A Second Space Age Spanning Omics, Platforms, and Medicine Across Orbits.

The recent acceleration of commercial, private, and multi-national spaceflight has created an unprecedented level of activity in low Earth orbit (LEO), concomitant with the highest-ever number of crewed missions entering space and preparations for exploration-class (>1 year) missions. Such rapid advancement into space from many new companies, countries, and space-related entities has enabled a"Second Space Age." This new era is also poised to leverage, for the first time, modern tools and methods of molecular biology and precision medicine, thus enabling precision aerospace medicine for the crews. The applications of these biomedical technologies and algorithms are diverse, encompassing multi-omic, single-cell, and spatial biology tools to investigate human and microbial responses to spaceflight. Additionally, they extend to the development of new imaging techniques, real-time cognitive assessments, physiological monitoring, and personalized risk profiles tailored for astronauts. Furthermore, these technologies enable advancements in pharmacogenomics (PGx), as well as the identification of novel spaceflight biomarkers and the development of corresponding countermeasures. In this review, we highlight some of the recent biomedical research from the National Aeronautics and Space Administration (NASA), Japan Aerospace Exploration Agency (JAXA), European Space Agency (ESA), and other space agencies, and also detail the commercial spaceflight sector's (e.g. SpaceX, Blue Origin, Axiom, Sierra Space) entrance into aerospace medicine and space biology, the first aerospace medicine biobank, and the myriad upcoming missions that will utilize these tools to ensure a permanent human presence beyond LEO, venturing out to other planets and moons.

Hypertrophic cardiomyopathy is characterized by alterations of the mitochondrial calcium uniporter complex proteins: insights from patients with aortic valve stenosis versus hypertrophic obstructive cardiomyopathy.

Introduction: Hypertrophies of the cardiac septum are caused either by aortic valve stenosis (AVS) or by congenital hypertrophic obstructive cardiomyopathy (HOCM). As they induce cardiac remodeling, these cardiac pathologies may promote an arrhythmogenic substrate with associated malignant ventricular arrhythmias and may lead to heart failure. While altered calcium (Ca2+) handling seems to be a key player in the pathogenesis, the role of mitochondrial calcium handling was not investigated in these patients to date. Methods: To investigate this issue, cardiac septal samples were collected from patients undergoing myectomy during cardiac surgery for excessive septal hypertrophy and/or aortic valve replacement, caused by AVS and HOCM. Septal specimens were matched with cardiac tissue obtained from post-mortem controls without cardiac diseases (Ctrl). Results and discussion: Patient characteristics and most of the echocardiographic parameters did not differ between AVS and HOCM. Most notably, the interventricular septum thickness, diastolic (IVSd), was the greatest in HOCM patients. Histological and molecular analyses showed a trend towards higher fibrotic burden in both pathologies, when compared to Ctrl. Most notably, the mitochondrial Ca2+ uniporter (MCU) complex associated proteins were altered in both pathologies of left ventricular hypertrophy (LVH). On the one hand, the expression pattern of the MCU complex subunits MCU and MICU1 were shown to be markedly increased, especially in AVS. On the other hand, PRMT-1, UCP-2, and UCP-3 declined with hypertrophy. These conditions were associated with an increase in the expression patterns of the Ca2+ uptaking ion channel SERCA2a in AVS (p = 0.0013), though not in HOCM, compared to healthy tissue. Our data obtained from human specimen from AVS or HOCM indicates major alterations in the expression of the mitochondrial calcium uniporter complex and associated proteins. Thus, in cardiac septal hypertrophies, besides modifications of cytosolic calcium handling, impaired mitochondrial uptake might be a key player in disease progression.

Prophylactic rivaroxaban in the early post-discharge period reduces the rates of hospitalization for atrial fibrillation and incidence of sudden cardiac death during long-term follow-up in hospitalized COVID-19 survivors.

