The intricate relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the cardiovascular system is an extensively studied pandemic topic, as there is an ever-increasing amount of evidence that reports a high prevalence of acute cardiac injury in the context of viral infection. In patients with Coronavirus disease 2019, COVID-19, a significant increase in serum levels of cardiac troponin or other various biomarkers was observed, suggesting acute cardiac injury, thus predicting both a severe course of the disease and a poor outcome. Pathogenesis of acute cardiac injury is not yet completely elucidated, though several mechanisms are allegedly involved, such as a direct cardiomyocyte injury, oxygen supply-demand inequity caused by hypoxia, several active myocardial depressant factors during sepsis, and endothelial dysfunction due to the hyperinflammatory status. Moreover, the increased levels of plasma cytokines and catecholamines and a significantly enhanced prothrombotic environment may lead to the destabilization and rupture of atheroma plaques, subsequently triggering an acute coronary syndrome. In the present review, we focus on describing the epidemiology, pathogenesis, and role of biomarkers in the diagnosis and prognosis of patients with acute cardiac injury in the setting of the COVID-19 pandemic. We also explore some novel therapeutic strategies involving immunomodulatory therapy, as well as their role in preventing a severe form of the disease, with both the short-term outcome and the long-term cardiovascular sequelae being equally important in patients with SARS-CoV-2 induced acute cardiac injury.

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A Real Pandora’s Box in Pandemic Times: A Narrative Review on the Acute Cardiac Injury Due to COVID-19

A phytochemical investigation of the n-hexane-soluble chemical constituents ofLysimachia vulgaris roots allowed for selection using a proprotein convertase subtilisin-kexin type 9 (PCSK9) mRNA expression monitoring assay in HepG2 cells. This led to the isolation of two previously undescribed isocoumarins of natural origin, 8′Z,11′Z-octadecadienyl-6,8-dihydroxyisocoumarin (1) and 3-pentadecyl-6,8-dihydroxyisocoumarin (2), along with 20 previously reported compounds (3–22). All of the structures were established using NMR spectroscopic data and MS analysis. Of the isolates, 1 and 3 were found to inhibit PCSK9, inducible degrader of the low-density lipoprotein receptor (IDOL), and SREBP2 mRNA expression. Further computational dockings of both 1 and 3 to C-ring of IDOL E3 ubiquitin ligase predicted the mechanism behind the inhibitory effect of these compounds on the enzyme.

Isocoumarins and Benzoquinones with Their Proprotein Convertase Subtilisin/Kexin Type 9 Expression Inhibitory Activities from Dried Roots of Lysimachia vulgaris

Background: Data regarding the combined prognostic role of biomarkers and risk scores in relation with the history of atherosclerotic cardiovascular disease (ASCVD) in COVID-19 patients are lacking. Methods: The aim of this observational cohort study was to evaluate the combined prognostic value of N-terminal pro B-type natriuretic peptide (NT-pro BNP), troponin and risk scores in relation with ASCVD history in hospitalized COVID-19 patients. The primary composite endpoint was Intensive Care Unit (ICU) admission and death. Results: From April 2020 to June 2022, 1066 consecutive COVID-19 patients with available biomarkers upon admission were included. During a median follow-up period of 12 days, 176 patients (16.5%) died. Independent predictors of ICU admission and death in patients with ASCVD were NT-pro BNP (HR 2.63; 95% CI, 1.65–4.18) and troponin (HR 1.51; 95% CI, 1.13–2.03). In patients without ASCVD, only NT-pro BNP was predictive for the primary endpoint (HR 1.66; 95% CI, 1.10–2.53). This remained significant after adjustment for other relevant covariates (HR 3.54; 95% CI, 1.98–6.33) in patients with ASCVD and in patients without ASCVD (HR 1.82; 95% CI, 1.02–3.26). Conclusions: These data showed the combined prognostic accuracy of NT-pro BNP and troponin in relation with ASCVD history for ICU admission and death in COVID-19 patients.

