Cardiac Arrhythmias in Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension: Mechanistic Insights, Pathophysiology, and Outcomes.

Arrhythmias are increasingly recognized as severe complications of precapillary pulmonary hypertension, encompassing pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Despite their significant contribution to symptoms, morbidity, in-hospital mortality, and potentially sudden death in PAH/CTEPH, there remains a lack of comprehensive data on epidemiology, pathophysiology, and outcomes to inform the management of these patients. This review provides an overview of the latest evidence on this subject, spanning from the molecular mechanisms underlying arrhythmias in the hypertrophied or failing right heart to the clinical aspects of epidemiology, diagnosis, and treatment.

Pectoral Nerve Block II for Cardiac Implantable Electronic Devices.

AIM: This study aimed to assess the feasibility and effectiveness of the pectoral nerves (PECS) II block in facilitating cardiac implantable electronic device (CIED) insertion in a sample of 120 patients, with a focus on the percentage of cases completed without additional intraoperative local anesthesia. METHODS: PECS II blocks were performed on the left side using ultrasound guidance in all 120 patients. Feasibility was assessed by the proportion of cases completed without the need for extra intraoperative local anesthetic. Secondary outcomes included the amount of additional local anesthetic used, intraoperative opioid requirements, postoperative pain scores, time to first postoperative analgesia, analgesic consumption, patient satisfaction, and block-related complications. RESULTS: Of the 120 patients, 78 (65%) required additional intraoperative local anesthetic, with a median volume of 8.2 mL (range 3-13 mL). Fifteen patients (12.5%) needed intraoperative opioid supplementation. Nine patients (7.5%) required postoperative tramadol for pain relief. In total, 98 patients (81.7%) reported high satisfaction levels with the procedure. CONCLUSIONS: The PECS II block, when combined with supplementary local anesthetic, provided effective postoperative analgesia for at least 24 h in 120 patients undergoing CIED insertion. While it did not completely replace surgical anesthesia in most cases, the PECS II block significantly contributed to a smoother intraoperative experience for patients.

Outcomes of dual-chamber implantable cardioverter defibrillator for left bundle branch area pacing: A systematic review of literature.

OBJECTIVE: This systematic review of literature aimed to evaluate the safety and efficacy of dual-chamber ICDs for LBBAP in patients with left bundle branch block (LBBB). METHODS: Digital databases were searched systematically to identify studies reporting the left bundle branch area pacing (LBBAP) with implantable cardioverter defibrillator (ICD) placement in patients with LBBB. Detailed study and patient-level baseline characteristics including the type of study, sample size, follow-up, number of cases, age, gender, and baseline characteristics were abstracted. RESULTS: In a total of three studies, 34 patients were included in this review. There was a significant improvement reported in QRS duration in all studies. The mean QRS duration at baseline was 170 ± 17.4 ms, whereas the follow-up QRS duration at follow-up was 121 ± 17.3 ms. Two studies reported a significant improvement of 50% in LVEF from baseline. No lead-related complications or arrhythmic events were recorded in any study. The findings of the systematic review suggest that dual-chamber ICD for LBBAP is a promising intervention for patients with heart conditions. CONCLUSION: The procedure offers significant improvements in QRS duration and LVEF, and there were no lead-related complications or arrhythmic events recorded in any of the studies.

Efficacy and safety of cardiac resynchronization therapy in chemotherapy-induced cardiomyopathy: A systematic review.

OBJECTIVE: The aim of the study was to assess the efficacy of cardiac resynchronization therapy (CRT) in patients with chemotherapy-induced cardiomyopathy (CIC). METHODS: With the increasing incidence of CIC, the association of CRT with improvement in clinical outcomes, echocardiographic parameters, and New York Heart Classification (NYHA) class was assessed through this qualitative systematic review. RESULTS: The five studies included a total of 169 patients who underwent CRT after CIC, and of these, 61 (36.1%) patients were males. All studies showed an improvement in left ventricular ejection fraction (LVEF), among other echocardiographic parameters of LV volume. However, these findings are limited by short follow-up periods, small sample sizes, and the absence of a control group. CONCLUSION: CRT was associated with improvement in all patient parameters with CIC.