Introduction: While acute Coronavirus disease 2019 (COVID-19) affects the cardiovascular (CV) system according to recent data, an increased CV risk has been reported also during long-term follow-up (FU). In addition to other CV pathologies in COVID-19 survivors, an enhanced risk for arrhythmic events and sudden cardiac death (SCD) has been observed. While recommendations on post-discharge thromboprophylaxis are conflicting in this population, prophylactic short-term rivaroxaban therapy after hospital discharge showed promising results. However, the impact of this regimen on the incidence of cardiac arrhythmias has not been evaluated to date. Methods: To investigate the efficacy of this therapy, we conducted a single center, retrospective analysis of 1804 consecutive, hospitalized COVID-19 survivors between April and December 2020. Patients received either a 30-day post-discharge thromboprophylaxis treatment regimen using rivaroxaban 10 mg every day (QD) (Rivaroxaban group (Riva); n = 996) or no thromboprophylaxis (Control group (Ctrl); n = 808). Hospitalization for new atrial fibrillation (AF), new higher-degree Atrioventricular-block (AVB) as well as incidence of SCD were investigated in 12-month FU [FU: 347 (310/449) days]. Results: No differences in baseline characteristics (Ctrl vs Riva: age: 59.0 (48.9/66.8) vs 57 (46.5/64.9) years, p = n.s.; male: 41.5% vs 43.7%, p = n.s.) and in the history of relevant CV-disease were observed between the two groups. While hospitalizations for AVB were not reported in either group, relevant rates of hospitalizations for new AF (0.99%, n = 8/808) as well as a high rate of SCD events (2.35%, n = 19/808) were seen in the Ctrl. These cardiac events were attenuated by early post-discharge prophylactic rivaroxaban therapy (AF: n = 2/996, 0.20%, p = 0.026 and SCD: n = 3/996, 0.30%, p < 0.001) which was also observed after applying a logistic regression model for propensity score matching (AF: χ 2-statistics = 6.45, p = 0.013 and SCD: χ 2-statistics = 9.33, p = 0.002). Of note, no major bleeding complications were observed in either group. Conclusion: Atrial arrhythmic and SCD events are present during the first 12 months after hospitalization for COVID-19. Extended prophylactic Rivaroxaban therapy after hospital discharge could reduce new onset of AF and SCD in hospitalized COVID-19 survivors.

Effects of Angiotensin Receptor-Neprilysin Inhibitors (ARNIs) on the Glucose and Fat Metabolism Biomarkers Leptin and Fructosamine.

(1) Background: Heart failure with reduced ejection fraction (HFrEF) remains a major health burden. Angiotensin-Receptor-Neprilysin-Inhibitors (ARNIs) are an established HFrEF therapy which increases natriuretic peptide levels by inhibiting neprilysin. Leptin is a lipid metabolism parameter, which is also involved in glucose metabolism and is suggested to correlate with HF burden. While the hormone also seems to interact with neprilysin, potential associations with ARNI therapy have not been investigated yet. (2) Methods: To study this issue, we measured levels of leptin and fructosamine in consecutive 72 HFrEF patients before initiation of ARNI therapy and 3-6 months after initiation of therapy in two European centers. Biomarker levels were correlated with clinical parameters including ejection fraction, LVEF, and NYHA class. (3) Results: During a follow-up of up to 6 months, clinical parameters improved significantly (LVEF: 30.2 ± 7.8% to 37.6 ± 10.0%, (p < 0.001) and a significant improvement of the mean NYHA class with initial 32 patients in NYHA III or IV and 8 patients in NYHA class III/IV during the follow up (p < 0.001). The initial NT-proBNP levels of 2251.5 ± 2566.8 pg/mL significantly improved to 1416.7 ± 2145 pg/mL, p = 0.008) during follow up. ARNI therapy was also associated with an increase in leptin levels (17.5 ± 23.4 µg/L to 22.9 ± 29.3, p < 0.001) and furthermore, affected glucose metabolism indicated by elevation of fructosamine values (333.9 ± 156.8 µmol/L to 454.8 ± 197.8 µmol/L, p = 0.013). (4) Conclusion: while in the early phase of therapy, ARNI promotes clinical improvement of HFrEF, and it also seems to affect fat and glucose parameters, indicating significant metabolic implications of this therapy regime.

Impact of cavotricuspid isthmus ablation for typical atrial flutter and heart failure in the elderly-results of a retrospective multi-center study.

