Impact of an Ultra-Endurance Marathon on Cardiac Function in Association with Cardiovascular Biomarkers.

BACKGROUND: Participation in ultra-endurance races may lead to a transient decline in cardiac function and increased cardiovascular biomarkers. This study aims to assess alterations in biventricular function immediately and five days after the competition in relation to elevation of high-sensitivity cardiac Troponin I (hs-cTnI) and N-terminal-pro-brain-natriuretic-peptide (NT-proBNP). METHODS AND RESULTS: Fifteen participants of an ultramarathon (UM) with a running distance of 130 km were included. Transthoracic echocardiography and quantification of biomarkers was performed before, immediately after and five days after the race. A significant reduction in right ventricular fractional area change (FAC) was observed after the race (48.0 ± 4.6% vs. 46.7 ± 3.8%, p = 0.011) that persisted five days later (48.0 ± 4.6% vs. 46.3 ± 3.9%, p = 0.027). No difference in left ventricular ejection fraction (LVEF) was found (p = 0.510). Upon stratification according to biomarkers, participants with NT-proBNP above the median had a significantly reduced LVEF directly (60.8 ± 3.6% vs. 56.9 ± 4.8%, p = 0.030) and five days after the race (60.8 ± 3.6% vs. 55.3 ± 4.5%, p = 0.007) compared to baseline values. FAC was significantly reduced five days after the race (48.4 ± 5.1 vs. 44.3 ± 3.9, p = 0.044). Athletes with hs-cTnI above the median had a significantly reduced FAC directly after the race (48.1 ± 4.6 vs. 46.5 ± 4.4, p = 0.038), while no difference in LVEF was observed. No alteration in cardiac function was observed if hs-cTnI or NT-proBNP was below the median. CONCLUSION: A slight decline in cardiac function after prolonged strenuous exercise was observed in athletes with an elevation of hs-cTnI and NT-proBNP above the median but not below.

Lipid-Lowering Therapy after Acute Coronary Syndrome.

Achieving guideline-recommended low-density lipoprotein cholesterol (LDL-C) targets remains a significant challenge in clinical practice. This review assesses the barriers to reaching LDL-C goals and explores the potential solutions to these issues. When aiming for the recommended LDL-C goal, strategies like "lower is better" and "strike early and strong" should be used. The evidence supports the safety and efficacy of intensive lipid-lowering therapy post-acute coronary syndrome (ACS), leading to improved long-term cardiovascular health and atherosclerotic plaque stabilization. Despite the availability of effective lipid-lowering therapies, such as high-intensity statins, ezetimibe, the combination of both, bempedoic acid, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a substantial proportion of patients do not meet their LDL-C targets. Contributing factors include systemic healthcare barriers, healthcare provider inertia, patient non-adherence, and statin intolerance. Statin intolerance, often rather statin reluctance, is a notable obstacle due to perceived or expected side effects, which can lead to discontinuation of therapy. In conclusion, while there are obstacles to achieving optimal LDL-C levels post-ACS, these can be overcome with a combination of patient-centric approaches, clinical vigilance, and the judicious use of available therapies. The safety and necessity of reaching lower LDL-C goals to improve outcomes in patients post-ACS are well-supported by current evidence.

Antiplatelet Therapy and Anticoagulation before, during, and after Acute Coronary Syndrome.

Acute coronary syndrome (ACS) remains a major challenge in clinical practice, requiring rapid and effective antithrombotic treatment to mitigate adverse ischemic events while minimizing the risk of bleeding. In recent years, results from several clinical trials addressing this issue through various approaches have substantially improved the treatment landscape for patients presenting with ACS. The emergence of new, potent P2Y12 inhibitors has significantly enhanced thrombotic risk reduction and different strategies for de-escalating and shortening dual antiplatelet therapy (DAPT) have demonstrated promising outcomes in reducing bleeding rates. Furthermore, data from ongoing trials focusing on novel therapeutic agents and investigating alternative treatment strategies to optimize outcomes for ACS patients are expected in the next few years. In this review, we summarize the current knowledge and emphasize the critical role of individualized treatment approaches tailored to patient-specific risk factors and individual clinical scenarios.

Low-density lipoprotein cholesterol reduction with immediate combination therapy of statin and ezetimibe compared to statin monotherapy after percutaneous coronary intervention.

BACKGROUND: Current guidelines recommend a stepwise initiation of lipid-lowering therapy after percutaneous coronary interventions (PCI) in treatment-naïve individuals. Patients might benefit from an earlier and stronger low-density lipoprotein-cholesterol (LDL-C) reduction through upfront combination therapies. METHODS: This retrospective study included patients without previous lipid-lowering therapy undergoing acute or elective PCI with stent implantation between January 2016 and December 2019. Patients initiated on statin monotherapy vs. a combination of statin and ezetimibe were compared. The primary endpoint was an LDL­C reduction into the target range of < 55 mg/dL at 3 months. The secondary endpoint was the occurrence of major cardiovascular events (MACE). RESULTS: A total of 204 lipid-lowering therapy naive patients were included, of whom 157 (77.0%) received statin monotherapy and 47 (23.0%) combination therapy. Median LDL­C levels were higher in patients initiated on combination therapy vs. monotherapy (140 mg/dL, interquartile range, IQR, 123-167 mg/dL vs. 102 mg/dL, IQR 80-136 mg/dL, p < 0.001). The LDL­C reduction was greater in patients treated with combination therapy vs. statin monotherapy (-73 mg/dL, -52.1% vs. -43 mg/dL, -42.2%, p < 0.001). While the primary endpoint was similar between groups (44.7% vs. 36.1%, p = 0.275), combination therapy significantly increased the proportion of patients achieving the treatment target in the presence of an admission LDL-C > 120 mg/dL (46.2% vs. 26.2%, p = 0.031). The rates of MACE were similar between the two groups (10.6% vs. 17.8%, p = 0.237) at a median follow-up of 2.2 years, IQR 1.46-3.10 years. CONCLUSION: Immediate initiation of high-intensity statin and ezetimibe treatment might be considered as the default strategy in treatment-naïve patients with high admission LDL­C undergoing PCI.

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

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.

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

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.

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

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.

Biomarkers Associated with Cardiovascular Disease in COVID-19.

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.