Cardiovascular Medicine
The Impact of Novel Lipid-Lowering Agents on Cardiovascular Risk Reduction: A Systematic Review and Meta-Analysis
Reducing the risk of atherosclerotic cardiovascular disease is the aim of lipid-lowering therapy (ASCVD). It is commonly acknowledged that low-density lipoprotein (LDL) is a major cause of ASCVD. Several online databases and search engines such as PubMed and the Cochrane Library were used to conduct a thorough search.
This study included RCTs assessing the effect of PCSK9 inhibitors on cardiovascular events. The RevMan 5.4 software was used to conduct the meta-analysis. This analysis included nine RCTs in total.
Meta-analysis of the included studies showed that the levels of total cholesterol LDL and triglycerides were reduced after the use of PCSK9 inhibitors and HDL levels were increased which is good cholesterol. Most adverse cardiac events (MACE) were reduced after the use of PCSK9 inhibitors.
In conclusion ezetimibe a PCSK9 inhibitor added to statin therapy further reduces MACE risk without affecting all-cause mortality even though statins already significantly reduce major adverse cardiovascular events (MACE) and mortality.
Assessment of Left Ventricular Shape Index and Eccentricity Index as Promising Parameters for Detection of Left Ventricular Remodeling in Cardiovascular Events
Left ventricular remodeling (LVR) refers to the changes in the size shape and function of the left ventricle influenced by mechanical neurohormonal and genetic factors. These changes are directly linked to an increased risk of major adverse cardiac events (MACEs). Various parameters are used to assess cardiac geometry across different imaging modalities with echocardiography being the most commonly employed technique for measuring left ventricular (LV) geometry. However many echocardiographic evaluations of geometric changes primarily rely on two-dimensional (2D) methods which overlook the true three-dimensional (3D) characteristics of the LV. While cardiac magnetic resonance (CMR) imaging is considered the gold standard for assessing LV volume it has limitations including accessibility issues challenges in patients with cardiac devices and longer examination times compared to standard echocardiography. In nuclear medicine LV geometry can be analyzed using the shape index (SI) and eccentricity index (EI) which measure the sphericity and elongation of the left ventricle. Myocardial perfusion imaging (MPI) using SPECT or PET is inherently a 3D technique making it particularly effective for accurately and consistently assessing LV size and shape parameters. In this context LV metrics such as EI and SI can significantly enhance the range of quantitative assessments available through nuclear cardiology techniques with particular value in identifying early LV remodeling in specific patient groups. This article explores the diagnostic significance of left ventricular geometric indices through various diagnostic methods highlighting the important role of nuclear cardiology.
The Role of Red Blood Cells in Cholesterol Accumulation and Atherosclerotic Plaque Instability: A Perspective on Atherosclerosis
Atherosclerosis stands as the primary cause of CVD characterized by the accumulation of cholesterol deposits within macrophages in medium and large arteries. This deposition promotes the proliferation of specific cell types within the arterial wall gradually narrowing the vessel lumen and impeding blood flow. Intra-plaque hemorrhages are recognized as critical events in atherosclerotic plaques leading to the deposition of red blood cells (RBCs) and the release of hemoglobin (Hb). Approximately 40% of high-risk plaques exhibit intra-plaque hemorrhage. Recent studies have demonstrated that intra-plaque hemorrhage is closely linked to plaque progression and increased vulnerability establishing it as a critical factor in the development of acute clinical symptoms associated with atherosclerosis. The presence of RBC membranes within atherosclerotic plaques contributes significantly to lipid accumulation indicating a pivotal role in plaque instability. Upon RBC degradation cholesterol from both the membrane and its interior can profoundly impact atherosclerotic plaque development. Considering that red blood cells (RBCs) can contribute to the excretion of cholesterol through the hepatobiliary system alongside HDL and given that elevated cholesterol levels are a risk factor for the development and progression of atherosclerotic plaques RBCs may play a protective role in cardiovascular health. However when bleeding occurs within a plaque RBCs that are trapped in the plaque environment an environment rich in oxidant compounds can rupture. The cholesterol released from these ruptured RBCs can significantly promote inflammatory reactions. This study aims to explore the inconsistent role of RBCs and their cholesterol content in the progression of atherosclerotic plaques.