Introduction: While in the CASTLE-AF trial, in patients with atrial fibrillation and heart failure with reduced ejection fraction, interventional therapy using pulmonary vein isolation was associated with outcome improvement, data on cavotricuspid isthmus ablation (CTIA) in atrial flutter (AFL) in the elderly is rare. Methods: We included 96 patients between 60 and 85 years with typical AFL and heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF) treated in two medical centers. 48 patients underwent an electrophysiological study with CTIA, whereas 48 patients received rate or rhythm control and guideline-compliant heart failure therapy. Patients were followed up for 2 years, with emphasis on left ventricular ejection fraction (LVEF) over time. Primary endpoints were cardiovascular mortality and hospitalization for cardiac causes. Results: Patients with CTIA showed a significant increase in LVEF after 1 (p < 0.001) and 2 years (p < 0.001) in contrast to baseline LVEF. Improvement of LVEF in the CTIA group was associated with significantly lower 2-year mortality (p = 0.003). In the multivariate regression analysis, CTIA remained the relevant factor associated with LVEF improvement (HR: 2.845 CI:95% 1.044-7.755; p = 0.041). Elderly patients (≥ 70 years) further benefited from CTIA, since they showed a significantly reduced rehospitalization (p = 0.042) and mortality rate after 2 years (p = 0.013). Conclusions: CTIA in patients with typical AFL and HFrEF/HFmrEF was associated with significant improvement of LVEF and reduced mortality rates after 2 years. Patient age should not be a primary exclusion criterion for CTIA, since patients ≥70 years also seem to benefit from intervention in terms of mortality and hospitalization.

Rational and design of the REMOTE trial: An exploratory, pilot study to analyze REtinal MicrOcirculaTion in wEightlessness.

BACKGROUND: "Spaceflight associated neuro-ocular syndrome" (SANS) represents a challenging health condition in modern space medicine. Forty-eight percent of astronauts are diagnosed with SANS after long-term space missions. The pathophysiological mechanism seems to be multifactorial, and yet remains unknown. In this proof-of-concept study we plan to investigate retinal microcirculatory changes in weightlessness and aim to identify their role in the development of SANS. METHODS AND DESIGN: Healthy individuals will take part in a parabolic flight campaign, which recreates fractioned total weightlessness periods. The airplane is specifically equipped, and designed for the execution of parabolic flight maneuvers and scientific research in microgravity. Retinal microcirculation will be assessed with a modified fundus camera, which allows dynamic vessel analysis. We will additionally measure intra-ocular pressure and hemodynamic changes during each phase of the flight. Blood samples will be analyzed at baseline, one hour and 24 hours after exposure to weightlessness. CONCLUSIONS: This pilot study aims to investigate the feasibility of retinal microcirculation assessment during varying gravity. Results of this study may generate insights whether venous stasis in the eye, surrogated by the dilatation of retinal vessels and increase in intraocular pressure as signs of venous insufficiency, may potentially contribute to the development of SANS.

Investigation of hs-TnI and sST-2 as Potential Predictors of Long-Term Cardiovascular Risk in Patients with Survived Hospitalization for COVID-19 Pneumonia.

Introduction: COVID-19 survivors reveal an increased long-term risk for cardiovascular disease. Biomarkers like troponins and sST-2 improve stratification of cardiovascular risk. Nevertheless, their prognostic value for identifying long-term cardiovascular risk after having survived COVID-19 has yet to be evaluated. Methods: In this single-center study, admission serum biomarkers of sST-2 and hs-TnI in a single cohort of 251 hospitalized COVID-19 survivors were evaluated. Concentrations were correlated with major cardiovascular events (MACE) defined as cardiovascular death and/or need for cardiovascular hospitalization during follow-up after hospital discharge [FU: 415 days (403; 422)]. Results: MACE was a frequent finding during FU with an incidence of 8.4% (cardiovascular death: 2.8% and/or need for cardiovascular hospitalization: 7.2%). Both biomarkers were reliable indicators of MACE (hs-TnI: sensitivity = 66.7% & specificity = 65.7%; sST-2: sensitivity = 33.3% & specificity = 97.4%). This was confirmed in a multivariate proportional-hazards analysis: besides age (HR = 1.047, 95% CI = 1.012−1.084, p = 0.009), hs-TnI (HR = 4.940, 95% CI = 1.904−12.816, p = 0.001) and sST-2 (HR = 10.901, 95% CI = 4.509−29.271, p < 0.001) were strong predictors of MACE. The predictive value of the model was further improved by combining both biomarkers with the factor age (concordance index hs-TnI + sST2 + age = 0.812). Conclusion: During long-term FU, hospitalized COVID-19 survivors, hs-TnI and sST-2 at admission, were strong predictors of MACE, indicating both proteins to be involved in post-acute sequelae of COVID-19.

Early antithrombotic post-discharge therapy using prophylactic DOAC or dipyridamole improves long-term survival and cardiovascular outcomes in hospitalized COVID-19 survivors.