Predicting stroke and mortality in mitral stenosis with atrial flutter: A machine learning approach.

BACKGROUND: Our study hypothesized that an intelligent gradient boosting machine (GBM) model can predict cerebrovascular events and all-cause mortality in mitral stenosis (MS) with atrial flutter (AFL) by recognizing comorbidities, electrocardiographic and echocardiographic parameters. METHODS: The machine learning model was used as a statistical analyzer in recognizing the key risk factors and high-risk features with either outcome of cerebrovascular events or mortality. RESULTS: A total of 2184 patients with their chart data and imaging studies were included and the GBM analysis demonstrated mitral valve area (MVA), right ventricular systolic pressure, pulmonary artery pressure (PAP), left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) class, and surgery as the most significant predictors of transient ischemic attack (TIA/stroke). MVA, PAP, LVEF, creatinine, hemoglobin, and diastolic blood pressure were predictors for all-cause mortality. CONCLUSION: The GBM model assimilates clinical data from all diagnostic modalities and significantly improves risk prediction performance and identification of key variables for the outcome of MS with AFL.

Echocardiography- versus intracardiac electrocardiogram-based optimization of cardiac resynchronization therapy: A systematic review.

OBJECTIVE: This systematic review aimed to evaluate the performance of echocardiography-based programming in comparison with the intracardiac electrocardiogram (IEGM)-based method for the optimization of cardiac resynchronization therapy (CRT). METHODS: A literature review was conducted using digital databases to systematically identify the studies reporting CRT optimization through echocardiography compared with IEGM. Detailed patient-level study characteristics including the type of study, sample size, therapy, the New York Heart Classification (NYHA) status, lead placement, and other parameters were abstracted. Finally, postprogramming outcomes were extracted for each article. RESULTS: In a total of 11 studies, 919 patients were recruited for the final analysis. Overall, 692 (75.29%) were males. The mean duration of the QRS complex in our study population ranged from 145.2 ± 21.8 ms to 183 ± 19.9 ms. There was an equal improvement in the NYHA class between the two methods while the left ventricular ejection fraction (LVEF) demonstrated an improvement by IEGM. Many studies supported IEGM to increase the 6-minute walk test and left ventricular outflow tract velocity time interval (LVOT VTI) when compared to echocardiography. The mean time for echocardiography-based optimization was 60.15 min while that of IEGM-based optimization was 6.65 min. CONCLUSION: IEGM is an alternative method for CRT optimization in improving the NYHA class, LVEF, and LVOT VTI, and is less time-consuming when compared to the echocardiography-based methods.

Association of gut microbiome dysbiosis with the progression of atrial fibrillation: A systematic review.

OBJECTIVE: Many clinical and preclinical studies have implicated an association between atrial fibrillation (AF) and its progression to imbalances in the gut microbiome composition. The gut microbiome is a diverse and complex ecosystem containing billions of microorganisms that produce biologically active metabolites influencing the host disease development. METHODS: For this review, a literature search was conducted using digital databases to systematically identify the studies reporting the association of gut microbiota with AF progression. RESULTS: In a total of 14 studies, 2479 patients were recruited for the final analysis. More than half (n = 8) of the studies reported alterations in alpha diversity in atrial fibrillation. As for the beta diversity, 10 studies showed significant alterations. Almost all studies that assessed gut microbiota alterations reported major taxa associated with atrial fibrillation. Most studies focused on short-chain fatty acids (SCFAs), whereas three studies evaluated TMAO levels in the blood, which is the breakdown product of dietary l-carnitine, choline, and lecithin. Moreover, an independent cohort study assessed the relationship between phenylacetylglutamine (PAGIn) and AF. CONCLUSION: Intestinal dysbiosis is a modifiable risk factor that might provide newer treatment strategies for AF prevention. Well-designed research and prospective randomized interventional studies are required to target the gut dysbiotic mechanisms and determine the gut dysbiotic-AF relationship.

