REVOLUTIONIZING CARDIOVASCULAR CRITICAL CARE: THE PROMISE OF PERSONALIZED THERAPIES BASED ON GENETIC PROFILING

: Cardiovascular diseases (CVDs) remain a leading cause of morbidity and mortality worldwide, necessitating innovative approaches to improve patient outcomes in critical care settings. The emergence of genomic medicine has opened new avenues for personalized therapies tailored to an individual's genetic profile. This narrative review not only explores the transformative potential of genetics-based customized medicine in cardiovascular critical care but also instills a sense of optimism about the future. We discuss the impact of genetic variations on disease development, prognosis, and therapeutic responses, highlighting the significance of gene profiling in risk stratification and treatment optimization. Furthermore, we delve into the evolving landscape of pharmacogenomics and its implications for individualized drug therapy in the intensive care unit. By embracing cutting-edge technologies such as gene editing and stem cell therapy, we envision a future where personalized medicine becomes the standard of care in cardiovascular critical care, ultimately improving patient outcomes and reducing the burden of CVDs.


INTRODUCTION
Cardiovascular diseases (CVDs) pose a significant challenge in critical care settings, accounting for a substantial proportion of morbidity and mortality in intensive care units (ICUs) worldwide [1].Despite advancements in medical technology and therapeutic interventions, the management of critically ill patients with CVDs remains complex and often suboptimal [2].The one-size-fits-all approach to treatment fails to account for everyone's 1 Molecular Dynamics and Modeling Laboratory (DynMolLab). 2UNIFOA. 3Faculdade Santa Marcelina. 4Santa Casa de Misericórdia de Vitoria Higher School of Sciences -EMESCAM Santa Luíza -Vitória -ES -Brazil Molecular Dynamics and Modeling Laboratory (DynMolLab) 5 Molecular Dynamics and Modeling Laboratory (DynMolLab) Santa Luíza -Vitória -ES -Brazil.
unique genetic makeup, leading to variable treatment responses and adverse outcomes [3].Reg genomic medicine has revolutionized our understanding of the genetic basis of CVDs, paving the way for personalized therapies tailored to an individual's genetic profile [4].This narrative review explores the transformative potential of genetics-based customized medicine in cardiovascular critical care, highlighting the latest advancements and prospects in this rapidly evolving field.

METHODOLOGY
A comprehensive literature search was conducted using multiple databases, including Scopus, Web of Science, PubMed, ScienceDirect, and JSTOR.The search terms included combinations of "cardiovascular diseases," "critical care," "intensive care," "personalized medicine," "genetic profiling," "pharmacogenomics," "gene editing," and "stem cell therapy." Relevant articles published in English between 2010 and 2023 were selected based on their scientific merit and contribution to the field of personalized medicine in cardiovascular critical care.The selected articles were critically appraised, and their findings were synthesized to provide a comprehensive overview of the current state of knowledge and future directions in this field.

Genetic Variations and CVD Risk Stratification in Critical Care:
Genetic variations are crucial in determining an individual's susceptibility to CVDs and their clinical outcomes in critical care settings [5].Genome-wide association studies (GWAS) have identified numerous genetic variants associated with an increased risk of developing CVDs, such as coronary artery disease (CAD), hypertrophic cardiomyopathy (HCM), and familial hypercholesterolemia [6,7].In the context of critical care, genetic profiling can aid in risk stratification, enabling the identification of high-risk patients who may require more intensive monitoring and targeted interventions [8].For example, genetic variants in the 9p21 locus have been associated with an increased risk of CAD and poor prognosis in patients admitted to the ICU with acute coronary syndromes [9].Incorporating genetic information into risk assessment algorithms can enhance the accuracy of risk prediction and guide personalized management strategies in the critical care setting [10].
Pharmacogenomics and Individualized Drug Therapy in the ICU: Pharmacogenomics, the study of how genetic variations influence drug response, holds immense promise for optimizing pharmacotherapy in the ICU [11].Critically ill patients often require multiple medications, including vasopressors, inotropes, antiarrhythmics, and anticoagulants, which can be associated with significant variability in efficacy and safety [12].
Genetic polymorphisms in drug-metabolizing enzymes, transporters, and targets can impact the pharmacokinetics and pharmacodynamics of these medications, leading to suboptimal treatment responses and adverse drug reactions [13].For instance, variations in the CYP2C19 gene have been shown to affect the metabolism and efficacy of clopidogrel, an antiplatelet agent commonly used in patients with acute coronary syndromes [14].Similarly, polymorphisms in the VKORC1 and CYP2C9 genes influence warfarin dosing requirements, necessitating personalized dosing algorithms to minimize bleeding complications [15].Implementing pharmacogenomic testing in the ICU can guide the selection and dosing of medications, reducing the risk of treatment failure and adverse events [16].

Gene Editing and Stem Cell Therapy for Cardiovascular Regeneration:
Gene editing technologies like CRISPR/Cas9 have become powerful tools for modifying disease-causing genes and restoring normal cellular function.In cardiovascular critical care, gene editing holds promise for treating genetic cardiomyopathies and other inherited cardiovascular disorders, offering a ray of hope for patients with these conditions.Preclinical studies have demonstrated the feasibility of gene editing to correct pathogenic mutations in cardiomyocytes, offering a potential therapeutic strategy for patients with endstage heart failure.Additionally, stem cell therapy and regenerative medicine are being explored as novel approaches to promote cardiovascular regeneration in critically ill patients.
Transplantation of autologous or allogeneic stem cells, such as mesenchymal stem cells or induced pluripotent stem cell-derived cardiomyocytes, has shown promise in improving cardiac function and reducing infarct size in animal models of myocardial infarction.While further research is needed to establish the safety and efficacy of these approaches in humans, gene editing and stem cell therapy represent exciting frontiers in personalized cardiovascular critical care.

Challenges and Future Directions:
Despite the immense potential of personalized medicine in cardiovascular critical care, several challenges must be addressed to facilitate its widespread adoption.These include the need for large-scale prospective studies to validate the clinical utility of genetic profiling and pharmacogenomic testing in the ICU setting.Additionally, integrating genomic data into electronic health records and developing decision support tools are essential to utilize genetic information in clinical practice effectively.Ethical considerations, such as informed consent, data privacy, and the potential for genetic discrimination, must also be carefully navigated.
Furthermore, the cost-effectiveness of implementing personalized medicine approaches in the ICU must be thoroughly evaluated to ensure their sustainability and accessibility.This discussion aims to highlight the urgency of addressing these challenges and the potential of emerging technologies, such as artificial intelligence and machine learning, to further advance personalized medicine in cardiovascular critical care.DISCUSSION Integrating personalized medicine into cardiovascular critical care holds immense promise for improving patient outcomes and reducing the burden of CVDs.By leveraging genetic profiling and pharmacogenomics, clinicians can tailor treatment strategies to an individual's unique genetic makeup, optimizing the efficacy and safety of therapeutic interventions.The advent of gene editing and stem cell therapy opens new avenues for treating genetic cardiovascular disorders and promoting cardiovascular regeneration in critically ill patients.However, successfully implementing personalized medicine in the ICU requires a concerted effort to address the associated challenges, including robust clinical validation, ethical considerations, and cost-effectiveness analyses.