Introduction: Cardiovascular events are common in COVID-19. While the use of anticoagulation during hospitalization has been established in current guidelines, recommendations regarding antithrombotic therapy in the post-discharge period are conflicting. Methods: To investigate this issue, we conducted a retrospective follow-up (393 ± 87 days) of 1,746 consecutive patients, hospitalized with and surviving COVID-19 pneumonia at a single tertiary medical center between April and December 2020. Survivors received either 30-day post-discharge antithrombotic treatment regime using prophylactic direct oral anticoagulation (DOAC; n = 1,002) or dipyridamole (n = 304), or, no post-discharge antithrombotic treatment (Ctrl; n = 440). All-cause mortality, as well as cardiovascular mortality (CVM) and further cardiovascular outcomes (CVO) resulting in hospitalization due to pulmonary embolism (PE), myocardial infarction (MI) and stroke were investigated during the follow-up period. Results: While no major bleeding events occured during follow-up in the treatment groups, Ctrl showed a high but evenly distributed rate all-cause mortality. All-cause mortality (CVM) was attenuated by prophylactic DOAC (0.6%, P < 0.001) and dipyridamole (0.7%, P < 0.001). This effect was also evident for both therapies after propensity score analyses using weighted binary logistic regression [DOAC: B = -3.33 (0.60), P < 0.001 and dipyridamole: B = -3.04 (0.76), P < 0.001]. While both treatment groups displayed a reduced rate of CVM [DOAC: B = -2.69 (0.74), P < 0.001 and dipyridamole: B = -17.95 (0.37), P < 0.001], the effect in the DOAC group was driven by reduction of both PE [B-3.12 (1.42), P = 0.012] and stroke [B = -3.08 (1.23), P = 0.028]. Dipyridamole significantly reduced rates of PE alone [B = -17.05 (1.01), P < 0.001]. Conclusion: Late cardiovascular events and all-cause mortality were high in the year following hospitalization for COVID-19. Application of prophylactic DOAC or dipyridamole in the early post-discharge period improved mid- and long-term CVO and all-cause mortality in COVID-19 survivors.

Impact of socioeconomic aspects on cardiac implantable electronic device treatment and application of the EHRA guidelines : A European comparison.

BACKGROUND: Cardiac implantable electronic devices (CIED) have become an indispensable part in everyday clinical practice in cardiology. The indications for CIED implantation are based on the guidelines of the European Heart Rhythm Association (EHRA). Nevertheless, numbers of CIED implantations in Europe are subject to considerable differences. We hypothesized that reimbursements linked to the respective health systems may influence implantation behavior. METHODS: Based on the EHRA White Book 2017, CIED implantation data as well as socioeconomic key figures were collected, in particular gross domestic product (GDP) and share of gross domestic product spent on healthcare. Implantation numbers for pacemakers, implantable cardioverter defibrillators and cardiac resynchronization treatment as well as all in total were assessed, compared with the health care expenditures and visualized using heat maps. RESULTS: Total implantation numbers per 100,000 inhabitants varied from 196.53 (Germany) to 2.81 (Kosovo). Higher implantation numbers correlated moderately with a higher GDP (r = 0.456, p 0.002) and higher health expenditure (r = 0.586, p < 0.001). The annual financial resources per inhabitant were also subject to fluctuations ranging from 9476 $ (Switzerland) to 140 $ (Ukraine); however, there were countries with high financial means, such as Switzerland or Scandinavian countries, which showed significantly lower implantation rates. CONCLUSION: There were considerable differences in CIED implantations in Europe. These seem to be explained in part by socioeconomic disparities within Europe. Also, a potential influence by the respective remuneration system is likely.

Cardiovascular Biomarkers for Prediction of in-hospital and 1-Year Post-discharge Mortality in Patients With COVID-19 Pneumonia.

Aims: While COVID-19 affects the cardiovascular system, the potential clinical impact of cardiovascular biomarkers on predicting outcomes in COVID-19 patients is still unknown. Therefore, to investigate this issue we analyzed the prognostic potential of cardiac biomarkers on in-hospital and long-term post-discharge mortality of patients with COVID-19 pneumonia. Methods: Serum soluble ST2, VCAM-1, and hs-TnI were evaluated upon admission in 280 consecutive patients hospitalized with COVID-19-associated pneumonia in a single, tertiary care center. Patient clinical and laboratory characteristics and the concentration of biomarkers were correlated with in-hospital [Hospital stay: 11 days (10; 14)] and post-discharge all-cause mortality at 1 year follow-up [FU: 354 days (342; 361)]. Results: 11 patients died while hospitalized for COVID-19 (3.9%), and 11 patients died during the 1-year post-discharge follow-up period (n = 11, 4.1%). Using multivariate analysis, VCAM-1 was shown to predict mortality during the hospital period (HR 1.081, CI 95% 1.035;1.129, p = 0.017), but not ST2 or hs-TnI. In contrast, during one-year FU post hospital discharge, ST2 (HR 1.006, 95% CI 1.002;1.009, p < 0.001) and hs-TnI (HR 1.362, 95% CI 1.050;1.766, p = 0.024) predicted mortality, although not VCAM-1. Conclusion: In patients hospitalized with Covid-19 pneumonia, elevated levels of VCAM-1 at admission were associated with in-hospital mortality, while ST2 and hs-TnI might predict post-discharge mortality in long term follow-up.

