Autoimmunity in Syndromes of Orthostatic Intolerance: An Updated Review.

Orthostatic intolerance is a broad term that represents a spectrum of dysautonomic disorders, including postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH), as manifestations of severe autonomic failure. While the etiology of orthostatic intolerance has not yet fully been uncovered, it has been associated with multiple underlying pathological processes, including peripheral neuropathy, altered renin-aldosterone levels, hypovolemia, and autoimmune processes. Studies have implicated adrenergic, cholinergic, and angiotensin II type I autoantibodies in the pathogenesis of orthostatic intolerance. Several case series have demonstrated that immunomodulation therapy resulted in favorable outcomes, improving autonomic symptoms in POTS and OH. In this review, we highlight the contemporary literature detailing the association of autoimmunity with POTS and OH.

Safety and Efficacy of Direct Oral Anticoagulant in Addition to Antiplatelet Therapy After Acute Coronary Syndrome: A Systemic Review and Meta-analysis of 53,869 Patients.

INTRODUCTION: Significant progress has been made in the management of patients with acute coronary syndrome (ACS) during the past few decades. However, the role of direct oral anticoagulants (DOACs) in post-ACS prophylactic therapy remains unknown. This study aims to assess the efficacy and safety of DOACs plus antiplatelet treatment (APT) after ACS. METHODS: A systematic literature search was conducted to identify randomized clinical trials comparing DOACs plus APT with APT alone after ACS. The primary efficacy end points were cardiovascular mortality, myocardial infarction, all-cause mortality, and stroke and systemic embolization (SSE). The primary safety end point was major bleeding. The random-effects model was used to calculate relative risk (RR) and corresponding 95% CIs. RESULTS: Nine trials with a total of 53,869 patients were identified, with 33,011 (61.2%) in the DOACs plus APT group and 20,858 (38.8%) in the APT alone group. The use of DOACs did not decrease the risk of cardiovascular death (RR = 0.87; 95% CI, 0.75-1.01; P = 0.08; I2 = 0%) or myocardial infarction (RR = 0.90; 95% CI, 0.80-1.02; P = 0.10; I2 = 6%). However, the risk of SSE was significantly lower in patients who received DOACs plus APT compared with APT alone (RR = 0.67; 95% CI, 0.50-0.90; P = 0.008). Moreover, all-cause mortality was significantly lower in the DOACs plus APT group (RR = 0.83; 95% CI, 0.71-98; P = 0.03; I2 = 0%). However, the risk of major bleeding was significantly higher in patients treated with DOACs plus APT compared with APT alone (RR = 2.53; 95% CI, 1.96-3.26; P < 0.01; I2 = 0%), as was the risk of nonmajor bleeding (RR = 2.27; 95% CI, 1.51-3.41; P < 0.01). IMPLICATIONS: DOACs plus APT for the prevention of left ventricular thrombus in patients with ACS were associated with a lower risk of SSE and all-cause mortality but increased the risk of major and nonmajor bleeding. The benefits and risks of this approach should be weighed based on a patient's individual clinical characteristics.

Monthly variations in acute coronary syndromes outcomes during the first year of the COVID-19 pandemic.

BACKGROUND: Cardiovascular disease, particularly acute coronary syndromes (ACS), is the leading cause of death in the United States. Minor fluctuations in hospital admissions for different conditions, including ACS, can be seen throughout the year. This study focuses on the impact of admission month on outcomes of acute coronary syndromes during the first year of the COVID-19 pandemic. METHODS: This was a retrospective observational study of patients hospitalized with ACS from the National Inpatient Sample, during the years 2020 (n = 779,895) and 2019 (n = 935,975). We compared the monthly outcomes for every month to the outcomes for the month of January of that same year. The primary outcomes of interest were in-hospital mortality and time from admission to PCI. RESULTS: Inpatient mortality for patients admitted with STEMI was significantly higher for admissions in the months of April, October and December of 2020 than January of that same year. For patients admitted with NSTEMI or UA, inpatient mortality was higher for admissions in April and December 2020 when compared to admissions in January 2020. Inpatient mortality for patients with STEMI, NSTEMI and UA was not different based on admission month in the year 2019. CONCLUSION: The month of admission significantly affected outcomes for patients admitted with ACS during the COVID-19 pandemic, with higher inpatient mortality and longer time from admission to PCI for certain months in 2020. Further studies should investigate disparities in monthly ACS outcomes for the year 2021 and onward, now that COVID-19 infections have been steadily declining.

Ventricular fibrillation arrest after blunt chest trauma in a 33-year-old man, commotio cordis?

BACKGROUND: Commotio cordis is an event in which a blunt, non-penetrating blow to the chest occurs, triggering a life-threatening arrhythmia and often sudden death. This phenomenon is often seen in young, male athletes and has become increasingly well-known over the past few decades. We present a unique case in which ventricular fibrillation occurs in an older male athlete after blunt trauma. CASE PRESENTATION: Patient with no known medical history was brought to the ER after being found unconscious after a soccer ball kick to the chest. He was found to be in ventricular fibrillation and successfully resuscitated on the soccer field. Patient was admitted to the hospital and lab workup and initial imaging were unremarkable, except elevated troponin and lactate, which returned to normal levels. An echocardiogram showed global left ventricular systolic dysfunction with a visually estimated ejection fraction of 45-50%. Coronary showed angiographically nonobstructive coronary arteries. The patient was diagnosed with commotio cordis and discharged from the hospital in stable condition. Follow-up echocardiogram continued to show low ejection fraction and event monitor demonstrated frequent polymorphic ventricular tachycardia with periods of asystole. CONCLUSION: This case is unique in that blunt trauma to the chest from a soccer ball immediately triggered ventricular fibrillation in a patient with a possible cardiomyopathy. It is possible that the blunt trauma caused primary commotio cordis that led to cardiomyopathy in a previous healthy man, or that an underlying cardiomyopathy made it more likely for this to occur. Overall, increased awareness and prevention efforts of blunt chest trauma are required to reduce the high mortality associated life-threatening arrhythmias. There is limited data regarding the interplay between these two entities.

E2f1-3 are critical for myeloid development.

Hematopoietic development involves the coordinated activity of differentiation and cell cycle regulators. In current models of mammalian cell cycle control, E2f activators (E2f1, E2f2, and E2f3) are portrayed as the ultimate transcriptional effectors that commit cells to enter and progress through S phase. Using conditional gene knock-out strategies, we show that E2f1-3 are not required for the proliferation of early myeloid progenitors. Rather, these E2fs are critical for cell survival and proliferation at two distinct steps of myeloid development. First, E2f1-3 are required as transcriptional repressors for the survival of CD11b(+) myeloid progenitors, and then they are required as activators for the proliferation of CD11b(+) macrophages. In bone marrow macrophages, we show that E2f1-3 respond to CSF1-Myc mitogenic signals and serve to activate E2f target genes and promote their proliferation. Together, these findings expose dual functions for E2f1-3 at distinct stages of myeloid development in vivo, first as repressors in cell survival and then as activators in cell proliferation. In summary, this work places E2f1-3 in a specific signaling cascade that is critical for myeloid development in vivo.