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Cardiac Biomarkers and Risk Scores in Relation with History of Atherosclerotic Cardiovascular Disease in Patients Admitted with COVID-19: The Experience of an Eastern European Center

Effectiveness and safety of Inclisiran in hyperlipidemia treatment: An overview of systematic reviews

Coronavirus disease-19 (COVID-19) emerged late December 2019 in the city of Wuhan, China and has since spread rapidly all over the world causing a global pandemic. While the respiratory system is the primary target of disease manifestation, COVID-19 has been shown to also affect several other organs, making it a rather complex, multi-system disease. As such, cardiovascular involvement has been a topic of discussion since the beginning of the COVID-19 pandemic, primarily due to early reports of excessive myocardial injury in these patients. Treating physicians are faced with multiple challenges in the management and early triage of patients with COVID-19, as disease severity is highly variable ranging from an asymptomatic infection to critical cases rapidly deteriorating to intensive care treatment or even fatality. Laboratory biomarkers provide important prognostic information which can guide decision making in the emergency department, especially in patients with atypical presentations. Several cardiac biomarkers, most notably high-sensitive cardiac troponin (hs-cTn) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), have emerged as valuable predictors of prognosis in patients with COVID-19. The purpose of this review was to offer a concise summary on prognostic cardiac biomarkers in COVID-19 and discuss whether routine measurements of these biomarkers are warranted upon hospital admission.

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Biomarkers Associated with Cardiovascular Disease in COVID-19

The effective and fast reduction of circulating low-density lipoprotein cholesterol (LDL-C) is a cornerstone for secondary prevention of atherosclerotic disease progression. Despite the substantial lipid-lowering effects of the established treatment option with statins and ezetimibe, a significant proportion of very-high-risk patients with cardiovascular disease do not reach the recommended treatment goal of <55 mg/dL (<1.4 mmol/L). Novel lipid-lowering agents, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies alirocumab and evolocumab, the small interfering ribonucleotide acid (si-RNA) inclisiran, as well as the recently approved bempedoic acid, now complete the current arsenal of LDL-C lowering agents. These innovative therapies have demonstrated promising results in clinical studies. Besides a strong reduction of LDL-C by use of highly effective agents, there is still discussion as to whether a very rapid achievement of the treatment goal should be a new strategic approach in lipid-lowering therapy. In this review, we summarize evidence for the lipid-modifying properties of these novel agents and their safety profiles, and discuss their potential pleiotropic effects beyond LDL-C reduction (if any) as well as their effects on clinical endpoints as cardiovascular mortality. In addition to a treatment strategy of “the lower, the better”, we also discuss the concept of “the earlier, the better”, which may also add to the early clinical benefit of large LDL-C reduction after an acute ischemic event.

https://www.mdpi.com/2227-9059/10/5/970/pdf?version=1650607857

New Treatment Targets and Innovative Lipid-Lowering Therapies in Very-High-Risk Patients with Cardiovascular Disease

Background: Excess cardiovascular (CV) morbidity and mortality has been observed in patients with COVID-19. Both interleukin-32 (IL-32) and interleukin-34 (IL-34) have been hypothesized to contribute to CV involvement in COVID-19. Methods: This prospective, observational study of patients with laboratory-confirmed COVID-19 infection was conducted from 6 June to 22 December 2020 in a tertiary care hospital in Vienna, Austria. IL-32 and IL-34 levels on admission were collected and tested for their association with CV disease and short-term mortality in patients with COVID-19. CV disease was defined by the presence of coronary artery disease, heart failure, stroke or atrial fibrillation and patients were stratified by CV disease burden. Results: A total of 245 eligible patients with COVID-19 were included, of whom 37 (15.1%) reached the primary endpoint of 28-day mortality. Of the total sample, 161 had no CV disease (65.7%), 69 had one or two CV diseases (28.2%) and 15 patients had ≥three CV diseases (6.1%). Median levels of IL-32 and IL-34 at admission were comparable across the three groups of CV disease burden. IL-32 and IL-34 failed to predict mortality upon both univariable and multivariable Cox regression analysis. The two CV disease groups, however, had a significantly higher risk of mortality within 28 days (one or two CV diseases: crude HR 4.085 (95% CI, 1.913–8.725), p < 0.001 and ≥three CV diseases: crude HR 13.173 (95% CI, 5.425–31.985), p < 0.001). This association persisted for those with ≥three CV diseases after adjustment for age, gender and CV risk factors (adjusted HR 3.942 (95% CI, 1.288–12.068), p = 0.016). Conclusion: In our study population of hospitalized patients with COVID-19, IL-32 and IL-34 did not show any associations with CV disease or 28-day mortality in the context of COVID-19. Patients with multiple CV diseases, however, had a significantly increased risk of short-term mortality.