Main pulmonary artery diameter in combination with cardiovascular biomarkers. New possibilities to identify pulmonary hypertension in patients with severe aortic valve stenosis?

BACKGROUND: Echocardiography is currently the noninvasive method of choice to screen patients with severe aortic valve stenosis (AS) for pulmonary hypertension (PH) by estimating systolic pulmonary artery pressure (sPAP). However, radiological options are also available by determining the main pulmonary artery (MPA) diameter in the setting of CT angiography. The aim of the present study was to compare cardiovascular biomarkers with the MPA diameter to allow other ways of detecting PH in patients with severe AS. METHODS: 194 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR) were included in this study and were divided into two groups based on the CT-angiographically determined MPA diameter. In accordance with ESC guidelines, a cut-off value of 29 mm was determined in this study, with the absence of PH defined by an MPA diameter < 29 mm (n = 79/194) and the presence of PH defined by an MPA diameter ≥ 29 mm (115/194). Immediately before interventional aortic valve replacement, blood samples were drawn from the subjects and relevant cardiovascular biomarkers such as BNP, cTnI, GDF-15, H-FABP, IGF-BP2 and suPAR were assessed. RESULTS: Patients with an MPA diameter ≥ 29 mm had significantly higher BNP (p = 0.004), cTnI (p = 0.039) and HFABP (p = 0.015) plasma levels, whereas GDF-15 (p = 0.140), IGF-BP2 ( p = 0.088) and suPAR (p = 0.140) showed no significant differences. In addition, cut-off values were calculated to predict an MPA diameter ≥ 29 mm. Significant results were shown with 1634.00 pg/ml for BNP (p = 0.004), with 16.50 pg/ml for cTnI (p = 0.039) and with 1.16 ng/ml for H-FABP (p = 0.016). In a combined biomarker analysis, the 2-way combination of BNP and IGF-BP2 (AUC 0.671; 95%CI 0.538 - 0.805; p = 0.023) and the 3-way combination of BNP, H-FABP and IGF-BP2 (AUC 0.685; 95%CI 0.551 - 0.818; p = 0.015) showed the best results. Biomarker follow-up at 3 and 12 months after TAVR did not require additional information gain. Regarding 1-year survival, no significant difference could be detected between patients with an MPA diameter < 29 mm compared to patients with ≥ 29 mm (log-rank test: p = 0.262). CONCLUSIONS: The MPA diameter remains a controversial parameter for the detection of PH in patients with severe AS. Standing on its own, this non-invasive parameter may not be precise enough to detect PH accurately. Combining this parameter with several biomarkers did not provide significant additional information.

Differences of Hemogram Parameters and Their Ratios among Patients with Takotsubo Syndrome, Acute Coronary Syndrome and Healthy Individuals.

Introduction: Takotsubo cardiomyopathy (TTC) and acute coronary syndrome (ACS) are clinically indistinguishable from each other. Although therapeutically redundant, coronary angiography remains indispensable for differential diagnosis. Methods: In our study, we compared hemogram parameters and their ratios in 103 patients presenting with undiagnosed chest pain. Blood was drawn at baseline in 40 patients with TTC, 63 patients with ACS, and 68 healthy controls ((Ctrl) no coronary artery disease or signs of heart failure). Results: Peripheral lymphocyte counts were significantly depressed in TTC and ACS patients when compared to the Ctrl. Consequently, all three investigated hemogram ratios were significantly elevated in patients with ACS or TTC (NLR: TTC: median 3.20 vs. ACS: median 3.82 vs. Ctrl: median 2.10, p < 0.0001; BLR: median 0.02 vs. ACS: median 0.00 vs. Ctrl: median 0.00, p < 0.0001; MLR: median 0.37 vs. ACS: median 0.44 vs. Ctrl: median 0.28, p < 0.0001). Of note, BLR was only significantly elevated in patients with TTC, and not in patients with ACS (ACS vs. Ctrl p = 0.183). Conclusion: Basophil count and BLR are significantly increased in TTC patients when compared to ACS and may, therefore, be helpful in the distinction of TTC from ACS. Whereas NLR might be useful to differentiate ACS from controls. Elevated basophil counts and BLR in TTC patients are interesting findings and may confirm speculations about the partly unexplained pathophysiology.