Safety and Efficacy of Zero Fluoroscopy Patent Ductus Arteriosus Closure in Comparison to the Standardized Fluoroscopy-Guided Procedure: A Systematic Review and Meta-Analysis
Patent Ductus Arteriosus (PDA) is a common condition in premature infants requiring intervention to avoid problems. Despite improvements in lowering radiation exposure and employing better contrast agents fluoroscopy is still the most widely employed technique which exposes interventional echocardiographers to radiation risks. Techniques such as Transthoracic Echocardiography (TTE)-guided procedures or Transesophageal Echocardiography (TEE)-guided procedures provide radiation-free options. This systematic review and meta-analysis aimed to evaluate the safety and effectiveness of fluoroscopy-guided versus non-fluoroscopy-guided PDA closure techniques with respect to the reduction in procedural risks and improved clinical decision-making when treating hemodynamically severe PDAs in premature newborns. As there is no specific age or cutoff for this procedure it is crucial to perform it as early as possible to prevent complications especially if symptoms are already present.
This systematic review has been registered in PROSPERO with registration number CRD42024516321. Three electronic databases (PubMed Scopus and Google Scholar) have been reviewed up to February 2024 to search the literature. The main outcome has been the procedural success rate. The additional outcomes have included procedural-related complications rate. We have performed a proportional meta-analysis using the random-effects model and the DerSimonian-Laird method. The risk of bias in all included studies has been evaluated using the STROBE guideline.
A total of 85 (78 fluoroscopy and 7 zero-fluoroscopy) studies have been included in this study. Percutaneous PDA closure success rate has been significantly higher in zero-fluoroscopy group compared to fluoroscopy guidance [99.4% (95%CI: 98.1-100%) and 94.6% (95%CI: 92.3-97% test for subgroup differences p < 0.01) respectively]. The complication rate has been similar in both groups [4% (95%CI: 0-10%) in zero-fluoroscopy and 8.9% (95%CI: 6.5-11.3%) in fluoroscopy group test for subgroup differences; p = 0.14]. Device embolization has been the most common complication reported in the fluoroscopy group [1.7% patients (95%CI: 1.1-2.3%)]. Meanwhile the residual leak has been the only complication reported in the zero-fluoroscopy group [15.6% patients (95%CI: 0-37.5%)].
Patent Ductus Arteriosus (PDA) is common in preemies and requires intervention. While fluoroscopy is widely used with lower radiation and better contrast agents it still carries radiation risks. Thus this review has evaluated the safety and effectiveness of fluoroscopy versus zero-fluoroscopy-guided PDA closures aiming to reduce procedural risks and enhance clinical decisions for treating PDA.
Zero fluoroscopy techniques for percutaneous PDA closure have been found to yield comparable success rates and procedural outcomes to fluoroscopy-guided procedures. Considering its reduced side effects zero-fluoroscopy is safe and can be the preferred method to guide closures. However future randomized controlled trials are necessary to better understand the exact role of interventional echocardiography in PDA closures.
The Incidence of Heart Failure in Children with Congenital Heart Disease: A Prospective Cohort Study
Pediatric heart failure (HF) poses diagnostic challenges especially in emergency settings where misdiagnoses are common.
This study aimed to investigate the causes of HF in children with congenital heart disease (CHD) and provide insights into age-related disparities and clinical classifications.
A prospective observational cohort study was conducted on 402 pediatric patients with CHD during the years 2019-2020. Ultimately 45 pediatric patients diagnosed with HF by two pediatric cardiologists based on clinical symptoms and radiographic changes were included in the study. Information from the patients' files including epidemiological findings clinical examinations paraclinical findings and interventions performed was recorded. Etiological factors and clinical classifications were analyzed using statistical tests.
Among 402 pediatric patients with CHD 45 (11.19%) were diagnosed with HF with a median age of 7.5 months. The predominant etiological factors included ventricular septal defect (VSD) atrial septal defect (ASD) and cardiomyopathy. Analysis of etiological factors revealed that single structural defects accounted for 71.11% of HF cases while concurrent defects contributed to a significant portion of the remaining cases. Clinical classifications revealed age-related differences emphasizing the heterogeneity of pediatric HF presentations.
Given that all patients with HF in our study had CHD more investigations into the causes and mechanisms of this issue are necessary which will be possible with genetic studies. A significant difference was observed between Class II and Class IV with Class II patients being older and heavier and having a lower heart rate compared to those in Class IV. This aligns with the classifications where Class II indicates mild symptoms during ordinary activity while Class IV signifies severe symptoms at rest.
