Environmental factors and their impact on the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in numerous cases of illness and death worldwide. Research has shown that there are associations between transmission, as well as the severity of SARS-CoV­2 (severe acute respiratory syndrome coronavirus 2) infections, and various environmental factors. For example, air pollution with particulate matter is thought to play a crucial role, and both climatic and geographical aspects must be considered. Furthermore, environmental conditions such as industry and urban lifestyle have a significant impact on air quality and thus on health aspects of the population. In this regard, other factors such as chemicals, microplastics, and diet also critically impact health, including respiratory and cardiovascular diseases. Overall, the COVID-19 pandemic has highlighted how closely health and the environment are linked. This review discusses the impact of environmental factors on the COVID-19 pandemic.

A practical approach for the treatment of post-COVID symptoms.

For the past 3 years, our daily lives have been largely dictated by the coronavirus disease 2019 (COVID-19) pandemic. In many people, this infectious disease leads to long-lasting symptoms, which can vary greatly in form and intensity between individuals. This report describes the case of a young patient who had no health restrictions until she came into contact with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As part of a post-COVID syndrome, she not only temporarily lost her ability to work, but was also no longer able to manage her daily life independently. A crucial therapeutic approach, in this case, was the use of heparin-induced extracorporeal LDL/fibrinogen precipitation (H.E.L.P.) apheresis.

Management of a severe abdominal compartment complicating fulminant cardiogenic-septic shock: An abdominal arterio-venous single-tube ECMO bypass saved a young patient's life after OHCA.

INTRODUCTION: In severe cardiogenic shock, for example, following cardiac arrest, the implantation of an extracorporeal hemodynamic assist device often seems to be the last option to save a patient's life. However, even though our guidelines provide a class-IIa-recommendation to implant a veno-arterial extracorporeal membrane oxygenation (vaECMO) device in these patients, the accompanying disease- and device-associated complications and their consequences remain challenging to handle. CASE PRESENTATION: A 43-year-old patient presented with severe cardiogenic-septic shock with a complicating abdominal compartment due to a prolonged out-of-hospital cardiac arrest (OHCA). A loss of function of the vaECMO, implanted immediately after admission, impended due to increasing intra-abdominal pressure. This dangerous situation was resolved by crafting an experimental "arterio-venous shunt," using the side port of the reinfusion (arterial) vaECMO cannula and a downstream large-volume central access in the right femoral vein toward the abdominal venous system, which led to the patient's full recovery. CONCLUSION: In patients with cardiogenic shock, the use of catecholamines and implantation of extracorporeal assist devices alone do not ensure successful therapy. To optimize the outcome, device- and disease-associated complications must also be managed in a timely and minimally invasive procedure.

[Acute Coronary Syndrome (ACS) in Preclinical Emergency Medicine]. / Das akute Koronarsyndrom in der präklinischen Notfallmedizin.

Acute coronary syndrome (ACS) is a common diagnosis in preclinical emergency medicine. The term summarizes the acute manifestations of coronary artery disease. It ranges from unstable angina pectoris via cardiogenic shock to sudden cardiac death. The leading key symptom is chest pain. With this trigger symptom, a clinical diagnostic algorithm is initiated, acting quickly on the suspected diagnosis of acute myocardial infarction. Due to the potentially life-threatening course, rapid diagnosis and initiation of therapeutic measures is crucial. Pre-clinical antithrombotic medication and therapy for accompanying symptoms are paramount. As part of the initial assessment, important differential diagnoses should be considered and, within the first 10 minutes after medical contact, an ECG diagnosis should differentiate between ACS with and without ST segment elevations. If ACS is diagnosed, acetylsalicylic acid should be given to inhibit platelet aggregation. The benefits outweigh the very low risk of unnecessary administration. Patients with ACS should be taken to hospital immediately for coronary interventions (PCI). In the case of an ACS with ST segment elevations, reperfusion therapy should be carried out within 120 minutes. In the case of an ACS without ST segment elevations, the time limit (2 - 72 h) until reperfusion is based on the risk stratification. In the majority of cases, the coronary stenosis causing the infarction can be treated with PCI. However, invasive diagnostics show no significant stenosis in a significant proportion of patients with myocardial infarction (prevalence 1 - 14%). This is known as "myocardial infarction with non-obstructive coronary arteries" (MINOCA) and further differential diagnosis should be initiated in these patients.