Outcomes of primary leadless pacemaker implantation: A systematic review.

BACKGROUND: During the last decade, leadless pacemakers (LPMs) have turned into a prevalent alternative to traditional transvenous (TV) pacemakers; however, there is no consolidated data on LPM implantation in emergencies. METHODS: Digital databases were searched for this review and four relevant studies, including 1276 patients were included in this review with procedure duration, fluoroscopic time, major complications, and mortality as primary outcomes and pacing threshold, impedance, sensing of LPM, and hospital stay as secondary outcomes. RESULTS: Gonzales et al. and Marschall et al. showed the duration of the procedure to be 180 ± 45 versus 324.6 ± 92 and 39.9 ± 8.7 versus 54.9 ± 9.8, respectively. Zhang et al. demonstrated the duration of the procedure and fluoroscopy time to be 36 ± 13.4 and 11.1 ± 3.1, respectively. Similarly, Schiavone et al. exhibited intermediate times of implantation at 60 (45-80) versus 50 (40-65) and fluoroscopic times at 6.5 (5-9.7) versus 5.1 (3.1-9). Hospital stay was more with a temp-perm pacemaker as compared to LPM and pacing parameters were not significantly different in all the studies. CONCLUSION: For underlying arrhythmias, whenever appropriate, our review shows that LPMs may be a better option than temporary pacemakers, even as an urgent treatment.

Tricuspid regurgitation in His bundle pacing: A systematic review.

OBJECTIVE: This systematic review aimed to explore an association of new TR and its quantification in patients undergoing His bundle pacing (HBP). METHODS: A literature review was conducted using Mesh terms (His bundle pacing, tricuspid regurgitation, tricuspid valve incompetence, etc.) in PubMed, EMBASE, Web of science CINAHL, and the Cochrane Library till October 2021. Relevant studies evaluating tricuspid regurgitation in HBP were included and information regarding TR and its related factors (ejection fraction (EF) and New York Heart Association (NYHA) class) were retrieved from the eligible studies. RESULTS: Out of 196 articles, 10 studies met the inclusion criteria, which consisted of 546 patients with HBP. The mean age of the patients ranged between 61.2 ± 12.3 and 75.1 ± 7.9 years with 54.1% males. The overall implant success rate was 79.2%. Only one study reported a 5% incidence of TR, while 9 studies reported no new TR after HBP. Four studies reported overall decrease in TR by 1 grade and 3 studies demonstrated increased TR from baseline. Two studies showed no change from baseline TR. CONCLUSION: HBP causes improvement in TR grade after HBP for cardiac resynchronization therapy (CRT) as well as atrioventricular block (AVB). Further studies in the form of randomized controlled trials are required to further evaluate the effect of HBP on tricuspid valve functioning.

Cardiovascular Interventions in Patients With Active and Advanced Malignancy: An Updated Review.

In the context of active, advanced malignancies, the recommendation for invasive cardiac interventions is grounded primarily in evidence from trials focused on specific cardiovascular conditions. However, the inclusion of individuals with advanced malignancies in these trials has historically been limited, and the intricate interplay between cancer and cardiovascular disease poses unique challenges for treatment decisions. In this comprehensive review, we delve into the complex landscape of invasive cardiac interventions and their applicability in patients with active, advanced cancer. Our analysis encompasses a range of cardiovascular scenarios, including ST-segment elevation myocardial infarction, non-ST-segment elevation acute coronary syndromes, multivessel coronary disease, severe symptomatic aortic stenosis, and cardiomyopathy. We critically examine the available data and evidence, shedding light on the benefits and potential risks associated with invasive cardiac procedures in the presence of advanced malignancies. Acknowledging the competing risk of mortality posed by advanced cancers, we delve into the contemporary survival expectations for patients across various types of active, advanced malignancies. By synthesizing current literature and exploring cardiovascular interventions within these populations, we aim to establish a well-informed framework. Our ultimate goal is to provide clinicians with a rational guide for making nuanced clinical recommendations regarding the utilization of invasive cardiac interventions in the challenging context of active, advanced cancer.