Gender-Specific Differences in the Intensive Care Treatment of COVID-19 Patients.

BACKGROUND: Gender-specific differences in the outcome of COVID-19 patients requiring intensive care treatment have been reported. However, a potential association with ICU therapy remains elusive. METHODS: A total of 224 consecutive patients (63 women) treated for severe COVID-19 disease requiring mechanical ventilation were screened for the study. After propensity score matching for gender, 40 men and 40 women were included in the study. Comparative analysis was conducted for laboratory parameters, ICU therapy and complications (pulmonary embolism, thrombosis, stroke, and ventricular arrhythmias), and outcome (mortality). RESULTS: Male patients had significantly higher levels of CRP (p = 0.012), interleukin-6 (p = 0.020) and creatinine (p = 0.027), while pH levels (p = 0.014) were significantly lower compared to females. Male patients had longer intubation times (p = 0.017), longer ICU stays (p = 0.022) and higher rates of catecholamine dependence (p = 0.037). Outcome, complications and ICU therapy did not differ significantly between both groups. CONCLUSION: The present study represents the first matched comparison of male and female COVID-19 patients requiring intensive care treatment. After propensity matching, male patients still displayed a higher disease severity. This was reflected in higher rates of vasopressors, duration of ICU stay and duration of intubation. In contrast, no significant differences were observed in mortality rates, organ replacement therapy and complications during ICU stay.

Pretreatment with Betablockers, a Potential Predictor of Adverse Cardiovascular Events in Takotsubo Syndrome.

Introduction: Treatment with betablockers is controversial in Takotsubo syndrome (TTS); however, many physicians intuitively initiate or continue betablocker therapy in these patients. The effect of preadmission betablocker use on adverse cardiovascular events has not been studied in the literature. Methods: To investigate this issue, we evaluated clinical complications, defined by the endpoint of occurrence of hemodynamically relevant arrythmia, cardiac decompensation, and all-cause adverse cardiac events, during hospitalization, in 56 patients hospitalized for TTS between April 2017 and July 2021. We compared the risk of adverse cardiovascular events between patients with preadmission betablocker therapy and those without preadmission betablocker therapy. Pretreatment betablocker therapy was defined as daily betablocker intake for more than a week including day of admission. Results: TTS patients taking preadmission betablockers had a significantly increased risk of all-cause complications relative to patients without betablockers in preadmission medication ((52.0% vs. 19.4%, p = 0.010; OR 4.5 (95% Cl 1.38-14.80)). Furthermore, TTS patients already taking betablockers on admission showed a statistically significant increased risk of cardiac decompensation when compared to patients without pretreatment with betablockers (p = 0.013). There were no significant differences in patient characteristics in patients who were taking beta blockers as an adjunct therapy prior to admission for TTS relative to those who were not. There is however an increase in comorbidities, hypertension, and atrial fibrillation, in past medical history in patients taking a preadmission betablocker. The difference is related to therapeutic applications for beta blockers and was not significant based on endpoints of our study. Conclusions: Preadmission betablocker treatment was associated with a 4.5 times higher risk of adverse cardiac events. This increased risk of all-cause complications and of cardiac decompensation within the acute phase of TTS is presumably due to the negative inotropic effects of betablockers and upregulation of ß-adrenergic receptors in patients with chronic betablocker therapy.

How spaceflight challenges human cardiovascular health.

The harsh environmental conditions in space, particularly weightlessness and radiation exposure, can negatively affect cardiovascular function and structure. In the future, preventive cardiology will be crucial in enabling safe space travel. Indeed, future space missions destined to the Moon and from there to Mars will create new challenges to cardiovascular health while limiting medical management. Moreover, commercial spaceflight evolves rapidly such that older persons with cardiovascular risk factors will be exposed to space conditions. This review provides an overview on studies conducted in space and terrestrial models, particularly head-down bedrest studies. These studies showed that weightlessness elicits a fluid shift towards the head, which likely predisposes to the spaceflight-associated neuro-ocular syndrome, neck vein thrombosis, and orthostatic intolerance after return to Earth. Moreover, cardiovascular unloading produces cardiopulmonary deconditioning, which may be associated with cardiac atrophy. In addition to limiting physical performance, the mechanism further worsens orthostatic tolerance after return to Earth. Finally, space conditions may directly affect vascular health; however, the clinical relevance of these findings in terms of morbidity and mortality is unknown. Targeted preventive measures, which are referred to as countermeasures in aerospace medicine, and technologies to identify vascular risks early on will be required to maintain cardiovascular performance and health during future space missions.

