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.

Takotsubo syndrome before and during the COVID-19 pandemic in Austria: a retrospective cohort study (TOSCA-19).

AIMS: This study aims to investigate the prevalence of Takotsubo syndrome (TTS) as a percentage of the total number of acute coronary syndrome (ACS), including non-STE-elevation myocardial infarction and ST-elevation myocardial infarction, as well as the short-term outcome of TTS patients before and during the COVID-19 pandemic. METHODS AND RESULTS: We compared patients from two different periods: (i) Period 1 (before the COVID-19 pandemic): 1 March to 30 December 2019, and (ii) Period 2 (during the COVID-19 pandemic): 1 March to 30 December 2020. The retrospective database was created from the archives of the participating hospitals or electronic hospital systems by trained medical personnel. The subjects' medical history, cardiovascular risk factors, laboratory values, echocardiography findings, and an in-hospital outcome were variables of interest. Furthermore, propensity score matching analysis was performed to evaluate the short-term prognosis in TTS and ACS patients. Altogether six Austrian centres-(i) 3rd Medical Department of Cardiology and Intensive Care Medicine, Clinic Ottakring, Vienna, Austria; (ii) 5th Medical Department of Cardiology, Clinic Favoriten, Vienna, Austria; (iii) 2nd Medical Department, Hanusch Hospital, Vienna, Austria; (iv) University Clinic of Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck, Austria; (v) Department of Cardiology, University Hospital Graz, Graz, Austria; (vi) Department of Cardiology and Intensive Medicine, Kepler University Clinic, Linz, Austria-participated in the study. During period 1, 87 (3.5%) patients out of 2482 ACS patients had TTS in all participating centres. During period 2, 71 (2.7%) patients out of 2572 ACS patients had TTS in all participating centres. Accordingly, the prevalence of TTS remained stable irrespective of potential psychologic stress during the COVID pandemic. Furthermore, the baseline characteristics of TTS patients did not change during the COVID-19 pandemic. The prevalence of in-hospital complications [cardiogenic shock (4.6% vs. 4.3%, P = 0.925), ventricle thrombus (1.1% vs. 1.4%, P = 0.885) and in-hospital bleeding (3.4% vs. 1.4%, P = 0.417)] remained stable. The all-cause in-hospital mortality of TTS patients did not change during the COVID-19 pandemic [χ2 (2) = 0.058, P = 0.810]. Moreover, a propensity score matching analysis of all-cause in-hospital mortality between matched TTS and ACS patients showed higher in-hospital mortality in ACS patients during COVID-19 pandemic (P = 0.043). CONCLUSIONS: Despite the well-known increased psychologic stress during the COVID-19 pandemic, the prevalence of TTS during the COVID-19 pandemic and the short-term clinical outcome in Austria remained unimpacted.

The LIPL study: Postprandial lipid profile, inflammation, and platelet activity in patients with chronic coronary syndrome.

Background and aims: It is suggested that the changes in atherosclerosis happen mainly under the influence of non-fasting lipids. To date, the studies in the postprandial state were primarily performed on healthy subjects. This exploratory, cross-sectional study investigates the change in lipid profile, inflammation, and platelet activation in patients with different cardiovascular risk profiles in the postprandial state. Methods: The studied population consists of 66 patients with different cardiovascular risks: patients with a history of the chronic coronary syndrome (CCS) and diabetes mellitus type 2 (DM2) (n = 20), CCS without DM2 (n = 25), and a healthy control group (n = 21). Lipid variables and markers of platelet function and inflammation were assessed during the fasting state and three and 5 h after a standardized fat meal using a standardized oral fat tolerance test (OFTT), a milkshake with 90 g of fat. Results: Patients with CCS and DM2 were significantly older and had the highest BMI. All patients with CCS were on acetylsalicylic acid, and 95% of CCS patients were on high-dose statins. The absolute leukocyte and neutrophile count increased significantly in the control group during the OFTT in comparison to CCS subjects. There was a significant decrease of HDL and increase of triglycerides during the OFTT, however with no difference between groups. There was no difference in the change of platelet activity between all groups. Conclusion: This study showed that OFTT leads to an increased postprandial inflammation response in healthy group compared to CCS ± DM2 while there was no change in lipid profile and platelet activity.

Data processing pipeline for cardiogenic shock prediction using machine learning.

Introduction: Recent advances in machine learning provide new possibilities to process and analyse observational patient data to predict patient outcomes. In this paper, we introduce a data processing pipeline for cardiogenic shock (CS) prediction from the MIMIC III database of intensive cardiac care unit patients with acute coronary syndrome. The ability to identify high-risk patients could possibly allow taking pre-emptive measures and thus prevent the development of CS. Methods: We mainly focus on techniques for the imputation of missing data by generating a pipeline for imputation and comparing the performance of various multivariate imputation algorithms, including k-nearest neighbours, two singular value decomposition (SVD)-based methods, and Multiple Imputation by Chained Equations. After imputation, we select the final subjects and variables from the imputed dataset and showcase the performance of the gradient-boosted framework that uses a tree-based classifier for cardiogenic shock prediction. Results: We achieved good classification performance thanks to data cleaning and imputation (cross-validated mean area under the curve 0.805) without hyperparameter optimization. Conclusion: We believe our pre-processing pipeline would prove helpful also for other classification and regression experiments.

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.

Neutrophile-Lymphocyte Ratio and Outcome in Takotsubo Syndrome.

