telecardiology could be a safe alternative to routine outpatient examinations during the COVID-19 pandemic. The in- and outpatient visits, the number of acute cardiac decompensation episodes, the RM data from CIEDs, and general condition were examined via questionnaires (KCCQ, EQ-5D-5L). Regarding the enrolled 85 patients, the number of personal patient appearances was significantly lower in the year following the pandemic outbreak compared to the previous year (1.4 ± 1.4 and 1.9 ± 1.2, p = 0.0077). The number of acute decompensation events was five before and seven during lockdown (p = 0.6). Based on the RM data, there was no significant difference in heart failure (HF) markers (all related p > 0.05); only patient activity increased after restrictions were lifted compared to that before the lockdown (p = 0.03). During restrictions, patients reported increased anxiety and depression compared to their previous state (p < 0.001). There was no subjective change in the perception of HF symptoms (p = 0.7). Based on the subjective perception and CIED data, the quality of life of patients with CIED did not deteriorate during the pandemic, but their anxiety and depression intensified. Telecardiology may be a safe alternative to routine inpatient examination. Full article

Cardiac surgery is one of the highest-risk procedures, usually involving cardiopulmonary bypass and commonly inducing endothelial injury that contributes to the development of perioperative and postoperative organ dysfunction. Substantial scientific efforts are being made to unravel the complex interaction of biomolecules involved in endothelial dysfunction to find new therapeutic targets and biomarkers and to develop therapeutic strategies to protect and restore the endothelium. This review highlights the current state-of-the-art knowledge on the structure and function of the endothelial glycocalyx and mechanisms of endothelial glycocalyx shedding in cardiac surgery. Particular emphasis is placed on potential strategies to protect and restore the endothelial glycocalyx in cardiac surgery. In addition, we have summarized and elaborated the latest evidence on conventional and potential biomarkers of endothelial dysfunction to provide a comprehensive synthesis of crucial mechanisms of endothelial dysfunction in patients undergoing cardiac surgery, and to highlight their clinical implications. Full article

Background: Frailty is highly common in older patients (pts) undergoing transcatheter aortic valve replacement (TAVR), and it is associated with poor outcomes. The selection of patients who can benefit from this procedure is necessary and challenging. The aim of the present study is to evaluate outcomes in older severe aortic valve stenosis (AS) pts, selected by a multidisciplinary approach for surgical, clinical, and geriatric risk and referred to treatment, according to frailty levels. Methods: A total of 109 pts (83 ± 5 years; females, 68%) with AS were classified by Fried’s score in pre-frail, early frail, and frail and underwent surgical aortic valve replacement SAVR/TAVR, balloon aortic valvuloplasty, or medical therapy. We evaluated geriatric, clinical, and surgical features and detected periprocedural complications. The outcome was all-cause mortality. Results: Increasing frailty was associated with the worst clinical, surgical, geriatric conditions. By using Kaplan–Meier analysis, the survival rate was higher in pre-frail and TAVR groups (p < 0.001) (median follow-up = 20 months). By using the Cox regression model, frailty (p = 0.004), heart failure (p = 0.007), EF% (p = 0.043), albumin (p = 0.018) were associated with all-cause mortality. Conclusions: According to tailored frailty management, elderly AS pts with early frailty levels seem to be the most suitable candidates for TAVR/SAVR for positive outcomes because advanced frailty would make each treatment futile or palliative. Full article

The Wilms tumor suppressor gene (Wt1) encodes a C2H2-type zinc-finger transcription factor that participates in transcriptional regulation, RNA metabolism, and protein–protein interactions. WT1 is involved in the development of several organs, including the kidneys and gonads, heart, spleen, adrenal glands, liver, diaphragm, and neuronal system. We previously provided evidence of transient WT1 expression in about 25% of cardiomyocytes of mouse embryos. Conditional deletion of Wt1 in the cardiac troponin T lineage caused abnormal cardiac development. A low expression of WT1 has also been reported in adult cardiomyocytes. Therefore, we aimed to explore its function in cardiac homeostasis and in the response to pharmacologically induced damage. Silencing of Wt1 in cultured neonatal murine cardiomyocytes provoked alterations in mitochondrial membrane potential and changes in the expression of genes related to calcium homeostasis. Ablation of WT1 in adult cardiomyocytes by crossing αMHC^MerCreMer mice with homozygous WT1-floxed mice induced hypertrophy, interstitial fibrosis, altered metabolism, and mitochondrial dysfunction. In addition, conditional deletion of WT1 in adult cardiomyocytes increased doxorubicin-induced damage. These findings suggest a novel role of WT1 in myocardial physiology and protection against damage. Full article