Structural, Pro-Inflammatory and Calcium Handling Remodeling Underlies Spontaneous Onset of Paroxysmal Atrial Fibrillation in JDP2-Overexpressing Mice.

BACKGROUND: Cardiac-specific JDP2 overexpression provokes ventricular dysfunction and atrial dilatation in mice. We performed in vivo studies on JDP2-overexpressing mice to investigate the impact of JDP2 on the predisposition to spontaneous atrial fibrillation (AF). METHODS: JDP2-overexpression was started by withdrawal of a doxycycline diet in 4-week-old mice. The spontaneous onset of AF was documented by ECG within 4 to 5 weeks of JDP2 overexpression. Gene expression was analyzed by real-time RT-PCR and Western blots. RESULTS: In atrial tissue of JDP2 mice, besides the 3.6-fold increase of JDP2 mRNA, no changes could be detected within one week of JDP2 overexpression. Atrial dilatation and hypertrophy, combined with elongated cardiomyocytes and fibrosis, became evident after 5 weeks of JDP2 overexpression. Electrocardiogram (ECG) recordings revealed prolonged PQ-intervals and broadened P-waves and QRS-complexes, as well as AV-blocks and paroxysmal AF. Furthermore, reductions were found in the atrial mRNA and protein level of the calcium-handling proteins NCX, Cav1.2 and RyR2, as well as of connexin40 mRNA. mRNA of the hypertrophic marker gene ANP, pro-inflammatory MCP1, as well as markers of immune cell infiltration (CD68, CD20) were increased in JDP2 mice. CONCLUSION: JDP2 is an important regulator of atrial calcium and immune homeostasis and is involved in the development of atrial conduction defects and arrhythmogenic substrates preceding paroxysmal AF.

Suppressor of Cytokine Signaling 1 is Involved in Gene Regulation Which Controls the Survival of Ly6Clow Monocytes in Mice.

BACKGROUND/AIMS: Inflammatory processes are controlled by the fine-tuned balance of monocyte subsets. In mice, different subsets of monocytes can be distinguished by the expression of Ly6C that is highly expressed on inflammatory monocytes (Ly6Chigh) and to a lesser extent on patrolling monocytes (Ly6Clow). Our previous study revealed an accumulation of Ly6Chigh monocytes in atherosclerotic-prone mice bearing a deficiency in suppressor of cytokine signaling (SOCS)-1 leading to an increased atherosclerotic burden. To decipher the underlying mechanisms, we performed a genome-wide analysis of SOCS-1-dependent gene regulation in Ly6Chigh and Ly6Clow monocytes. METHODS: In monocyte subsets from SOCS-1competent and -deficient mice differentially regulated genes were identified using an Illumina mRNA microarray (45,200 transcripts), which were randomly validated by qPCR. Principal component analysis was performed to further characterize mRNA profiles in monocyte subsets. To unravel potential regulatory mechanisms behind the differential mRNA expression, in silico analysis of a transcription factor (TF) network correlating with SOCS-1-dependent mRNA expression was carried out and combined with a weighted correlation network analysis (WGCNA). RESULTS: mRNA analysis in monocyte subsets revealed 46 differentially regulated genes by 2-fold or more. Principal component analysis illustrated a distinct separation of mRNA profiles in monocyte subsets from SOCS-1-deficient mice. Notably, two cell surface receptors crucially involved in the determination of monocyte differentiation and survival, C-X3-C chemokine receptor 1 (CX3CR1) and colony stimulating factor 1 receptor (CSF1R), were identified to be regulated by SOCS-1. Moreover, in silico analysis of a TF network in combination with the WGCNA revealed genes coding for PPAR-γ, NUR77 and several ETSdomain proteins that act as pivotal inflammatory regulators. CONCLUSION: Our study reveals that SOCS-1 is implicated in a TF network regulating the expression of central transcription factors like PPAR-γ and NUR77 thereby influencing the expression of CX3CR1 and CSF1R that are known to be pivotal for the survival of Ly6Clow monocytes.

Prognosis of pacing-dependent patients with cardiovascular implantable electronic devices.