Physicians' Perspective on Percutaneous Left Atrial Appendage Closure in Patients with Atrial Fibrillation and Chronic Kidney Disease in Pakistan.

This study, conducted in Pakistan, examines the perspectives of 1200 physicians across diverse specialties regarding Left Atrial Appendage Occlusion (LAAO) procedures for atrial fibrillation (AF) patients with chronic kidney disease (CKD). Using a random sampling approach, physicians participated in a survey that assessed their familiarity with LAAO, views on its effectiveness and safety, experience levels, and encountered challenges. The results unveil a spectrum of knowledge levels among physicians, reinforcing the need for tailored medical education and training programs. The majority of respondents were between 30 and 49 years old (59.8 %). A notable proportion, 33.3 %, had limited or no knowledge of LAAO, with 16.7 % having never heard of the procedure, and 16.7 % having limited knowledge but no experience. About 36.2 % of physicians believed LAAO was moderately to extremely effective in reducing stroke risk, with 23.3 % considering it very effective and 25.4 % believing it to be extremely effective. The most commonly cited clinical indications were a history of recurrent strokes despite anticoagulation (34.6 %) and a high CHA2DS2-VASc score (27.3 %). Renal considerations played a significant role, with 33.1 % considering LAAO for CKD stage 4 or 5 patients with elevated stroke risk. Patient preferences, such as a desire to avoid long-term anticoagulant use, were important for 28.7 % of physicians. Identified challenges encompass limited equipment access, training gaps, patient reluctance, and administrative complexities. Furthermore, the study underscores the pivotal role of shared decision-making in healthcare delivery. These findings lay essential groundwork for improving LAAO utilization and patient-centered care in Pakistan's healthcare system.

Association of transportation noise with cardiovascular diseases.

This comprehensive article delves into the intricate and multifaceted issue of noise pollution, shedding light on its diverse sources, profound health implications, and the economic burden it imposes on societies. Noise pollution is an increasingly prevalent environmental challenge, impacting millions of people worldwide, often without their full awareness of its adverse effects. Drawing from a wealth of scientific research, the article underscores the well-established links between noise pollution and a spectrum of health issues, including cardiovascular diseases, sleep disturbances, and psychological stress. While exploring the sources and consequences of noise pollution, the article highlights the urgent need for a holistic and collaborative approach to mitigate its impact. This entails a combination of regulatory measures, technological innovations, urban planning strategies, and public education campaigns. It is increasingly evident that the detrimental effects of noise pollution extend beyond physical health, encompassing mental and social well-being. The article also addresses the synergistic relationship between noise pollution and other environmental stressors, emphasizing the importance of considering noise in conjunction with factors like air pollution and access to green spaces. It examines the potential of green spaces to mitigate the effects of noise pollution and enhance overall health.

Bridging With Low-Molecular-Weight Heparin Versus Antiplatelet Therapy in Patients Undergoing Noncardiac Surgery After Percutaneous Coronary Intervention: A Comprehensive Review.

BACKGROUND: This review article discussed the use of bridging therapy with low-molecular-weight heparin (LMWH) in patients who undergo noncardiac surgery (NCS) after percutaneous coronary intervention (PCI). HYPOTHESES: Patients who undergo PCI are at an increased risk of thrombotic events due to their underlying cardiovascular disease. However, many of these patients may require NCS at some point in their lives, which poses a significant challenge for clinicians as they balance the risk of thrombotic events against the risk of bleeding associated with antithrombotic therapy. RESULTS: This review evaluates the current evidence on the use of bridging therapy with LMWH in patients undergoing NCS after PCI, focusing on outcomes related to the efficacy and safety of antithrombotic therapy. The article also discusses the limitations of the current evidence and highlights areas where further research is needed to optimize the management of antithrombotic therapy in this patient population. CONCLUSION: The goal of this review was to provide clinicians with a comprehensive summary of the available evidence to guide clinical decision-making and improve patient outcomes.