Atherosclerosis is a multifactorial systemic disease that affects the entire arterial tree, although some areas are more prone to lipid deposits than others. Moreover, the histopathological composition of the plaques differs, and the clinical manifestations are also different, depending on the location and structure of the atherosclerotic plaque. Some arterial systems are correlated with each other more than in that they simply share a common atherosclerotic risk. The aim of this perspective review is to discuss this heterogeneity of atherosclerotic impairment in different arterial districts and to investigate the current evidence that resulted from studies of the topographical interrelations of atherosclerosis. Full article

Among the most common problems facing public health today is a lack of vitamin D, which plays a role in the physiological processes of chronic illness conditions. Vitamin D deficiency in metabolic disorders has primary effects on osteoporosis, obesity, hypertension, diabetes, and cardiovascular disease (CVD). Vitamin D acts as a “co-hormone” in the various tissues of the body, and it has been found that vitamin D receptors (VDR) are present on all cell types, suggesting that vitamin D has a wide range of effects on most cells. Recently, there has been a surge in interest in assessing its roles. Vitamin D insufficiency increases the risk of diabetes because it lowers insulin sensitivity, and also raises the risk of obesity and CVD because of its effect on the body’s lipid profile, particularly in terms of the prevalence of dangerously high levels of low-density lipoproteins (LDL). Furthermore, vitamin D insufficiency is often related to CVD and connected risk factors, highlighting the need to know vitamin D’s functions in relation to metabolic syndrome and related processes. Through looking at previous studies, this paper explains why vitamin D is important, how deficiency is related to risk factors for metabolic syndrome through different mechanisms, and how deficiency affects CVD. Full article

Shock is a life-threatening condition, and its timely recognition is essential for adequate management. Pediatric patients with congenital heart disease admitted to a cardiac intensive care unit (CICU) after surgical corrections are particularly at risk of low cardiac output syndrome (LCOS) and shock. Blood lactate levels and venous oxygen saturation (ScVO₂) are usually used as shock biomarkers to monitor the efficacy of resuscitation efforts, but they are plagued by some limitations. Carbon dioxide (CO₂)-derived parameters, namely veno-arterial CO₂ difference (ΔCCO₂) and the VCO₂/VO₂ ratio, may represent a potentially valuable addition as sensitive biomarkers to assess tissue perfusion and cellular oxygenation and may represent a valuable addition in shock monitoring. These variables have been mostly studied in the adult population, with a strong association between ΔCCO₂ or VCO₂/VO₂ ratio and mortality. In children, particularly in CICU, few studies looked at these parameters, while they reported promising results on the use of CO₂-derived indices for patients’ management after cardiac surgeries. This review focuses on the physiological and pathophysiological determinants of ΔCCO₂ and VCO₂/VO₂ ratio while summarizing the actual state of knowledge on the use of CO₂-derived indices as hemodynamical markers in CICU. Full article

The global prevalence of chronic kidney disease (CKD) has increased in recent years. Adverse cardiovascular events have become the main cause of life-threatening events in patients with CKD, and vascular calcification is a risk factor for cardiovascular disease. Vascular calcification, especially coronary artery calcification, is more prevalent, severe, rapidly progressive, and harmful in patients with CKD. Some features and risk factors are unique to vascular calcification in patients with CKD; the formation of vascular calcification is not only influenced by the phenotypic transformation of vascular smooth muscle cells, but also by electrolyte and endocrine dysfunction, uremic toxin accumulation, and other novel factors. The study on the mechanism of vascular calcification in patients with renal insufficiency can provide a basis and new target for the prevention and treatment of this disease. This review aims to illustrate the impact of CKD on vascular calcification and to discuss the recent research data on the pathogenesis and factors involved in vascular calcification, mainly focusing on coronary artery calcification, in patients with CKD. Full article