BACKGROUND: Data on the prognostic significance of pacing dependency in patients with cardiovascular implantable electronic devices (CIEDs) are sparse. METHODS: The prognostic significance of pacing dependency defined as absence of an intrinsic rhythm ≥ 30 bpm was determined in 786 patients with CIEDs at the authors' institution using univariate and multivariate regression analysis to identify predictors of all-cause mortality. RESULTS: During 49 months median follow-up, death occurred in 63 of 130 patients with pacing dependency compared to 241 of 656 patients without pacing dependency (48% versus 37%, hazard ratio [HR] 1.34; 95% confidence interval [CI]: 1.02-1.78, P = 0.04). Using multivariate regression analysis, predictors of all-cause mortality included age (HR 1.07; 95% CI: 1.05-1.08, P < 0.01), history of atrial fibrillation (HR 1.32, 95% CI: 1.03-1.69, P < 0.01), chronic kidney disease (HR 1.28; 95% CI: 1.00-1.63, P = 0.048) and New York Heart Association (NYHA) class ≥ III (HR 2.00; 95% CI: 1.52-2.62, P < 0.01), but not pacing dependency (HR 1.15; 95% CI: 0.86-1.54, P = 0.35). CONCLUSIONS: In contrast to age, atrial fibrillation, chronic kidney disease and heart failure severity as indexed by NYHA functional class III or IV, pacing dependency does not appear to be an independent predictor of all-cause mortality in patients with CIEDs.

Monitoring a Mystery: The Unknown Right Ventricle during Left Ventricular Unloading with Impella in Patients with Cardiogenic Shock.

Background: Right ventricular (RV) dysfunction or failure occurs in more than 30% of patients in cardiogenic shock (CS). However, the importance of timely diagnosis of prognostically relevant impairment of RV function is often underestimated. Moreover, data regarding the impact of mechanical circulatory support like the Impella on RV function are rare. Here, we investigated the effects of the left ventricular (LV) Impella on RV function. Moreover, we aimed to identify the most optimal and the earliest applicable parameter for bedside monitoring of RV function by comparing the predictive abilities of three common RV function parameters: the pulmonary artery pulsatility index (PAPi), the ratio of right atrial pressure to pulmonary capillary wedge pressure (RA/PCWP), and the right ventricular stroke work index (RVSWI). Methods: The data of 50 patients with CS complicating myocardial infarction, supported with different flow levels of LV Impella, were retrospectively analyzed. Results: Enhancing Impella flow (1.5 to 2.5 L/min ± 0.4 L/min) did not lead to a significant variation in PAPi (p = 0.717), RA/PCWP (p = 0.601), or RVSWI (p = 0.608), indicating no additional burden for the RV. PAPi revealed the best ability to connect RV function with global hemodynamic parameters, i.e., cardiac index (CI; p < 0.001, 95% CI: 0.181-0.663), pulmonary capillary wedge pressure (PCWP; p = 0.005, 95% CI: -6.721--1.26), central venous pressure (CVP; p < 0.001, 95% CI: -7.89-5.575), and indicators of tissue perfusion (central venous oxygen saturation (SvO2); p = 0.008, 95% CI: 1.096-7.196). Conclusions: LV Impella does not impair RV function. Moreover, PAPi seems to be to the most effective and valid predictor for early bedside monitoring of RV function.

Early goal-directed management after out-of-hospital cardiac arrest: lessons from a certified cardiac Arrest centre.