Cardiovascular risk assessment in inflammatory bowel disease with coronary calcium score.

The interplay between inflammatory bowel disease (IBD) and atherosclerotic cardiovascular disease (ASCVD) underscores the intricate connections between chronic inflammation and cardiovascular health. This review explores the multifaceted relationship between these conditions, highlighting the emerging significance of the coronary calcium score as a pivotal tool in risk assessment and management. Chronic inflammation, a hallmark of IBD, has far-reaching systemic effects that extend to the cardiovascular system. Shared risk factors and mechanisms, such as endothelial dysfunction, lipid dysfunction, and microbiome dysregulation, contribute to the elevated ASCVD risk observed in individuals with IBD. Amidst this landscape, the coronary calcium score emerges as a means to quantify calcified plaque within coronary arteries, offering insights into atherosclerotic burden and potential risk stratification. The integration of the coronary calcium score refines cardiovascular risk assessment, enabling tailored preventive strategies for individuals with IBD. By identifying those at elevated risk, healthcare providers can guide interventions, fostering informed shared decision-making. Research gaps persist, prompting further investigation into mechanisms linking IBD and ASCVD, particularly in the context of intermediate mechanisms and early atherosclerotic changes. The potential of the coronary calcium score extends beyond risk assessment-it holds promise for targeted interventions. Randomized trials exploring the impact of IBD-modifying therapies on ASCVD risk reduction can revolutionize preventive strategies. As precision medicine gains prominence, the coronary calcium score becomes a beacon of insight, illuminating the path toward personalized cardiovascular care for individuals living with IBD. Through interdisciplinary collaboration and rigorous research, we embark on a journey to transform the paradigm of preventive medicine and enhance the well-being of this patient population.

Efficacy and Safety of Pressure-controlled Intermittent Coronary Sinus Occlusion in STEMI: A Systematic Review and Meta-analysis.

This systematic review will provide a comprehensive assessment of the evidence on PICSO in STEMI patients, and it will help to determine the role of this novel technique in the management of STEMI. The review searched for the relevant articles in the PubMed, Embase, Cochrane Library, and Web of Science databases regarding PC-ICSO. Four cohort studies were eligible to be included in the quantitative analysis. In the pooled analysis, the use of PICSO was associated with a significant reduction in infarct size (SMD = -0.44, 95% CI = -0.76,-0.13, p = 0.004). PICSO administration was associated with a reduced risk of developing microvascular resistance (RR = 0.75, 95% CI = 0.62,0.92, p = 0.0051). The post-procedural Index of Microvascular Occlusion (MVO) was lower in the PICSO treated compared to the control group and this result was homogenous and statistically significant (SMD = -0.35, 95% CI = -0.68-0.01, p = 0.03, I2 = 0%). Compared to matched controls, the use of PICSO was associated with higher Left Ventricular Ejection Fraction (LVEF) at the longest follow-up (SMD = 0.328, 95% CI = 0.03, 0.06, p = 0.03, I2 = 0%). This review suggested that PICSO can be used during PPCI in STEMI with improved outcomes of infarct size, LVEF, and microvascular perfusion.

Efficacy and Safety of Bempedoic Acid in Patients With Hyperlipidemia and Non-alcoholic Fatty Liver Disease.

Hyperlipidemia and its association with cardiovascular diseases have been significant public health concerns for many decades. Statins have long been the primary therapeutic option for lowering cholesterol levels and reducing cardiovascular mortality. However, a substantial number of patients either do not achieve optimal lipid goals with maximally tolerated statin doses or experience statin intolerance. In recent years, there have been remarkable developments in the field of hyperlipidemia management, leading to the approval of novel hypolipidemic drugs in North America and Europe. This article reviews the clinical development of bempedoic acid, a promising new drug, alone and in combination with ezetimibe, as an alternative approach to managing hyperlipidemia. The Phase I trials established the safety and tolerability of bempedoic acid, paving the way for further investigation in Phase II and Phase III trials. Multiple phase II studies evaluated the lipid-lowering efficacy of bempedoic acid as monotherapy or in combination with other hypolipidemic agents, showing significant improvements in lipid levels and inflammatory markers. The recently approved fixed drug combination of bempedoic acid and ezetimibe presents a viable option for patients who need additional LDL-C lowering alongside dietary modifications and maximally tolerated statin therapy.