Progress towards the development and adoption of minimally invasive techniques in cardiac surgery has been slower than that seen in other surgical specialties. Congenital heart disease (CHD) patients represent an important population within cardiac disease, of which atrial septal defect (ASD) is one of the most common diagnoses. Management of ASD encompasses a range of minimal-access and minimally invasive approaches, including transcatheter device closure, mini-sternotomy, thoracotomy, video-assisted, endoscopic, and robotic approaches. In this article, we will discuss the pathophysiology of ASD, along with diagnosis, management, and indications for intervention. We will review the current evidence supporting minimally invasive and minimal-access surgical ASD closure in the adult and paediatric patient, highlighting peri-operative considerations and areas for further research. Full article

The heart is capable of extensive adaptive growth in response to the demands of the body. When the heart is confronted with an increased workload over a prolonged period, it tends to cope with the situation by increasing its muscle mass. The adaptive growth response of the cardiac muscle changes significantly during phylogenetic and ontogenetic development. Cold-blooded animals maintain the ability for cardiomyocyte proliferation even in adults. On the other hand, the extent of proliferation during ontogenetic development in warm-blooded species shows significant temporal limitations: whereas fetal and neonatal cardiac myocytes express proliferative potential (hyperplasia), after birth proliferation declines and the heart grows almost exclusively by hypertrophy. It is, therefore, understandable that the regulation of the cardiac growth response to the increased workload also differs significantly during development. The pressure overload (aortic constriction) induced in animals before the switch from hyperplastic to hypertrophic growth leads to a specific type of left ventricular hypertrophy which, in contrast with the same stimulus applied in adulthood, is characterized by hyperplasia of cardiomyocytes, capillary angiogenesis and biogenesis of collagenous structures, proportional to the growth of myocytes. These studies suggest that timing may be of crucial importance in neonatal cardiac interventions in humans: early definitive repairs of selected congenital heart disease may be more beneficial for the long-term results of surgical treatment. Full article

Background: The guideline-recommended low-density lipoprotein cholesterol target level of <70 mg/dL may not be achieved with statin administration in some patients with acute coronary syndrome (ACS). Therefore, the proprotein convertase subtilisin-kexin type 9 (PCSK9) antibody can be added to high-risk patients with ACS. Nevertheless, the optimal duration of PCSK9 antibody administration remains unclear. Methods and Results: Patients were randomized to receive either 3 months of lipid lowering therapy (LLT) with the PCSK9 antibody followed by conventional LLT (with-PCSK9-antibody group) or 12 months of conventional LLT alone (without-PCSK9-antibody group). The primary endpoint was the composite of all-cause death, myocardial infarction, stroke, unstable angina, and ischemia-driven revascularization. A total of 124 patients treated with percutaneous coronary intervention (PCI) were randomly assigned to the two groups (n = 62 in each). The primary composite outcome occurred in 9.7% and 14.5% of the patients in the with- and without-PCSK9-antibody groups, respectively (hazard ratio: 0.70; 95% confidence interval: 0.25 to 1.97; p = 0.498). The two groups showed no significant differences in hospitalization for worsening heart failure and adverse events. Conclusions: In ACS patients who underwent PCI, short-term PCSK9 antibody therapy with conventional LLT was feasible in this pilot clinical trial. Long-term follow-up in a larger scale clinical trial is warranted. Full article

Background: Our aim was to determine the impact that metabolic syndrome (MS) produces in long-term heart rate variability (HRV), quantitatively synthesizing the results of published studies to characterize the cardiac autonomic dysfunction in MS. Methods: We searched electronic databases for original research works with long-term HRV recordings (24 h) that compared people with MS (MS+) versus healthy people as a control group (MS−). This systematic review and meta-analysis (MA) was performed according to PRISMA guidelines and registered at PROSPERO (CRD42022358975). Results: A total of 13 articles were included in the qualitative synthesis, and 7 of them met the required criteria to be included in the MA. SDNN (−0.33 [−0.57, 0.09], p = 0.008), LF (−0.32 [−0.41, −0.23], p < 0.00001), VLF (−0.21 [−0.31, −0.10], p = 0.0001) and TP (−0.20 [−0.33, −0.07], p = 0.002) decreased in patients with MS. The rMSSD (p = 0.41), HF (p = 0.06) and LF/HF ratio (p = 0.64) were not modified. Conclusions: In long-term recordings (24 h), SDNN, LF, VLF and TP were consistently decreased in patients with MS. Other parameters that could be included in the quantitative analysis were not modified in MS+ patients (rMSSD, HF, ratio LF/HF). Regarding non-linear analyses, the results are not conclusive due to the low number of datasets found, which prevented us from conducting an MA. Full article