Background: Takotsubo syndrome (TTS) is an important type of acute heart failure with significant risk of acute complications and death. In this analysis we sought to identify predictors for in-hospital clinical outcome in TTS patients and present long-term outcomes. Methods: In this analysis from the Austrian national TTS registry, univariable and multivariable analyses were performed to identify significant predictors for severe in-hospital complications requiring immediate invasive treatment or leading to irreversible damage, such as cardiogenic shock, intubation, stroke, arrhythmias and death. Furthermore, the influence of independent predictors on long-term survival was evaluated. Results: A total of 338 patients (median age 72 years, 86.9% female) from six centers were included. Severe in-hospital complications occurred in 14.5% of patients. In multivariable analysis, high neutrophile-lymphocyte-ratio (NLR; OR 1.04 [95% CI 1.02−1.07], p = 0.009) and low LVEF (OR 0.92 [0.90−0.95] per %, p < 0.001) were significant predictors of severe in-hospital complications. Both the highest NLR tercile and the lowest LVEF tercile were significantly associated with reduced 5-year survival. Conclusions: Low LVEF and high NLR at admission were independently associated with increased in-hospital complications and reduced long-term survival in TTS patients. NLR is a new easy-to-measure tool to predict worse short- and long-term outcome after TTS.

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.

Psychocardiological assessment in the acute phase of the takotsubo syndrome : Somatic and depressive disorders, resilience and illness perception.

OBJECTIVE: To analyze the psychocardiological profile and the clinical characteristics in the acute phase of takotsubo syndrome (TTS). METHODS: Prospective multicenter cohort study of TTS patients evaluating the clinical characteristics as well as the prevalence of somatic, depressive, panic, stress and anxiety disorders. Assessment of illness perception and resilience in the acute phase of the syndrome. RESULTS: All 27 evaluated TTS patients were female with a mean age of 68 years (±11.4 years). The apical type of TTS was found in 60% of patients, followed by the combined type of TTS in 30% of patients. Main clinical symptom leading to hospital admission was chest pain in nearly 80% of patients. An ST-segment elevation mimicking acute myocardial infarction was found in 44% of patients and T wave inversion in 26% of patients. An endogenous (emotional) stress event was found in 17 patients (63.0%), an exogenous (physical) stress event in 5 patients (18.5%) and a combined stress event in 2 patients (7.4%). In 11.1% of patients (n = 3) no stress event could be found. Moderate to high levels of illness threatening were found in 48% of patients and low to moderate resilience scores were found in 40% of patients. Somatic disorders were found in half of the patients (56%) followed by depressive disorders in 26% of patients. CONCLUSION: Moderate to low resilience scores and moderate to high levels of illness threatening can be seen in the acute phase of TTS, reflecting the severity of the experience as an adverse life event. Patients suffering from TTS present in the acute phase with a high prevalence of somatic disorders and relatively high prevalence of depressive disorders.

Long-term outcome in patients with takotsubo syndrome : A single center study from Vienna.

BACKGROUND: There is an increasing amount of evidence suggesting multiple fatal complications in takotsubo syndrome; however, findings on the long-term outcome are scarce and show inconsistent evidence. METHODS: This is a single center study of long-term prognosis in takotsubo patients admitted to the Klinik Ottakring, Vienna, Austria, from September 2006 to August 2019. We investigated the clinical features, prognostic factors and outcome of patients with takotsubo syndrome. Furthermore, survivors and non-survivors and patients with a different cause of death were compared. RESULTS: Overall, 147 patients were included in the study and 49 takotsubo patients (33.3%) died during the follow-up, with a median of 126 months. The most common cause of death was a non-cardiac cause (71.4% of all deaths), especially malignancies (26.5% of all deaths). Moreover, non-survivors were older and more often men with more comorbidities (chronic kidney disease, malignancy). Patients who died because of cardiovascular disease were older and more often women than patients who died due to non-cardiovascular cause. Adjusted analysis showed no feature of an independent predictor of cardiovascular mortality for takotsubo patients. Female gender (HR = 0.32, CI: 0.16-0.64, p < 0.001), cancer (HR = 2.35, CI: 1.15-4.8, p = 0.019) and chronic kidney disease (HR = 2.61, CI: 1.11-6.14, p = 0.028) showed to be independent predictors of non-cardiovascular mortality. CONCLUSION: Long-term prognosis of takotsubo patients is not favorable, mainly due to noncardiac comorbidities. Hence, consequent outpatient care in regular intervals after a takotsubo event based on risk factor control and early detection of malignancies seems justified.

Direct cardiovascular complications and indirect collateral damage during the COVID-19 pandemic : A review.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), puts a heavy strain on healthcare systems around the globe with high numbers of infected patients. Pre-existing cardiovascular disease is a major risk factor for a severe clinical course of COVID-19 and is associated with adverse outcome. COVID-19 may directly exacerbate underlying heart disease and is frequently aggravated by cardiovascular complications, including arterial and venous thromboembolic events, malignant arrhythmia and myocardial injury. In addition to these direct cardiac manifestations of COVID-19, patients with cardiovascular disease face further indirect consequences of the pandemic, as the respective resources in the healthcare systems need to be redirected to cope with the high numbers of infected patients. Consecutively, a substantial decrease in cardiac procedures was reported during the pandemic with lower numbers of coronary angiographies and device implantations worldwide. As a consequence an increased number of out-of-hospital cardiac arrests, late-comers with subacute myocardial infarction and of patients presenting in cardiogenic shock or preshock were observed. Maintenance of high-quality cardiac care by avoiding a reduction of cardiac services is of utmost importance, especially in times of a pandemic.