2024 update in heart failure

ESC Heart Failure, Journal Year: 2024, Volume and Issue: unknown

Published: May 28, 2024

Abstract In the last years, major progress has occurred in heart failure (HF) management. The 2023 ESC focused update of 2021 HF guidelines introduced new key recommendations based on results years science. First, two drugs, sodium–glucose co‐transporter‐2 (SGLT2) inhibitors and finerenone, a novel nonsteroidal, selective mineralocorticoid receptor antagonist (MRA), are recommended for prevention patients with diabetic chronic kidney disease (CKD). Second, SGLT2 now treatment across entire left ventricular ejection fraction spectrum. benefits quadruple therapy reduced (HFrEF) well established. Its rapid early up‐titration along close follow‐up frequent clinical laboratory re‐assessment after an episode acute (the so‐called ‘high‐intensity care’ strategy) was associated better outcomes STRONG‐HF trial. Patients experiencing worsening might require fifth drug, vericiguat. STEP‐HFpEF‐DM STEP‐HFpEF trials, semaglutide 2.4 mg once weekly administered 1 year decreased body weight significantly improved quality life 6 min walk distance obese preserved (HFpEF) or without history diabetes. Further data safety efficacy, including also hard endpoints, needed to support addition acetazolamide hydrochlorothiazide standard diuretic regimen hospitalized due HF. meantime, PUSH‐AHF supported use natriuresis‐guided therapy. options most recent evidence HF, specific drugs cardiomyopathies (i.e., mavacamten hypertrophic cardiomyopathy tafamidis transthyretin cardiac amyloidosis), device therapies, contractility modulation percutaneous valvulopathies, finding from TRILUMINATE Pivotal trial, reviewed this article.

Language: Английский

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COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 24, 2024

Our understanding of COVID-19 vaccinations and their impact on health mortality has evolved substantially since the first vaccine rollouts. Published reports from original randomized phase 3 trials concluded that mRNA vaccines could greatly reduce symptoms. In interim, problems with methods, execution, reporting these pivotal have emerged. Re-analysis Pfizer trial data identified statistically significant increases in serious adverse events (SAEs) group. Numerous SAEs were following Emergency Use Authorization (EUA), including death, cancer, cardiac events, various autoimmune, hematological, reproductive, neurological disorders. Furthermore, products never underwent adequate safety toxicological testing accordance previously established scientific standards. Among other major topics addressed this narrative review are published analyses harms to humans, quality control issues process-related impurities, mechanisms underlying (AEs), immunologic basis for inefficacy, concerning trends based registrational data. The risk-benefit imbalance substantiated by evidence date contraindicates further booster injections suggests that, at a minimum, should be removed childhood immunization program until proper studies conducted. Federal agency approval blanket-coverage population-wide had no support an honest assessment all relevant commensurate consideration risks versus benefits. Given extensive, well-documented unacceptably high harm-to-reward ratio, we urge governments endorse global moratorium modified questions pertaining causality, residual DNA, aberrant protein production answered.

Language: Английский

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Determinants of COVID-19 vaccine-induced myocarditis

Therapeutic Advances in Drug Safety, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 1, 2024

Background: Following the roll-out of Pfizer-BioNTech BNT162b2, Moderna mRNA-1273, and Janssen Ad26.COV2.S coronavirus disease 2019 (COVID-19) injections in United States, millions individuals have reported adverse events (AEs) using vaccine reports system (VAERS). The objective this analysis is to describe myocarditis data VAERS COVID-19 vaccines as potential determinants myocarditis. Methods: We used examine frequency reporting since beginning mass vaccination campaign compared with historical values administration from Our World Data database. examined context sex, age, dose. Statistical was done Student’s t-test determine statistically significant differences between ages among chi-square test relationships categorical variables statistical significance. Results: found number after 2021 223 times higher than average all combined for past 30 years. This represented a 2500% increase absolute first year when comparing prior 2021. Demographic revealed that occurred most youths (50%) males (69%). A total 76% cases resulted emergency care hospitalization. Of reports, 92 died (3%). Myocarditis more likely dose 2 ( p < 0.00001) less years age were older acquire 0.00001). Conclusion: strongly associated serious safety signal myocarditis, particularly children young adults resulting hospitalization death. Further investigation into underlying mechanisms vaccine-induced imperative create effective mitigation strategies ensure programs across populations.