Umbilical Cord Matrix (Wharton Jelly) Mesenchymal Stem Cells in Next-generation Myocardial Repair and Regeneration: Mechanisms and Pre-clinical Evidence
Chronic ischemic heart failure (CIHF) caused by myocardial injury and cell loss is a growing public health concern. Despite substantial investments in pharmaco- and device therapies for acute myocardial infarction and CIHF over the past decades long-term prognosis has shown little improvement. There is a clear need to develop novel therapeutic strategies capable of attenuating progression from acute to chronic myocardial damage reducing adverse myocardial remodeling and enhancing myocardial contractility. Cell-based approaches are an important direction in basic and clinical research. Nevertheless candidate cell types tested to-date in experimental and human studies show several fundamental limitations including insufficient quantities and potency poor myocardial uptake immunogenicity and/or risk of tumorigenicity. Human umbilical cord matrix is a rich source of mesenchymal stem cells (Wharton’s jelly mesenchymal stem cells WJMSCs). WJMSCs are naturally low-immunogenic demonstrate high plasticity and proliferation capacity and exhibit an absence of tumorigenic potential. Moreover by producing specific anti-inflammatory cytokines and chemokines they reduce the inflammatory response (hence their use in graft-versus-host disease) and have pro-angiogenic anti-apoptotic and anti-fibrotic properties making them a natural player in myocardial repair and regeneration. Furthermore WJMSCs can be expanded ex vivo with high genomic stability and full clonogenic potential and can be standardized as an “off-the-shelf” next-generation advanced therapy medicinal product (ATMP). This review aggregates essential contemporary information on the properties and fundamental mechanisms of WJMSCs addressing the process of infarct healing and chronic myocardial injury. It discusses outcomes from pre-clinical studies demonstrating improvements in myocardial function and reductions in fibrosis in animal models paving the way for human ATMP trials.
Leptin Resistance and Cardiometabolic Disorders: Bridging Molecular Pathways, Genetic Variants, and Therapeutic Innovation
Leptin a hormone produced by fat cells is crucial for regulating energy equilibrium managing body mass and influencing metabolic and cardiovascular well-being. Leptin decreases appetite boosts energy usage and has a significant impact on glucose metabolism by primarily activating the JAK2/STAT3 signaling pathway in the hypothalamus. Obesity leads to the development of leptin resistance which is marked by high levels of leptin in the bloodstream and a decreased responsiveness to its signals. This leads to increased food consumption weight gain and metabolic issues such as type 2 diabetes (T2DM) and cardiovascular disease (CVD). This study explores the many roles of leptin in metabolic regulation with a specific emphasis on its interaction with insulin and its impact on peripheral organs like the pancreas liver and muscles. Leptin resistance worsens chronic inflammation oxidative stress endothelial dysfunction and insulin resistance all of which are strongly linked to the development of cardiovascular disease (CVD). Moreover there is a correlation between genetic variations in the leptin receptor (LEPR) gene and a higher susceptibility to stroke and other cardiovascular issues. Therapeutic interventions such as leptin replacement therapy have demonstrated potential in the treatment of congenital leptin insufficiency and lipodystrophy while also enhancing glycaemic control lipid profiles and neuroendocrine function. Recent studies have indicated that manipulating leptin levels or enhancing its responsiveness by specific treatments such as chemical chaperones and inhibitors of negative regulators like SOCS3 and PTP1B might potentially restore the efficacy of leptin.
A New Mechanism of Supraventricular Tachycardia: Gene Mutation
Supraventricular tachycardia (SVT) is very common in daily clinical practice especially in the emergency department with rapid onset and urgent management. The review highlights the recent genetic predispositions and mechanisms in SVT.
Through analysis of epidemiology familial clustering and gene mutations of the relevant literature the review elucidates the genetic properties and potential pathophysiology of SVT.
There are many pathophysiological mechanisms related to atrioventricular node reentrant tachycardia (AVNRT) and atrioventricular reentrant tachycardia (AVRT). Currently there is relatively little research on inappropriate sinus tachycardia (IST) atrial tachycardia (AT) and congenital junctional ectopic tachycardia (CJET). It seems that every type of SVT has gene mutations in ion channels with three types of SVT having gene mutations in signaling pathways and others including gene mutations in beta-adrenergic-receptor autoantibodies autonomic nervous system and AV node structure.
SVT has certain genetic characteristics and is often associated with other heart diseases. From the analysis of mutated genes in SVT it appears to be a type of cardiac ion channel disease. Unlike common ion channel diseases it is more insidious and more susceptible to external factors. The confirmation of the genetic basis of SVT provides direction for future hazard stratification assessment and gene targeted therapy drug research.