BACKGROUND: Despite continuous advances in post-resuscitation management, outcome after out-of-hospital cardiac arrest (OHCA) is limited. To improve the outcome, interdisciplinary Cardiac Arrest Centers (CACs) have been established in recent years, but survival remains low and treatment strategies vary considerably in clinical and geographical aspects. Here we analyzed a strategy of in-hospital post-resuscitation management while evaluating the outcome. METHODS: A broad spectrum of pre- and in-hospital parameters of 545 resuscitated patients, admitted to the Cardiac Arrest Center of the University Hospital of Marburg (MCAC) between 01/2018 and 12/2022 were retrospectively analyzed. Inclusion criteria were ≥ 18 years, resuscitation by emergency medical services, and non-traumatic cause of OHCA. RESULTS: In the overall patient cohort, the survival rate to hospital discharge was 39.8% (n = 217/545), which is 50.7% higher than in the EuReCa-TWO registry. 77.2% of the survivors had CPC status 1 or 2 (favorable neurological outcome) before and after therapy. A standardized 'therapy bundle' for in-hospital post-resuscitation management was applied to 445 patients who survived the initial treatment in the emergency department. In addition to basic care (standardized antimicrobial therapy, adequate anticoagulation, targeted sedation, early enteral and parenteral nutrition), it includes early whole-body CT (n = 391; 87.9%), invasive coronary diagnostics (n = 322; 72.4%), targeted temperature management (n = 293; 65.8%) and if indicated, mechanical circulatory support (n = 145; 32.6%) and appropriate neurological diagnostics. CONCLUSIONS: Early goal-directed post-resuscitation management in a well-established and highly frequented CAC leads to significantly higher survival rates. However, our results underline the need for a broader standardization in post-resuscitation management to ultimately improve the outcome.

Discussion of hemodynamic optimization strategies and the canonical understanding of hemodynamics during biventricular mechanical support in cardiogenic shock: does the flow balance make the difference?

BACKGROUND: Mechanical circulatory support (MCS) devices may stabilize patients with severe cardiogenic shock (CS) following myocardial infarction (MI). However, the canonical understanding of hemodynamics related to the determination of the native cardiac output (CO) does not explain or support the understanding of combined left and right MCS. To ensure the most optimal therapy control, the current principles of hemodynamic measurements during biventricular support should be re-evaluated. METHODS: Here we report a protocol of hemodynamic optimization strategy during biventricular MCS (VA-ECMO and left ventricular Impella) in a case series of 10 consecutive patients with severe cardiogenic shock complicating myocardial infarction. During the protocol, the flow rates of both devices were switched in opposing directions (+ / - 0.7 l/min) for specified times. To address the limitations of existing hemodynamic measurement strategies during biventricular support, different measurement techniques (thermodilution, Fick principle, mixed venous oxygen saturation) were performed by pulmonary artery catheterization. Additionally, Doppler ultrasound was performed to determine the renal resistive index (RRI) as an indicator of renal perfusion. RESULTS: The comparison between condition 1 (ECMO flow > Impella flow) and condition 2 (Impella flow > VA-ECMO flow) revealed significant changes in hemodynamics. In detail, compared to condition 1, condition 2 results in a significant increase in cardiac output (3.86 ± 1.11 vs. 5.44 ± 1.13 l/min, p = 0.005) and cardiac index (2.04 ± 0.64 vs. 2.85 ± 0.69, p = 0.013), and mixed venous oxygen saturation (56.44 ± 6.97% vs. 62.02 ± 5.64% p = 0.049), whereas systemic vascular resistance decreased from 1618 ± 337 to 1086 ± 306 s*cm-5 (p = 0.002). Similarly, RRI decreased in condition 2 (0.662 ± 0.05 vs. 0.578 ± 0.06, p = 0.003). CONCLUSIONS: To monitor and optimize MCS in CS, PA catheterization for hemodynamic measurement is applicable. Higher Impella flow is superior to higher VA-ECMO flow resulting in a more profound increase in CO with subsequent improvement of organ perfusion.

Hemoadsorption as part of a multimodal therapy concept to treat Capnocytophaga sepsis with thrombocytopenia and multiple organ failure.

BACKGROUND: Capnocytophaga, a bacteria native to the oral flora of canines, in rare cases can lead to severe infections resulting in septic shock, respiratory tract infection, and multiple organ failure. In case of trauma following animal bites with rapidly progressing clinical courses, also adjunctive therapeutic measures such as extracorporeal blood purification therapies might be beneficial. CASE PRESENTATION: We report on a 68-year-old male who was hospitalized with fever, oliguria and repeated vomiting after suffering a minor bite by his dog. On admission, he was diagnosed with sepsis. In addition, his coagulation status was markedly deranged resulting in the administration of mass transfusions to stabilize his coagulative status. Following detection of Capnocytophaga canimorsus, anti-infective therapy was initiated. In the context of a progressive respiratory deterioration and an increasing vigilance disorder, he had to be intubated. Due to development of renal failure, dialysis was started in conjunction with CytoSorb hemoadsorption therapy to control the hyperinflammatory condition. All of the applied therapeutic measures led to a rapid clinical stabilization, a control of the hyperinflammatory situation, and an improvement in his neurological status. The therapy was well tolerated with no complications encountered. CONCLUSIONS: This case supports the clinical recognition of severe Capnocytophaga infection that can lead to critical conditions even in immunocompetent patients. Combined broad spectrum antibiotic therapy, mass transfusions, CRRT, and CytoSorb hemoadsorption therapy resulted in a control of the critical situation. However, further research is needed to fully elucidate the role of hemoadsorption in this rare but life-threatening setting.

