Heart failure promotes multimorbidity through innate immune memory.

Patients with heart failure (HF) often experience repeated acute decompensation and develop comorbidities such as chronic kidney disease and frailty syndrome. Although this suggests pathological interaction among comorbidities, the mechanisms linking them are poorly understood. Here, we identified alterations in hematopoietic stem cells (HSCs) as a critical driver of recurrent HF and associated comorbidities. Bone marrow transplantation from HF-experienced mice resulted in spontaneous cardiac dysfunction and fibrosis in recipient mice, as well as increased vulnerability to kidney and skeletal muscle insults. HF enhanced the capacity of HSCs to generate proinflammatory macrophages. In HF mice, global chromatin accessibility analysis and single-cell RNA-seq showed that transforming growth factor-ß (TGF-ß) signaling was suppressed in HSCs, which corresponded with repressed sympathetic nervous activity in bone marrow. Transplantation of bone marrow from mice in which TGF-ß signaling was inhibited similarly exacerbated cardiac dysfunction. Collectively, these results suggest that cardiac stress modulates the epigenome of HSCs, which in turn alters their capacity to generate cardiac macrophage subpopulations. This change in HSCs may be a common driver of repeated HF events and comorbidity by serving as a key carrier of "stress memory."

Prediction of Atrial Fibrillation Being Asymptomatic at First Onset by Cardiac Pacing.

Asymptomatic or silent atrial fibrillation (AF) has long been a clinical problem due to the incidence of ischemic stroke. A method is needed to predict the development of silent AF before the occurrence of ischemic stroke. This study was focused on the symptoms of AF, especially palpitation, in pacemaker patients. We assessed the hypothesis that absence of palpitation during rapid ventricular pacing could be a predictor of future onset AF being asymptomatic.In this study, we assessed the presence of symptoms during RV pacing and AF symptoms on 145 pacemaker patients at the outpatient clinic by VVI pacing at 120 ppm. The relationship between symptoms during RV pacing and symptom during AF was assessed. The predictive value of absence of symptom during RV pacing on AF being asymptomatic was assessed.Of 145 patients, 74 had previous AF episode. Among the AF patients, absence of symptom during VVI pacing was associated with AF being asymptomatic.Of 145 patients, 71 had no previous AF events. There were 14 patients who had new-onset AF or atrial flutter (AFL) after the device implantation. Four of the 14 patients (28.6%) were symptomatic during first AF/AFL episode, and 10 (71.4%) were asymptomatic during first-onset AF. All ten patients who were asymptomatic during cardiac pacing test were asymptomatic during their initial episodes of AF as well.This study showed that absence of symptoms during rapid ventricular pacing was associated with first-onset AF being asymptomatic.

Two Siblings With Peripheral Pulmonary Arterial Stenosis: Pulmonary Angiography of Advanced and Early Stages.

Peripheral pulmonary arterial stenosis (PPAS) is known to cause pulmonary hypertension (PH). Although adult patients at advanced stage have been increasingly reported, there are few reports on clinical characteristics and pulmonary angiography (PAG) findings of early stage PPAS. We present two Japanese siblings with PPAS with homozygosity of RNF213 p.Arg4810Lys-one with advanced stage and the other with early stage. The latter case was an asymptomatic 37-year-old woman with mild PH. Notably, her PAG demonstrated nonthrombotic stenosis in the subsegmental branches of the pulmonary arteries with varying degrees of stenosis among lung segments. Taken together with a family history, genetic analysis, and cerebral angiography, the obtained images were considered as showing PPAS with early stage. This result is clinically informative to diagnose PPAS at an early stage and is also important to understand the pathogenesis of PPAS.

Cholecystitis and Cholangitis during Continuous Renal Replacement Therapy in a Patient with Retroperitoneal Hemorrhage Requiring Large Amounts of Contrast Medium for the Assessment and Intervention.

Intravenous use of contrast medium (CM), which may cause kidney dysfunction, is admissible for hemodialysis patients because of the efficient removal by hemodialysis. We herein report a 61-year-old woman on hemodialysis who suffered from cholecystitis and cholangitis after large-volume CM administration during continuous renal replacement therapy. After catheter ablation, she developed life-threatening retroperitoneal hemorrhage, which led to the use of 500 mL CM for 5 consecutive days. It should be kept in mind that excessive vicarious CM excretion in the biliary system may become a predisposing factor of cholecystitis and cholangitis in patients who frequently undergo radiological interventions and imaging.

The therapeutic dilemma of immunosuppressive drugs for refractory cardiac sarcoidosis in COVID-19 infection.

Patients with refractory cardiac sarcoidosis (CS) take a high dose of corticosteroid and immunosuppressive agents. During the pandemic outbreak of severe acute respiratory syndrome coronavirus 2, appropriate treatment of corticosteroids or immunosuppressive agents in CS patients with coronavirus disease 2019 (COVID-19) is unknown. Here, the woman with refractory CS receiving maintenance therapy with 15 mg of prednisolone daily and 10 mg of methotrexate weekly was emergently admitted to our hospital because of COVID-19. This case was successfully treated by the intravenous administration of dexamethasone 6 mg/day instead of prednisolone and interruption of methotrexate without resulting in recurrent life-threatening ventricular lethal arrhythmias or obvious sarcoidosis flare-ups. She started taking prednisolone and methotrexate at the maintenance dose immediately and at 2 weeks after discharge, respectively. Although the optimal regimen of immunosuppressive agents during COVID-19 is under intense debate, this report might provide an effective treatment strategy for CS patients with COVID-19.

Biventricular Thrombi Associated with Cardiac Systolic Dysfunction and Disseminated Intravascular Coagulation from Heat Stroke.

A 58-year-old man with non-ischemic cardiomyopathy visited a hospital once a month after his first hospitalization for heart failure. Three months later, he presented with consciousness impairment and heat stroke. Blood tests showed multiple organ failure, and echocardiography revealed biventricular thrombi. After admission, intensive care was provided, and anticoagulation therapy was initiated. The echocardiographic findings in the third week confirmed the complete disappearance of thrombi. Biventricular thrombi associated with disseminated intravascular coagulation from heat stroke is rare. We report the case of a patient who was treated with anticoagulation therapy only, without surgical intervention.