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."

Detection of cardiac involvement in pulmonary sarcoidosis using high-resolution Holter electrocardiogram.

BACKGROUND: Early detection of cardiac involvement in patients with sarcoidosis is important but currently unresolved. The aim of this study was to elucidate the utility of frequency domain microvolt T-wave alternans (TWA), signal-averaged ECG (SAECG), and heart rate turbulence (HRT) using 24-hour Holter ECG for detecting cardiac involvement in patients with pulmonary sarcoidosis. METHODS: This study consisted of consecutive 40 pulmonary sarcoidosis patients (11 males, 62 ± 13 years) who underwent 24-hour Holter monitoring with and without cardiac involvement. All patients underwent frequency domain TWA, SAECG, and HRT using 24-hour Holter monitoring. Patients with atrial fibrillation pacing or wide QRS electrocardiogram were excluded. RESULTS: After 14 patients were excluded, a total of 26 patients (six males, 59 ± 14 years) were evaluated. Seven patients had cardiac involvement (cardiac sarcoidosis [CS] group). On the Holter SAECG, duration of low-amplitude signals <40 µV in the terminal filtered QRS complex (LAS40) was significantly higher, and root mean square voltage of the terminal 40 ms of the filtered QRS complex (RMS40) was significantly lower in the CS group compared with the non-CS group (LAS40: 61.4 ± 35.9 vs 37.6 ± 9.2 ms; P = .018, RMS40: 11.4 ± 10.3 vs 23.6 ± 13.2 ms; P = .023). Prevalence of positive late potential (LP) was also significantly higher in the CS group than that in the non-CS group (85.7% vs 31.5%; P = .026). The sensitivity, specificity, positive, and negative predictive values of LP for identifying patients with cardiac involvement were 85.7%, 68.4%, 50.0%, and 92.8%, respectively. CONCLUSION: Holter SAECG may be useful for detecting cardiac involvement in patients with pulmonary sarcoidosis.

Cardiac macrophages prevent sudden death during heart stress.

Cardiac arrhythmias are a primary contributor to sudden cardiac death, a major unmet medical need. Because right ventricular (RV) dysfunction increases the risk for sudden cardiac death, we examined responses to RV stress in mice. Among immune cells accumulated in the RV after pressure overload-induced by pulmonary artery banding, interfering with macrophages caused sudden death from severe arrhythmias. We show that cardiac macrophages crucially maintain cardiac impulse conduction by facilitating myocardial intercellular communication through gap junctions. Amphiregulin (AREG) produced by cardiac macrophages is a key mediator that controls connexin 43 phosphorylation and translocation in cardiomyocytes. Deletion of Areg from macrophages led to disorganization of gap junctions and, in turn, lethal arrhythmias during acute stresses, including RV pressure overload and ß-adrenergic receptor stimulation. These results suggest that AREG from cardiac resident macrophages is a critical regulator of cardiac impulse conduction and may be a useful therapeutic target for the prevention of sudden death.

Prognostic impact of newly detected atrial fibrillation in patients with hypertrophic cardiomyopathy following cardiac implantable electronic device implantation.

Atrial fibrillation (AF) is the most common arrhythmia in patients with hypertrophic cardiomyopathy (HCM). The present study aimed to investigate the incidence and prognostic impact of newly detected AF after cardiac implantable electronic device (CIED) implantation with HCM patients. Fifty-six patients (33 men, age 57 ± 17 years) with HCM who underwent CIED implantations with no previous history of AF at the time of implantation (ICD n = 46, Pacemaker n = 10) were retrospectively enrolled. During 5.7 ± 3.6 years of follow-up, AF was newly detected in 20 (36%) of 56 patients after the CIED implantation (AF group) and the rest of the patients had no newly detected AF (non-AF group). The presence of mitral regurgitation (HR 8.49; 95% CI 2.29-30.6 P < 0.01) and concomitant NYHA II-IV (HR 3.37; 95% CI 1.30-8.86 P = 0.01) were the independent predictors of newly detected AF. During the follow-up, all patients in the AF group started anticoagulation mean 21 days after detection of AF, and none had a stroke during the follow-up period. The rate of appropriate ICD therapy (log-rank P = 0.95), inappropriate ICD therapy (log-rank P = 0.78), and all-cause death (log-rank P = 0.23) were similar between the two groups. However, the incidence of hospitalizations due to heart failure was higher in the AF group (55% vs. 6% log-rank P < 0.01). In conclusion, the incidence of newly detected AF after CIED implantations in HCM patients was high. The newly detected AF was associated with worsening heart failure and careful follow-up is recommended.

Prevalence and Significance of an Early Repolarization Electrocardiographic Pattern and Its Mechanistic Insight Based on Cardiac Magnetic Resonance Imaging in Patients With Acute Myocarditis.