Percutaneous Coronary Intervention in Patients with Coronary Artery Ectasia: A Retrospective Single-center Study.

Objective: This retrospective single-center study aimed to compare the outcomes of ad-hoc versus planned percutaneous coronary intervention (PCI) in patients with coronary ectasia. We investigated baseline characteristics, primary and secondary outcomes, and predictors of mortality in a cohort of patients who underwent PCI procedures. Methods: Data from 3,179 patients (ad-hoc PCI, n = 1,286; planned PCI, n = 1,893) with coronary ectasia were analyzed. Baseline characteristics, including age, gender, comorbidities, and lesion characteristics, were compared between the two groups. Primary outcomes included technical success and stent deployment success, while secondary outcomes encompassed major adverse cardiovascular events (MACE), all-cause mortality, recurrent angina, and target lesion revascularization. Logistic regression was utilized to identify predictors of mortality. Results: The ad-hoc PCI group exhibited a higher prevalence of comorbidities, including hypertension, diabetes mellitus, smoking history, and multi-vessel disease (all p < 0.05). While technical success and stent deployment success rates were lower in the ad-hoc PCI group (p < 0.05), patients undergoing planned PCI demonstrated significantly lower rates of MACE, all-cause mortality, recurrent angina, and target lesion revascularization (all p < 0.05). Logistic regression analysis identified older age, male gender, hypertension, diabetes mellitus, smoking history, and multi-vessel disease as independent predictors of mortality (all p < 0.05). Importantly, coronary ectasia emerged as an additional predictor of mortality (p = 0.002). Conclusion: Our study indicates that planned PCI is associated with improved procedural outcomes and lower rates of mortality and adverse events compared to ad-hoc PCI in patients with coronary ectasia.

Sex disparity of DAPT noncompliance in patients with left main stem PCI with DES.

This retrospective study aims to explore the sex disparity in dual antiplatelet therapy (DAPT) noncompliance among left main stem percutaneous coronary intervention (PCI) patients with drug-eluting stent (DES) and identify predictors associated with non-adherence. Data were collected from the medical records of 1585 patients, including 1104 males and 481 females, who underwent left main stem PCI with DES. Baseline characteristics, angiographic features, and DAPT compliance rates at 1 month and 12 months were analyzed. Univariate logistic regression was used to identify predictors of DAPT noncompliance. The overall DAPT noncompliance rate at 1 month was 8.5%, increasing to 15.5% at 12 months. Females exhibited slightly higher noncompliance rates than males at both 1 month (15.6% vs 14.5%) and 12 months (28.1% vs 19.0%), although the difference was not statistically significant. Smoking status showed a modest impact on non-adherence, with current smokers exhibiting a lower noncompliance rate (14.9% at 1 month). Prior coronary artery disease history was associated with increased noncompliance at 12 months (18.9%). Angiographic characteristics, including lesion location and Syntax score, had no consistent association with DAPT noncompliance. This study highlights sex disparity in DAPT noncompliance among patients undergoing left main stem PCI with DES. Comorbidities, socioeconomic status, smoking status, and prior coronary artery disease history were identified as predictors of non-adherence.

Cardiovascular effects of long-duration space flight.