Language: Английский

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COVID-19 Modified mRNA “Vaccines”: Lessons Learned from Clinical Trials, Mass Vaccination, and the Bio-Pharmaceutical Complex, Part 1

International Journal of Vaccine Theory Practice and Research, Journal Year: 2024, Volume and Issue: 3(2), P. 1112 - 1178

Published: June 29, 2024

Our understanding of COVID-19 synthetic, modified mRNA (modmRNA) products and their public health impact has evolved substantially since December 2020. Published reports from the original randomized placebo-controlled trials concluded that modmRNA injections could greatly reduce symptoms. However, premature termination both obviated any reliable assessment potential adverse events due to an insufficient timeframe for proper safety evaluation. Following authorization global distribution, problems with methods execution have emerged. The usual testing protocols toxicology requirements were bypassed. Many key trial findings either misreported or omitted entirely published reports. By implication, secondary estimates excess morbidity mortality in must be deemed underestimates. Rigorous re-analyses data post-marketing surveillance studies indicate a substantial degree modmRNA-related harms than was initially reported. Confidential Pfizer documents had revealed 1.6 million by August 2022. A third serious injuries cardiovascular, neurological, thrombotic, immunological, reproductive systems, along alarming increase cancers. Moreover, well-designed shown repeated cause immune dysfunction, thereby potentially contributing heightened susceptibility SARS-CoV-2 infections increased risks COVID-19. This paper also discusses insidious influence Bio-Pharmaceutical Complex, closely coordinated collaboration between organizations, pharmaceutical companies, regulatory agencies. We recommend moratorium on until toxicological are conducted.

Language: Английский

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Withdrawn: A systematic review of autopsy findings in deaths after COVID-19 vaccination

Forensic Science International, Journal Year: 2024, Volume and Issue: unknown, P. 112115 - 112115

Published: June 1, 2024

The rapid development of COVID-19 vaccines, combined with a high number adverse event reports, have led to concerns over possible mechanisms injury including systemic lipid nanoparticle (LNP) and mRNA distribution, Spike protein-associated tissue damage, thrombogenicity, immune system dysfunction, carcinogenicity. aim this systematic review is investigate causal links between vaccine administration death using autopsies post-mortem analysis. We searched PubMed ScienceDirect for all published autopsy necropsy reports relating vaccination up until May 18th, 2023. All studies that included as an antecedent exposure were included. Because the state knowledge has advanced since time original publications, three physicians independently reviewed each case adjudicated whether or not was direct cause contributed significantly death. initially identified 678 and, after screening our inclusion criteria, 44 papers contained 325 cases one case. mean age 70.4 years. most implicated organ among cardiovascular (49%), followed by hematological (17%), respiratory (11%), multiple systems (7%). Three more affected in 21 cases. from 14.3 days. Most deaths occurred within week last administration. A total 240 (73.9%) directly due vaccination, which primary causes include sudden cardiac (35%), pulmonary embolism (12.5%), myocardial infarction (12%), VITT (7.9%), myocarditis (7.1%), multisystem inflammatory syndrome (4.6%), cerebral hemorrhage (3.8%). consistency seen known death, coupled confirmation physician adjudication, suggests there likelihood link vaccines Further urgent investigation required purpose clarifying findings.

Language: Английский

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Risk stratification for future cardiac arrest after COVID-19 vaccination

World Journal of Cardiology, Journal Year: 2025, Volume and Issue: 17(2)

Published: Feb. 24, 2025

Unheralded cardiac arrest among previously healthy young people without antecedent illness, months or years after coronavirus disease 2019 (COVID-19) vaccination, highlights the urgent need for risk stratification. The most likely underlying pathophysiology is subclinical myopericarditis and reentrant ventricular tachycardia spontaneous fibrillation that commonly precipitated a surge in catecholamines during exercise waking hours of terminal sleep. Small patches inflammation and/or edema can be missed on imaging autopsy, heart appear grossly normal. This paper reviews evidence linking COVID-19 vaccines to where unfortunately majority victims have had no clinical evaluation. We propose comprehensive strategy evaluating cardiovascular post-vaccination, incorporating detailed patient history, antibody testing, diagnostics best attempt detect abnormalities before sudden death. approach aims identify individuals at higher events vaccination guide appropriate management. It prudent each primary care physician pre-established plan when addressing this issue their practice.