BACKGROUND: An early repolarization electrocardiographic (ER-ECG) pattern is caused by various pathophysiological conditions and is reported to be a predictor of life-threatening ventricular tachyarrhythmias. However, little evidence has been reported on the prevalence and significance of the ER-ECG pattern in acute myocarditis. This study aimed to investigate the prevalence and significance of the ER-ECG pattern and its mechanistic insight based on the cardiac magnetic resonance findings in patients with acute myocarditis. METHODS: Thirty patients (23 men; 39.2±19.1 years) with a diagnosis of acute myocarditis by a clinical presentation between March 2011 and April 2018 were retrospectively evaluated. The patients were divided into 2 groups depending on the presence of an ER-ECG pattern on admission. RESULTS: Nine cases had an ER-ECG pattern, which was defined as terminal QRS notching or slurring with an amplitude of >0.1 mV in at least 2 inferior or lateral leads (early repolarization [ER] group), whereas the remaining 21 cases had broad ST-segment elevation or pathological Q waves (non-ER group). The cardiac troponin T level was significantly higher in the non-ER group than ER group (3.2±4.3 versus 0.9±1.2 ng/mL; P=0.036). The ECG changes returned to baseline along with the normalization of the cardiac biomarkers. Nine of the 21 non-ER group patients, but none of the 9 ER group patients, developed a fulminant course and lethal ventricular tachyarrhythmias. T2-weighted cardiac magnetic resonance showed high-intensity signals over the entire transmural left ventricle in the non-ER group, whereas they were localized to the left ventricular epicardium in the ER group. CONCLUSIONS: The ER-ECG pattern in acute myocarditis was transient and reversible and was not associated with a worse prognosis. Inflammation/swelling localized to the left ventricular epicardium because of acute myocarditis might provide a mechanistic insight into the ER-ECG pattern.

Electrocardiographic characteristics in the patients with a persistent left superior vena cava.

A persistent left superior vena cava (PLSVC) is a congenital venous abnormality and is usually asymptomatic and does not cause hemodynamic disturbances. Therefore, it is difficult to identify it by routine examinations in clinical practice. This study aimed to elucidate the electrocardiographic characteristics for the prediction of a PLSVC. Twelve patients (9 males, 56.2 ± 18.3 years) who were diagnosed with a PLSVC were enrolled. The electrocardiographic parameters, including the P-wave duration, axis, and morphology of the P waves, were automatically measured and compared to 150 controls (77 males, 57.3 ± 14.6 years). There were no significant differences in the P-wave duration. Negative or positive/negative P waves in lead III predicted a PLSVC with a sensitivity of 100% and specificity of 81%. The P-wave axis in PLSVC exhibited a significant leftward deviation as compared to the controls (14.8 ± 21.1 vs. 54.0 ± 17.4°, p < 0.001). A receiver operating characteristic curve analysis of the P-wave axis for predicting a PLSVC exhibited an area under curve of 0.93 [CI 95% (0.87-0.98), p < 0.001), and identified a P-wave axis of less than 37.5° to have a 92% sensitivity and 83% specificity in predicting a PLSVC. A negative or positive/negative P-wave morphology in lead III was a useful finding for suggesting the presence of a PLSVC.

Advanced interatrial block is an electrocardiographic marker for recurrence of atrial fibrillation after electrical cardioversion.

BACKGROUND: Early recurrence of atrial fibrillation (AF) is common following a successful electrical cardioversion (ECV). The purpose of this study was to investigate the hypothesis that AF recurrence is related to atrial electrical inhomogeneity, which may influence the P wave characteristics. METHODS: Two hundred ninety-one consecutive persistent AF patients who underwent ECV were enrolled, and evaluated for AF recurrences one month after the ECV. Patients with open-heart surgery, a history of catheter ablation, and an unsuccessful ECV were excluded. The P wave duration, dispersion and P wave morphology were evaluated by 12­lead ECGs 30 min after the ECV. RESULTS: In total, 141 patients were investigated. One month after the ECV, 60 (43%) patients maintained sinus rhythm. The advanced interatrial block (aIAB; P wave duration >120 ms and biphasic P waves in the inferior leads) (Hazard ratio [HR], 4.51; 95% confidence interval [CI] 1.45-14.01, P = 0.009), P wave dispersion (HR, 1.06; 95%CI 1.02-1.09, P = 0.001), and duration of AF per month (HR, 1.03; 95%CI 1.01-1.04, P = 0.004) were independent predictors of AF recurrence. An aIAB was not associated with structural parameters such as the left atrial volume index or right atrial area. There were no differences in the serum BNP level and frequency of administering anti-arrhythmic drugs between the patients with and without recurrence. CONCLUSIONS: The risk of AF recurrence after the ECV can be predicted by the P wave characteristics. A longer P wave dispersion and the duration of AF also had a tendency for recurrence.