Introduction: Early studies exploring the physiological effects of space travel have indicated the body's capacity for reversible adaptation. However, the impact of long-duration spaceflight, exceeding 6 months, presents more intricate challenges. Effects on the Cardiovascular CV System: Extended exposure to microgravity and radiation profoundly affects the CV system. Notable phenomena include fluid shifts toward the head and modified arterial pressure. These changes disrupt blood pressure regulation and elevate cardiac output. Additionally, the loss of venous compression leads to a reduction in central venous pressure. Fluid and Plasma Volume Changes: The displacement of fluid from the vascular system to the interstitium, driven by baroreceptor stimulation, results in a 10%-15% decline in plasma volume. Cardiac Muscle and Hematocrit Variations: Intriguingly, despite potential increases in cardiac workload, cardiac muscle atrophy and perplexing variations in hematocrit levels have been observed. The mechanism underlying atrophy appears to involve a shift in protein synthesis from the endoplasmic reticulum to the mitochondria via mortalin-mediated mechanisms. Arrhythmias and QT Interval Prolongation: Instances of arrhythmias have been recurrently documented, although generally nonlethal, in both Russian and American space missions. Long-duration spaceflight has been associated with the prolongation of the QT interval, particularly in extended missions. Radiation Effects: Exposure of the heart to the proton and heavy ion radiation pervasive in deep space contributes to coronary artery degeneration, augmented aortic stiffness, and carotid intima thickening through collagen-mediated processes. Moreover, it accelerates the onset of atherosclerosis and triggers proinflammatory responses. Reentry and Postflight Challenges: Upon reentry, astronauts frequently experience orthostatic intolerance and altered sympathetic responses, which bear potential hazards in scenarios requiring rapid mobilization or evacuation. Conclusion: Consequently, careful monitoring of these cardiac risks is imperative for forthcoming missions. While early studies illuminate the adaptability of the body to space travel's challenges, the intricacies of long-duration missions and their effects on the CV system necessitate continued investigation and vigilance to ensure astronaut health and mission success.

Role of PCSK9 inhibition during the inflammatory stage of SARS-COV-2: an updated review.

The potential role of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition in the management of COVID-19 and other medical conditions has emerged as an intriguing area of research. PCSK9 is primarily known for its impact on cholesterol metabolism, but recent studies have unveiled its involvement in various physiological processes, including inflammation, immune regulation, and thrombosis. In this abstract, the authors review the rationale and potential implications of PCSK9 inhibition during the inflammatory stage of SARS-CoV-2 infection. Severe cases of COVID-19 are characterized by an uncontrolled inflammatory response, often referred to as the cytokine storm, which can lead to widespread tissue damage and organ failure. Preclinical studies suggest that PCSK9 inhibition could dampen this inflammatory cascade by reducing the production of pro-inflammatory cytokines. Additionally, PCSK9 inhibition may protect against acute respiratory distress syndrome (ARDS) through its effects on lung injury and inflammation. COVID-19 has been linked to an increased risk of cardiovascular complications, especially in patients with pre-existing cardiovascular conditions or dyslipidemia. PCSK9 inhibitors are known for their ability to lower low-density lipoprotein (LDL) cholesterol levels by enhancing the recycling of LDL receptors in the liver. By reducing LDL cholesterol, PCSK9 inhibition might protect blood vessels from further damage and lower the risk of atherosclerotic plaque formation. Moreover, PCSK9 inhibitors have shown potential antithrombotic effects in preclinical studies, making them a potential avenue to mitigate the increased risk of coagulation disorders and thrombotic events observed in COVID-19. While the potential implications of PCSK9 inhibition are promising, safety considerations and possible risks need careful evaluation. Hypocholesterolemia, drug interactions, and long-term safety are some of the key concerns that should be addressed. Clinical trials are needed to establish the efficacy and safety of PCSK9 inhibitors in COVID-19 patients and to determine the optimal timing and dosing for treatment. Future research opportunities encompass investigating the immune response, evaluating long-term safety, exploring combination therapy possibilities, and advancing personalized medicine approaches. Collaborative efforts from researchers, clinicians, and policymakers are essential to fully harness the therapeutic potential of PCSK9 inhibition and translate these findings into meaningful clinical outcomes.