As the world produces exabytes of data, there is a growing need to find new methods that are more suitable for dealing with complex datasets. Artificial intelligence (AI) has significant potential to impact the healthcare industry, which is already on the road to change with the digital transformation of vast quantities of information. The implementation of AI has already achieved success in the domains of molecular chemistry and drug discoveries. The reduction in costs and in the time needed for experiments to predict the pharmacological activities of new molecules is a milestone in science. These successful applications of AI algorithms provide hope for a revolution in healthcare systems. A significant part of artificial intelligence is machine learning (ML), of which there are three main types—supervised learning, unsupervised learning, and reinforcement learning. In this review, the full scope of the AI workflow is presented, with explanations of the most-often-used ML algorithms and descriptions of performance metrics for both regression and classification. A brief introduction to explainable artificial intelligence (XAI) is provided, with examples of technologies that have developed for XAI. We review important AI implementations in cardiology for supervised, unsupervised, and reinforcement learning and natural language processing, emphasizing the used algorithm. Finally, we discuss the need to establish legal, ethical, and methodical requirements for the deployment of AI models in medicine. Full article

Objectives. To investigate mortalities from three major groups of cardiovascular diseases (CVDs) in a pooled cohort and followed up until extinction. Materials and Methods. Ten cohorts of men (N = 9063) initially aged 40–59, in six countries, were examined and followed-up for 60 years. The major CVD groups were coronary heart disease (CHD), cerebrovascular diseases (STROKE) and other heart diseases of uncertain etiology (HDUE). Results. Death rates from CHD were higher in countries with high serum cholesterol levels (USA, Finland and The Netherlands) and lower in countries with low cholesterol levels (Italy, Greece and Japan), but the opposite was observed for STROKE and HDUE, which became the most common CVD mortalities in all countries during the last 20 years of follow-up. Systolic blood pressure and smoking habits were, at an individual level, the common risk factors for the three groups of CVD conditions, while serum cholesterol level was the most common risk factor only for CHD. Overall, death rates for the pooled CVDs were 18% higher in North American and Northern European countries, while CHD rates were 57% higher in the same countries. Conclusions. Differences in lifelong CVD mortalities across different countries were smaller than expected due to the different rates of the three groups of CVD, and the indirect determinant of this seemed to be baseline serum cholesterol levels. Full article

Sudden cardiac death (SCD) represents approximately 50% of all cardiovascular mortality in the United States. The majority of SCD occurs in individuals with structural heart disease; however, around 5% of individuals have no identifiable cause on autopsy. This proportion is even higher in those <40 years old, where SCD is particularly devastating. Ventricular fibrillation (VF) is often the terminal rhythm leading to SCD. Catheter ablation for VF has emerged as an effective tool to alter the natural history of this disease among high-risk individuals. Important advances have been made in the identification of several mechanisms involved in the initiation and maintenance of VF. Targeting the triggers of VF as well as the underlying substrate that perpetuates these lethal arrhythmias has the potential to eliminate further episodes. Although important gaps remain in our understanding of VF, catheter ablation has become an important option for individuals with refractory arrhythmias. This review outlines a contemporary approach to the mapping and ablation of VF in the structurally normal heart, specifically focusing on the following major conditions: idiopathic ventricular fibrillation, short-coupled ventricular fibrillation, and the J-wave syndromes—Brugada syndrome and early-repolarization syndrome. Full article