The Impact of Positive Inotropic Therapy on Hemodynamics and Organ Function in Acute Heart Failure: A Differentiated View.

BACKGROUND: Little is known about the impact of treatment with inotropic drugs on the interaction of hemodynamics, biomarkers, and end-organ function in patients with acute decompensated heart failure (HF) of different origins and heart rhythms. METHODS: Fifty patients with different causes of acute decompensated HF (dilated cardiomyopathy DCM, ischemic cardiomyopathy ICM, atrial fibrillation AF, sinus rhythm/pacemaker lead rhythm SR/PM) were treated with dobutamine or levosimendan. Non-invasive hemodynamics, biomarkers, and parameters of renal organ function were evaluated at hospital admission and after myocardial recompensation (day 5 to 7). RESULTS: Twenty-seven patients with ICM and twenty-three patients with DCM were included. Thirty-nine patients were treated with dobutamine and eleven with levosimendan. Sixteen were accompanied by persistent AF and thirty-four presented either with SR or PM. In the overall cohort, body weight and biomarkers (NT-proBNP/ST2) significantly decreased. GFR significantly increased during therapy with either dobutamine or levosimendan. However, hemodynamic parameters seem to be only improved in patients with DCM, in the levosimendan sub-group, and in patients with SR/PM. CONCLUSION: Patients with acute decompensated HF benefit from positive inotropic therapy during short-term follow-ups. In particular, patients with DCM, those after levosimendan therapy and those with SR/PM, seem to benefit most from inotropic therapy.

New-Onset Atrial Fibrillation in the Setting of COVID-19 Infection Is a Predictor of Mortality in Hospitalized Patients: CovAF-Study.

Recent studies show that hospitalized COVID-19 patients have an increased incidence of arrhythmia, especially atrial fibrillation (AF). This single-center study included 383 hospitalized patients with positive polymerase chain reaction tests for COVID-19 from March 2020 to April 2021. Patient characteristics were documented, and data were analyzed for episodes of AF on admission or during the hospital stay, intrahospital mortality, need for intensive care and/or invasive ventilation, inflammatory parameters (hs-CRP, IL-6, and procalcitonin), and differential blood count. We demonstrated that in the setting of hospitalized cases of COVID-19 infection, there is an incidence of 9.8% (n = 36) for the occurrence of new-onset AF. Furthermore, it was shown that a total of 21% (n = 77) had a history of episodes of paroxysmal/persistent AF. However, only about one-third of patients with pre-existing AF had relevant documented tachycardic episodes during the hospital stay. Patients with new-onset AF had a significantly increased intrahospital mortality compared to the control and the pre-existing AF without rapid ventricular rate (RVR) group. Patients with new-onset AF required intensive care and invasive ventilation more frequently. Further analysis examined patients with episodes of RVR and demonstrated that they had significantly elevated CRP (p < 0.05) and PCT (p < 0.05) levels on the day of hospital admission compared to patients without RVR.

Chronological Development of Cardiovascular Disease in Times of COVID-19: A Retrospective Analysis of Hospitalized Diseases of the Circulatory System and COVID-19 Patients of a German University Hospital.