Dexamethasone Improves Cardiovascular Outcomes in Critically Ill COVID-19, a Real World Scenario Multicenter Analysis.

BACKGROUND: Severe COVID-19 pneumonia requiring intensive care treatment remains a clinical challenge to date. Dexamethasone was reported as a promising treatment option, leading to a reduction of mortality rates in severe COVID-19 disease. However, the effect of dexamethasone treatment on cardiac injury and pulmonary embolism remains largely elusive. METHODS: In total 178 critically ill COVID-19 patients requiring intensive care treatment and mechanical ventilation were recruited in three European medical centres and included in the present retrospective study. One hundred thirteen patients (63.5%) were treated with dexamethasone for a median duration of 10 days (IQR 9-10). Sixty five patients (36.5%) constituted the non-dexamethasone control group. RESULTS: While peak inflammatory markers were reduced by dexamethasone treatment, the therapy also led to a significant reduction in peak troponin levels (231 vs. 700% indicated as relative to cut off value, p = 0.001). Similar, dexamethasone resulted in significantly decreased peak D-Dimer levels (2.16 mg/l vs. 6.14 mg/l, p = 0.002) reflected by a significant reduction in pulmonary embolism rate (4.4 vs. 20.0%, p = 0.001). The antithrombotic effect of dexamethasone treatment was also evident in the presence of therapeutic anticoagulation (pulmonary embolism rate: 6 vs. 34.4%, p < 0.001). Of note, no significant changes in baseline characteristics were observed between the dexamethasone and non-dexamethasone group. CONCLUSION: In severe COVID-19, anti-inflammatory effects of dexamethasone treatment seem to be associated with a significant reduction in myocardial injury. Similar, a significant decrease in pulmonary embolism, independent of anticoagulation, was evident, emphasizing the beneficial effect of dexamethasone treatment in severe COVID-19.

Higher Incidence of Stroke in Severe COVID-19 Is Not Associated With a Higher Burden of Arrhythmias: Comparison With Other Types of Severe Pneumonia.

Aims: Thromboembolic events, including stroke, are typical complications of COVID-19. Whether arrhythmias, frequently described in severe COVID-19, are disease-specific and thus promote strokes is unclear. We investigated the occurrence of arrhythmias and stroke during rhythm monitoring in critically ill patients with COVID-19, compared with severe pneumonia of other origins. Methods and Results: This retrospective study included 120 critically ill patients requiring mechanical ventilation in three European tertiary hospitals, including n =60 COVID-19, matched according to risk factors for the occurrence of arrhythmias in n = 60 patients from a retrospective consecutive cohort of severe pneumonia of other origins. Arrhythmias, mainly atrial fibrillation (AF), were frequent in COVID-19. However, when compared with non-COVID-19, no difference was observed with respect to ventricular tachycardias (VT) and relevant bradyarrhythmias (VT 10.0 vs. 8.4 %, p = ns and asystole 5.0 vs. 3.3%, p = ns) with consequent similar rates of cardiopulmonary resuscitation (6.7 vs. 10.0%, p = ns). AF was even more common in non-COVID-19 (AF 18.3 vs. 43.3%, p = 0.003; newly onset AF 10.0 vs. 30.0%, p = 0.006), which resulted in a higher need for electrical cardioversion (6.7 vs. 20.0%, p = 0.029). Despite these findings and comparable rates of therapeutic anticoagulation (TAC), the incidence of stroke was higher in COVID-19 (6.7.% vs. 0.0, p = 0.042). These events also happened in the absence of AF (50%) and with TAC (50%). Conclusions: Arrhythmias were common in severe COVID-19, consisting mainly of AF, yet less frequent than in matched pneumonia of other origins. A contrasting higher incidence of stroke independent of arrhythmias also observed with TAC, seems to be an arrhythmia-unrelated disease-specific feature of COVID-19.

J-waves in acute COVID-19: A novel disease characteristic and predictor of mortality?

