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 pacemaker-induced cardiomyopathy using a convolutional neural network based on clinical findings prior to pacemaker implantation.

Risk factors for pacemaker-induced cardiomyopathy (PICM) have been previously reported, including a high burden of right ventricular pacing, lower left ventricular ejection fraction, a wide QRS duration, and left bundle branch block before pacemaker implantation (PMI). However, predicting the development of PICM remains challenging. This study aimed to use a convolutional neural network (CNN) model, based on clinical findings before PMI, to predict the development of PICM. Out of a total of 561 patients with dual-chamber PMI, 165 (mean age 71.6 years, 89 men [53.9%]) who underwent echocardiography both before and after dual-chamber PMI were enrolled. During a mean follow-up period of 1.7 years, 47 patients developed PICM. A CNN algorithm for prediction of the development of PICM was constructed based on a dataset prior to PMI that included 31 variables such as age, sex, body mass index, left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left atrial diameter, severity of mitral regurgitation, severity of tricuspid regurgitation, ischemic heart disease, diabetes mellitus, hypertension, heart failure, New York Heart Association class, atrial fibrillation, the etiology of bradycardia (sick sinus syndrome or atrioventricular block) , right ventricular (RV) lead tip position (apex, septum, left bundle, His bundle, RV outflow tract), left bundle branch block, QRS duration, white blood cell count, haemoglobin, platelet count, serum total protein, albumin, aspartate transaminase, alanine transaminase, estimated glomerular filtration rate, sodium, potassium, C-reactive protein, and brain natriuretic peptide. The accuracy, sensitivity, specificity, and area under the curve of the CNN model were 75.8%, 55.6%, 83.3% and 0.78 respectively. The CNN model could accurately predict the development of PICM using clinical findings before PMI. This model could be useful for screening patients at risk of developing PICM, ensuring timely upgrades to physiological pacing to avoid missing the optimal intervention window.

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.

Association of Baseline Anemia with Mid-Term Clinical Outcomes in Patients Who Underwent Trans-Radial Primary Percutaneous Coronary Intervention.

Radial access is recommended for primary percutaneous coronary intervention (PCI), because it has fewer bleeding complications than trans-femoral PCI. However, even if trans-radial PCI is chosen, patients with ST-elevation myocardial infarction (STEMI) presenting with anemia on admission might have poor clinical outcomes. The aim of this retrospective study was to investigate whether anemia on admission was associated with mid-term clinical outcomes in patients who underwent trans-radial primary PCI. The primary endpoint was a composite of all-cause death, recurrent acute myocardial infarction, and readmission for heart failure. A total of 288 consecutive patients with STEMI who underwent trans-radial primary PCI were divided into an anemia group (n = 79) and a non-anemia group (n = 209). The median follow-up duration was 301 days. The anemia group was significantly older than the non-anemia group (77.3 ± 11.9 versus 64.4 ± 12.7 years, respectively; P < 0.001). There were significantly more females in the anemia group than in the non-anemia group (36.7% versus 14.4%, respectively; P < 0.001). Kaplan-Meier analysis revealed that the composite outcome-free survival was significantly worse in the anemia group than in the non-anemia group (P < 0.001). Multivariate Cox hazard model analysis revealed that hemoglobin levels on admission were significantly associated with the composite outcome (per 1 g/dL increase: hazard ratio 0.76, 95% confidence interval 0.66-0.88, P < 0.001) after controlling for confounding factors. In conclusion, baseline anemia was significantly associated with poor clinical outcomes. Patients with STEMI presenting with anemia should be managed carefully, even if trans-radial primary PCI is chosen.

Usefulness of 500-m walk electrocardiogram test on clinical outcomes in patients with ST-segment elevation myocardial infarction.

The current Japanese guideline for ST-segment elevation myocardial infarction (STEMI) recommends 500-m walk electrocardiogram (ECG) test for patients with STEMI during hospitalization. However, little is known regarding the association between acute phase 500-m walk ECG test and clinical outcomes. The purpose of this study was to investigate the association between 500-m walk ECG test and mid-term clinical outcomes in patients with STEMI. A total of 313 STEMI patients who underwent primary percutaneous coronary interventions were included, and were divided into the successful 500-m group (n = 263) and the unsuccessful 500-m group (n = 50). The primary endpoint was the major adverse cardiovascular events (MACE), which were defined as the composite of all cause death, acute myocardial infarction, readmission for heart failure, and ischemia-driven target vessel revascularization (TVR). During the follow-up period (median 223 days), a total of 55 MACE were observed. The log-rank test revealed that MACE, all cause death, readmission for heart failure, and ischemia-driven TVR were more frequently observed in the unsuccessful 500-m group than the successful 500-m group. In the multivariate Cox proportional hazard model, the unsuccessful 500-m walk ECG test was significantly associated with MACE (OR 5.62, 95% CI 3.08-10.08, P < 0.01) after controlling confounding factors such as age, and serum creatinine levels. In conclusion, the unsuccessful 500-m walk ECG test was significantly associated with poor mid-term outcomes in patients with STEMI. Our results suggest the usefulness of 500-m walk ECG test to stratify the high-risk group from patients with STEMI.