This study aims at examining the chronological development of hospitalized cardiovascular and COVID-19 patients and comparing the effects on related sub-disciplines and main diagnoses for pre-pandemic (2017-2019) and pandemic (2020-2021) years in the setting of a German university maximum care provider. Data were retrospectively retrieved from the hospital performance controlling system for patient collectives with main diagnosis of diseases of the circulatory system (nCirculatory) and COVID-19 secondary diagnosis (nCOVID-19). The cardiovascular patient collective (nCirculatory = 25,157) depicts a steady state in terms of relative yearly development of patient numbers (+0.4%, 2019-2020, +0.1%, 2020-2021). Chronological assessment points towards monthly decline during lockdowns and phases of high regional incidence of COVID-19 (i.e., 2019-2020: March -10.2%, April -12.4%, December -14.8%). Main diagnoses of congestive heart failure (+16.1% 2019/2020; +19.2% 2019/2021) and acute myocardial infarction show an increase in case numbers over the course of the whole pandemic (+15.4% 2019/2020; +9.4% 2019/2021). The results confirm negative effects on the cardiovascular care situation during the entire pandemic in the setting of a university maximum care provider. A general increase in cardiac disorders and a worrisome turn in case development of acute myocardial infarction emphasize the feared cardiovascular burden of COVID-19.

Renal Protection and Hemodynamic Improvement by Impella® Microaxial Pump in Patients with Cardiogenic Shock.

Acute kidney injury is one of the most frequent and prognostically relevant complications in cardiogenic shock. The purpose of this study was to evaluate the potential effect of the Impella® pump on hemodynamics and renal organ perfusion in patients with myocardial infarction complicating cardiogenic shock. Between January 2020 and February 2022 patients with infarct-related cardiogenic shock supported with the Impella® pump were included in this single-center prospective short-term study. Changes in hemodynamics on different levels of Impella® support were documented with invasive pulmonal arterial catheter. As far as renal function is concerned, renal perfusion was assessed by determining the renal resistive index (RRI) using Doppler sonography. A total of 50 patients were included in the analysis. The increase in the Impella® output by a mean of 1.0 L/min improved the cardiac index (2.7 ± 0.86 to 3.3 ± 1.1 p < 0.001) and increased central venous oxygen saturation (62.6 ± 11.8% to 67.4 ± 10.5% p < 0.001). On the other side, the systemic vascular resistance (1035 ± 514 N·s/m5 to 902 ± 371 N·s/m5p = 0.012) and the RRI were significantly reduced (0.736 ± 0.07 to 0.62 ± 0.07 p < 0.001). Furthermore, in the overall cohort, a baseline RRI ≥ 0.8 was associated with a higher frequency of renal replacement therapy (71% vs. 39% p = 0.04), whereas the consequent reduction of the RRI below 0.7 during Impella® support improved the glomerular filtration rate (GFR) during hospital stay (15 ± 3 days; 53 ± 16 mL/min to 83 ± 16 mL/min p = 0.04). Impella® support in patients with cardiogenic shock seems to improve hemodynamics and renal organ perfusion. The RRI, a well-known parameter for the early detection of acute kidney injury, can be directly influenced by the Impella® flow rate. Thus, a targeted control of the RRI by the Impella® pump could mediate renal organ protection.

Incidence of Atrial Fibrillation in Postmenopausal Women with Endometrial Cancer.

Endometrial cancer (EC) has been associated with an increased risk of cardiovascular disease, including atrial fibrillation (AF). We performed a prospective, case-controlled analysis among 310 Bulgarian women with new-onset, histologically confirmed EC, free of AF at the baseline survey, and women with normal (senile) endometrium/endometrial hyperplasia as a control group (n = 205). The risk of AF as well as relationship of adiponectin (APN) and high sensitivity C-reactive protein (hs-CRP) levels with AF in women with EC were calculated by Cox proportional hazards models. During the mean follow-up of 2.5 ± 0.5 years, new-onset AF had occurred in 11.7% of women with EC vs. 5.8% in the control group (p < 0.01). The risk of AF was highest in the first 6 months after new-onset EC, with an incidence rate ratio (IRR) of 1.19 (95% CI 1.10-1.29; p = 0.01). Women with EC, who were obese (body mass index (BMI) > 30 kg/m2) and younger (age < 60) were found to be more likely to develop AF (HR 1.95; 95% CI 1.18-3.32; p = 0.05). APN levels were not significantly associated with new-onset AF (95% CI 0.87-1.21; p = 0.063). However, the secondary analysis showed evidence of APN-AF association when adjusted for BMI (2.05; 95% CI 1.04-4.04; p = 0.037). We conclude that EC was significantly associated with the incidence of AF.