BACKGROUND: J-waves represent a common finding in routine ECGs (5-6%) and are closely linked to ventricular tachycardias. While arrhythmias and non-specific ECG alterations are a frequent finding in COVID-19, an analysis of J-wave incidence in acute COVID-19 is lacking. METHODS: A total of 386 patients consecutively, hospitalized due to acute COVID-19 pneumonia were included in this retrospective analysis. Admission ECGs were analyzed, screened for J-waves and correlated to clinical characteristics and 28-day mortality. RESULTS: J-waves were present in 12.2% of patients. Factors associated with the presence of J-waves were old age, female sex, a history of stroke and/or heart failure, high CRP levels as well as a high BMI. Mortality rates were significantly higher in patients with J-waves in the admission ECG compared to the non-J-wave cohort (J-wave: 14.9% vs. non-J-wave 3.8%, p = 0.001). After adjusting for confounders using a multivariable cox regression model, the incidence of J-waves was an independent predictor of mortality at 28-days (OR 2.76 95% CI: 1.15-6.63; p = 0.023). J-waves disappeared or declined in 36.4% of COVID-19 survivors with available ECGs for 6-8 months follow-up. CONCLUSION: J-waves are frequently and often transiently found in the admission ECG of patients hospitalized with acute COVID-19. Furthermore, they seem to be an independent predictor of 28-day mortality.

Tumor necrosis factor alpha-an underestimated risk predictor in patients undergoing transcatheter aortic valve replacement (TAVR)?

BACKGROUND: Systemic inflammation has been identified as a major cardiovascular risk factor in patients undergoing transcatheter aortic valve replacement (TAVR), yet currently, it is not adequately portrayed in scores for pre-interventional risk assessment. The aim of this study was to investigate the predictive ability of TNF-α in TAVR. METHODS: A total of 431 patients undergoing transfemoral TAVR were enrolled in this study. Blood samples were drawn prior to intervention, 24 h post-intervention, 4, 5, and 7 days post-intervention, and 1, 3, and 6 months post-TAVR. RESULTS: In a univariate Cox proportional hazard analysis, plasma concentrations of TNF-α after 24 h and after 5 days were associated with mortality after 12 months (after 24 h: HR 1.002 (1.000-1.004), p = 0.028; after 5d: HR 1.003 (1.001-1.005), p = 0.013). This association remained significant even after correction for confounders in a multivariate Cox regression analysis. Additionally, cut-offs were calculated. Patients above the cut-off for TNF-α after 5d had a significantly worse 12-month mortality than patients below the cut-off (18.8% vs. 2.8%, p = 0.046). CONCLUSION: Plasma levels of TNF-α after 24 h and 5 days were independently associated with 12-month mortality in patients undergoing TAVR. Thus, TNF-α could represent a novel biomarker for enhanced risk stratification in these patients.

Thinking fast and slow: lactate and MELD-XI (model for end-stage liver disease excluding INR) are useful for estimating mortality after cardiopulmonary resuscitation.

BACKGROUND: Intensivists keep getting challenged with prognostication after cardiopulmonary resuscitation (CPR). The model for end-stage liver disease, excluding INR (MELD-XI) Score has proven valuable for assessing illness severity. Serum lactate is a readily available and established indicator of general stress and tissue hypoxia. We aimed to evaluate the prognostic value of MELD-XI combined with serum lactate in patients after CPR. METHODS: A retrospective analysis on 106 patients after CPR was performed. Multivariable Cox regression was performed to evaluate associations with 30-day mortality and neurological outcome by means of cerebral performance category (CPC). An optimal cut-off was calculated by means of the Youden Index. Patients were then divided into subgroups based on the optimal cut-offs for MELD-XI and serum lactate. RESULTS: MELD-XI and lactate were independently associated with mortality. The respective cut-offs were MELD-XI>12 and lactate ≥2.5 mmol/L. Patients were split into three groups: lactate <2.5 mmol/L and MELD-XI≤12 (low-risk; N.=32), lactate ≥2.5 mmol/L or MELD-XI>12 (medium-risk; N.=39), and lactate ≥2.5 mmol/L and MELD-XI >12 (high-risk; N.=33). The mortality rates were 6%, 26% and 61% in the low, medium and high-risk group. This combined model yielded in the highest predictive abilities (AUC=0.78 95%CI: 0.68-0.85; P=0.03 vs. AUC=0.66 for SOFA Score). Worse neurological outcome (CPC 3 or 4) was more common in the medium and high-risk group (6.25%, 10.3% and 9.1%). CONCLUSIONS: The combination of MELD-XI and lactate concentration at ICU admission was superior to the more complex SOFA Score for prediction of mortality after CPR.