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Association of Interleukin-32 and Interleukin-34 with Cardiovascular Disease and Short-Term Mortality in COVID-19

Dual antiplatelet therapy (DAPT) for 6–12 months, followed by lifelong aspirin monotherapy is considered an effective standard therapy for the prevention of thrombo-ischemic events in patients with acute and chronic coronary syndrome (ACS, CCS) undergoing percutaneous coronary intervention (PCI) or after a primarily conservative treatment decision. In ACS patients, the stronger P2Y12-inhibitors ticagrelor or prasugrel are recommended in combination with aspirin unless the individual bleeding risk is high and shortening of DAPT is warranted or clopidogrel is preferred. However, also in patients at low individual bleeding risk, DAPT is associated with a higher risk of bleeding. In recent years, new antithrombotic treatment strategies, such as shortening DAPT followed by early P2Y12-inhibitor monotherapy and de-escalating DAPT from potent P2Y12-inhibitors to clopidogrel by maintaining DAPT duration time, have been investigated in clinical trials and shown to reduce bleeding complications in cardiovascular high-risk patients without negative effects on ischemic events. In this review, we summarize the current knowledge and discuss its implication on future antithrombotic strategies in terms of a personalized medicine.

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Short dual antiplatelet therapy and dual antiplatelet therapy de-escalation after primary percutaneous intervention: For whom and how

Recommendation on the use of cardiac biomarkers in the ESC guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery: challenges and opportunities. Perioperative myo cardial injury (PMI) is a common complication after non-cardiac surgery and is associated with a high postoperative mortality. The current ESC guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery recommend routine perioperative troponin surveillance in selected patients at risk for cardiovascular events undergoing intermediateand high-risk surgeries to detect PMI. Measurement of preoperative baseline troponin levels are necessary to differentiate PMI from chronic myocardial injury. According to current guidelines, a diagnosis of PMI is made if troponin levels are elevated with a dynamic change (troponin rise of more than the upper limit of normal, which is 14 ng/L for high-sensitivity Troponin T). As postoperative mortality is elevated in patients with and without additional symptoms suggestive of myocardial ischemia, the diagnosis of PMI is solely based on troponin levels (as opposed to the diagnosis of acute myocardial infarction). The causes of PMI are hetero geneous and patients with PMI need a systematic work-up and treatment according to the underlying cause. An interdisciplinary approach is mandatory for the implementation of PMI screening. J Kardiol 2023; 30 (5–6): 132–7.

Empfehlung zum Einsatz kardialer Biomarker in der ESC-Leitlinie für perioperatives Management von Patienten bei nicht-kardiochirurgischen Operationen: Herausforderungen und Chancen //Recommendation on the use of cardiac biomarkers in ESC guidelines

Marie Muthspiel

Papers

Biomarkers Associated with Cardiovascular Disease in COVID-19

New Treatment Targets and Innovative Lipid-Lowering Therapies in Very-High-Risk Patients with Cardiovascular Disease

Association of Interleukin-32 and Interleukin-34 with Cardiovascular Disease and Short-Term Mortality in COVID-19

Short dual antiplatelet therapy and dual antiplatelet therapy de-escalation after primary percutaneous intervention: For whom and how

Empfehlung zum Einsatz kardialer Biomarker in der ESC-Leitlinie für perioperatives Management von Patienten bei nicht-kardiochirurgischen Operationen: Herausforderungen und Chancen //Recommendation on the use of cardiac biomarkers in ESC guidelines