Introduction: The COVID-19 pandemic has changed the immunological status of the population, indicating increased activation. The aim of the study was to compare the degree of inflammatory activation in patients admitted for surgical revascularization in the period before and during the COVID-19 pandemic. Materials and methods: This retrospective analysis included an analysis of inflammatory activation assessed on the basis of whole blood counts in 533 patients (435 (82%) male and 98 (18%) female) with a median age of 66 (61–71) years who underwent surgical revascularization, including 343 and 190 patients operated on in 2018 and 2022, respectively. Results: The compared groups were matched by propensity score matching analysis, obtaining 190 patients in each group. Significantly higher values of preoperative monocyte count (p = 0.015), monocyte-to-lymphocyte ratio (p = 0.004) and systemic inflammatory response index (p = 0.022) were found in the during-COVID subgroup. The perioperative and 12-month mortality rates were comparable, with 1% (n = 4) in 2018 vs. 1% (n = 2) in 2022 (p = 0.911), and 5.6 % (n = 11 patients) vs. 7% (n = 13 patients) (p = 0.413), in the pre-COVID and during-COVID subgroups, respectively. Conclusions: Simple whole blood analysis in patients with complex coronary artery disease performed before and during the COVID-19 pandemic indicates excessive inflammatory activation. However, the immune variation did not interfere with one-year mortality rate after surgical revascularization. Full article

Background: digital variance angiography (DVA) provides higher image quality than digital subtraction angiography (DSA). This study investigates whether the quality reserve of DVA allows for radiation dose reduction during lower limb angiography (LLA), and compares the performance of two DVA algorithms. Methods: this prospective block-randomized controlled study enrolled 114 peripheral arterial disease patients undergoing LLA into normal dose (ND, 1.2 µGy/frame, n = 57) or low-dose (LD, 0.36 µGy/frame, n = 57) groups. DSA images were generated in both groups, DVA1 and DVA2 images were generated in the LD group. Total and DSA-related radiation dose area product (DAP) were analyzed. Image quality was assessed on a 5-grade Likert scale by six readers. Results: the total and DSA-related DAP were reduced by 38% and 61% in the LD group. The overall visual evaluation scores (median (IQR)) of LD-DSA (3.50 (1.17)) were significantly lower than the ND-DSA scores (3.83 (1.00), p < 0.001). There was no difference between ND-DSA and LD-DVA1 (3.83 (1.17)), but the LD-DVA2 scores were significantly higher (4.00 (0.83), p < 0.01). The difference between LD-DVA2 and LD-DVA1 was also significant (p < 0.001). Conclusions: DVA significantly reduced the total and DSA-related radiation dose in LLA, without affecting the image quality. LD-DVA2 images outperformed LD-DVA1, therefore DVA2 might be especially beneficial in lower limb interventions. Full article

Introduction: Persistent coronary microcirculatory dysfunction (CMD) and elevated trimethylamine N-oxide (TMAO) levels after ST-elevation myocardial infarction (STEMI) may drive negative structural and electrical cardiac remodeling, resulting in new-onset atrial fibrillation (AF) and a decrease in left ventricular ejection fraction (LVEF). Aims: TMAO and CMD are investigated as potential predictors of new-onset AF and left ventricular remodeling following STEMI. Methods: This prospective study included STEMI patients who had primary percutaneous coronary intervention (PCI) followed by staged PCI three months later. Cardiac ultrasound images were obtained at baseline and after 12 months to assess LVEF. Coronary flow reserve (CFR), and index of microvascular resistance (IMR) were assessed using the coronary pressure wire during the staged PCI. Microcirculatory dysfunction was defined as having an IMR value ≥25 U and CFR value <2.5 U. Results: A total of 200 patients were included in the study. Patients were categorized according to whether or not they had CMD. Neither group differed from the other with regards to known risk factors. Despite making up only 40.5% of the study population, females represented 67.4% of the CMD group p < 0.001. Similarly, CMD patients had a much higher prevalence of diabetes than those without CMD (45.7% vs. 18.2%; p < 0.001). At the one-year follow-up, the LVEF in the CMD group had decreased to significantly lower levels than those in the non-CMD group (40% vs. 50%; p < 0.001), whereas it had been higher in the CMD group at baseline (45% vs. 40%; p = 0.019). Similarly, during the follow-up, the CMD group had a greater incidence of AF (32.6% vs. 4.5%; p < 0.001). In the adjusted multivariable analysis, the IMR and TMAO were associated with increased odds of AF development (OR: 1.066, 95% CI: 1.018–1.117, p = 0.007), and (OR: 1.290, 95% CI: 1.002–1.660, p = 0.048), respectively. Similarly, elevated levels of IMR and TMAO were linked with decreased odds of LVEF improvement, while higher CFR values are related to a greater likelihood of LVEF improvement. Conclusions: CMD and elevated TMAO levels were highly prevalent three months after STEMI. Patients with CMD had an increased incidence of AF and a lower LVEF 12 months after STEMI. Full article