Language: Английский

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Eosinophils and COVID‐19: Insights into immune complexity and vaccine safety

Clinical and Translational Allergy, Journal Year: 2025, Volume and Issue: 15(3)

Published: March 1, 2025

Abstract Background COVID‐19 exhibits a variety of symptoms and may lead to multi‐organ failure death. This clinical complexity is exacerbated by significant immune dysregulation affecting nearly all cells the innate adaptive system. Granulocytes, including eosinophils, are affected SARS‐CoV‐2. Objectives Eosinophil responses remain poorly understood despite early recognition eosinopenia as hallmark feature severity. Results The heterogeneous nature eosinophil categorizes them dual‐function with contradictory effects. activation can suppress virus‐induced inflammation releasing type 2 cytokines like IL‐13 granular proteins antiviral action such eosinophil‐derived neurotoxins cationic protein, also acting antigen‐presenting cells. In contrast, accumulation in lungs induce tissue damage triggered or hormones IFN‐γ leptin. Additionally, they affect functions interacting T through direct formation membrane complexes soluble mediator action. Individuals allergic disorders who have elevated levels eosinophils tissues blood, asthma, do not appear be at an increased risk developing severe following SARS‐CoV‐2 infection. However, vaccine appears associated complications eosinophilic infiltrate‐induced immunopathogenicity, which mitigated corticosteroid, anti‐histamines anti‐IL‐5 therapy avoided modifying adjuvants excipients. Conclusion review highlights importance contributes better understanding their role during natural infection vaccination.

Language: Английский

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Considerations for mRNA Product Development, Regulation and Deployment Across the Lifecycle

Vaccines, Journal Year: 2025, Volume and Issue: 13(5), P. 473 - 473

Published: April 28, 2025

With the successful deployment of several mRNA vaccines against SARS-CoV-2, an vaccine RSV (respiratory syncytial virus) and a large pipeline products other infectious diseases, cancers rare it is important to examine whole product lifecycle. technology enables design, testing manufacturing systems be rapidly developed, but these advantages can lost if factors that determine public access are not closely considered. This review analyzes key aspects lifecycle including candidate manufacturing, quality safety storage. Regulatory thinking well advanced in some countries others, more thought on regulation outside pandemic situation as therapeutics individual neoantigen therapies disease treatments needed. Consumer acceptance—the “social license operate” around products—is critical for their uptake, particularly pandemic.

Language: Английский

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Fatal Myocarditis following COVID-19 mRNA Immunization: A Case Report and Differential Diagnosis Review

Vaccines, Journal Year: 2024, Volume and Issue: 12(2), P. 194 - 194

Published: Feb. 13, 2024

Carditis in childhood is a rare disease with several etiologies. We report case of infant death due to pericarditis and myocarditis after the mRNA vaccine against COVID-19 (COVIDmRNAV). A 7-year-old male child received first dose COVIDmRNAV presented monoarthritis fever non-responsive oral antibiotics. The laboratory investigation showed signs infection (leukocytosis, high levels c-reactive protein). His condition rapidly deteriorated, patient died. autopsy identified pericardial fibrin deposits, hemorrhagic areas myocardium, normal valves. diffuse intermyocardial inflammatory infiltrate composed T CD8+ lymphocytes histiocytes was identified. An antistreptolysin O (ASO) dosage titers. presence arthritis, elevated ASO, carditis fulfills criteria for rheumatic fever. However, valve Aschoff’s nodules, present 90% cases, were absent this case. temporal correlation vaccination prompted its inclusion as one In cases myocardial damage related COVID-19mRNAV, it appears be expression exosomes lipid nanoparticles, leading cytokine storm. potential effects COVID-19mRNAV must considered pathogenesis disease, whether an etiology or contributing factor previously initiated injury.

Language: Английский

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Excess Cardiopulmonary Arrest and Mortality after COVID-19 Vaccination in King County, Washington

Published: May 27, 2024

Background: Since the onset of widespread COVID-19 vaccination campaigns, there have been concerns about serious cardiovascular adverse events, including myocarditis, myocardial infarction, and venous thromboembolisms, all which can lead to cardiopulmonary arrest. This study aimed estimate excess arrest mortality in King County, WA, investigate any association with rates. Methods: Data was obtained from annual EMS reports, U.S. Census Bureau, The Tennessean Vaccine Tracker. An exploratory data analysis performed. Excess deaths were calculated using 2015-2020 trend line. relationship between rates analyzed polynomial regression analysis. A quadratic model used generate expected population growth trends. for County calculate yearly estimates fatalities USA. Results: Approximately 98% received at least one dose a vaccine by 2023. Our revealed 25.7% increase total arrests 25.4% 2020 2023 WA. estimated increased 1,236% 2023, rising 11 (95% CI: -12, 34) 147 123, 170) observed higher general sharply declined 0.94% (21,300) 2021, deviating size. Applying our these entire United States yielded 49,240 fatal 2021-2023. Conclusions: We identified very strong ecological temporal campaign, resulted high biological plausibility death acute cardiac pulmonary causes after has previously demonstrated is concerning given real-world observations. Urgent further research needed determine if similar trends are other regions attention risk mitigation incident events improved survival resuscitation.

Language: Английский

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