Prevalence and Adverse Outcomes of Iron Deficiency in Heart Failure
Outcomes of iron deficiency (ID) in heart failure (HF) with preserved ejection fraction (HFpEF) or in samples with mixed heart failure subtypes are variably described. Hence we investigated the prevalence and adverse outcomes of ID in a sample of mixed heart failure subtypes.
Adult patients admitted with HF over a six-month period were retrospectively studied. ID was defined as serum ferritin<100 mcg/L or serum ferritin 100-300 mcg/L with serum transferrin saturation<20%. For each case of ID sex- and age-matched (within five years) controls were selected. The primary outcome was the composite of all-cause mortality or readmissions up to 12 months post-index admission.
Of the 245 patients admitted with HF [HFpEF: 83 (70.3%) HFrEF: 35 (29.6%)] 233 met the inclusion criteria. Iron studies were available for 131 patients and 59 (45%) had ID. ID had a significant univariate association with the primary outcome (OR: 3.80 95% CI: 1.42–10.18 P=0.008) and it remained significant after controlling for age anaemia comorbidities and frailty (OR: 6.04 95% CI: 1.18–30.85 P=0.031). ID also had a significant independent association with readmissions (OR: 4.61 95% CI: 1.15–18.43 P=0.03) but not with mortality (OR: 1.17 95% CI: 0.67-4.35 P=0.257). In post-hoc analysis ID exhibited a significant association with primary outcome in patients with HFrEF (OR: 14.12 95% CI: 1.7-117.33 P=0.014) but not in patients with HFpEF (OR: 1.8 95% CI: 0.71-4.58 P=0.214).
ID is common in patients hospitalised for heart failure and has been found to have a significant association with the composite primary outcome largely due to its effect on readmissions. ID may have a differential effect on adverse outcomes with respect to heart failure subtypes.
Cardiotoxicity of Microplastics: An Emerging Cardiovascular Risk Factor
The widespread use of plastics and improper disposal have resulted in the ubiquity of microplastics in the environment from uninhabited polar regions to terrestrial ecosystems. This ubiquity poses significant health concerns for our environment and health. Various in vitro in vivo and ex vivo studies have indicated microplastic toxicity in humans' respiratory digestive neurological reproductive and developmental health. Recent studies have pointed out that these microplastics also have cardiovascular toxicity. Cardiovascular diseases (CVDs) are the number one killer in the world with over 20 million annual deaths worldwide. Hence microplastics as a potential risk factor for CVDs can result in a significant increase in mortality and morbidity because almost everyone is currently exposed to microplastics. This perspective article explores the toxic effects of microplastics on cardiovascular human health. It focuses on various studies that have found microplastics from human arteries/cardiac tissues and their potential role in atherosclerosis and subsequent increases in myocardial infarction stroke and mortality. Studies reported the presence of various microplastics such as polyethylene polyvinyl chloride polyamide and polystyrene in cardiac tissues and arteries (coronary aorta cerebral and carotid). Studies have suggested a potential negative correlation between microplastics and cardiovascular health with the presence or increased concentration of microplastics linked to greater severity of health issues. Still a causal relationship is yet to be established. Future studies such as cohorts should focus on deciphering and establishing whether microplastics are a potential cardiovascular risk factor.
Slowing Thoracic Aortic Aneurysm Growth with Statins: A Meta-Analysis
Thoracic aortic aneurysms (TAAs) are worrisome for their propensity to dissect. Previous studies have demonstrated the potential benefits of statin use particularly with slowing aortic aneurysm growth. The aim of this meta-analysis was to consolidate existing research to ascertain if statins effectively reduce TAA growth.
Multiple databases were searched to identify studies assessing TAA growth in patients on statins (cases) and those not on statins (controls). The primary outcome was TAA (ascending/aortic arch) growth rate per year. Standard mean difference (SMD) and 95% confidence intervals (95% CI) were estimated with a random-effects model using the inverse-variance technique. We assigned I2>50% as an indicator of statistical heterogeneity. P-value <0.05 was considered significant. Data analysis was performed using SPSS v.25.0.
Four studies comprising 757 cases (male 64% mean age 65±14 years) and 1696 controls (male 62% mean age 61±18 years) were included. The baseline diameters of TAA for cases and controls were 40.35±8.75 mm and 42.39±12.60 mm respectively. Pooled results suggested statins to be associated with slower growth of TAAs with pooled SMD -0.70 mm/year [95% CI (-1.23 – -0.16); p=0.01]. Heterogeneity statistics among 4 studies was 95%.
This pooled meta-analysis showed statins as associated with slower growth of TAAs. However given the heterogeneity of the included studies in this meta-analysis results should be interpreted with caution.