Background: Police first responder systems also including automated external defibrillation (AED) has in the past shown considerable impact on favourable outcomes after out-of-hospital cardiac arrest (OHCA). While short hands-off times in chest compressions are known to be beneficial, various AED models use different algorithms, inducing longer or shorter durations of crucial timeframes along basic life support (BLS). Yet, data on details of these differences, and also of their potential impact on clinical outcomes are scarce. Methods: For this retrospective observational study, patients with OHCA of presumed cardiac origin and initially shockable rhythm treated by police first responders in Vienna, Austria, between 01/2013 and 12/2021 were included. Data from the Viennese Cardiac Arrest Registry and AED files were extracted, and exact timeframes were analyzed. Results: There were no significant differences in the 350 eligible cases in demographics, return of spontaneous circulation, 30-day survival, or favourable neurological outcome between the used AED types. However, the Philips HS1 and -FrX AEDs showed immediate rhythm analysis after electrode placement (0 [0–1] s) and almost no shock loading time (0 [0–1] s), as opposed to the LP CR Plus (3 [0–4] and 6 [6–6] s, respectively) and LP 1000 (3 [2–10] and 6 [5–7] s, respectively). On the other hand, the HS1 and -FrX had longer analysis times of 12 [12–16] and 12 [11–18] s than the LP CR Plus (5 [5–6] s) and LP 1000 (6 [5–8] s). The duration from when the AED was turned on until the first defibrillation were 45 [28–61] s (Philips FrX), 59 [28–81] s (LP 1000), 59 [50–97] s (HS1), and 69 [55–85] s (LP CR Plus). Conclusion: In a retrospective analysis of OHCA-cases treated by police first responders, we could not find significant differences in clinical patient outcomes concerning the respective used AED model. However, various differences in time durations (e.g., electrode placement to rhythm analysis, analysis duration, or AED turned on until first defibrillation) along the BLS algorithm were seen. This opens up the question of AED-adaptations and tailored training methods for professional first responders. Full article

Atherosclerotic cardiovascular disease (ASCVD) is a silent epidemic, which is progressing relentlessly across the globe. Developing countries such as India have a high prevalence of dyslipidemia and consequently a huge burden of coronary artery disease (CAD) and ASCVD. Low-density lipoprotein is regarded as the primary culprit in the genesis of ASCVD, and statins are the first line therapy for LDL-C lowering. Statin therapy has unequivocally demonstrated the benefit of lowering LDL-C in patients across the spectrum of CAD and ASCVD. Muscle symptoms and worsening of glycemic homeostasis could be challenges with statin therapy, especially with the use of high doses. A large fraction of patients are also unable to achieve their LDL goals with statins alone in clinical practice. Moreover, LDL-C goals have become aggressive over years, necessitating a combination of lipid lowering therapies. PCSK-9 inhibitors and Inclisiran have emerged as robust and safe lipid-lowering agents, but parenteral administration and high cost precludes their widespread use. Bempedoic acid is a novel lipid-lowering agent working upstream of statins by inhibiting the enzyme ATP citrate lyase (ACL). The drug produces an average LDL lowering of 22–28% in statin-naïve patients and 17–18% when given to preexisting statin users. Because skeletal muscles lack the ACL enzyme, there is minimal risk of muscle-related symptoms. In combination with ezetimibe, the drug synergistically reduced LDL-C by 39%. Moreover, the drug has no adverse effect on glycemic parameters and lowers hsCRP (inflammation) like statin. The series of four randomized CLEAR trials, involving >4000 patients, have shown consistent LDL lowering across the spectrum of ASCVD patients with or without background therapy. The large and only cardiovascular outcome trial of the drug (CLEAR Outcomes) has recently demonstrated a 13% reduction of MACE at 40 months. Rise in levels of uric acid (four times) and acute gout (three times) are more common compared to placebo with the drug, owing to competitive renal transportation by OAT 2. In a nutshell, Bempedoic acid represents a value addition to the inventory of dyslipidemia management. Full article