Predictive value of early-phase heart rate reduction for subsequent recovery of left ventricular systolic function in heart failure with reduced ejection fraction.

INTRODUCTION: Predictors of heart failure with recovered ejection fraction (HFrecEF) remain to be fully elucidated. This study investigated the impact of heart rate and its change on the recovery of left ventricular ejection fraction (LVEF) in heart failure with reduced ejection fraction (HFrEF). MATERIAL AND METHODS: From 398 outpatients who had a history of hospitalisation for heart failure, 138 subjects diagnosed as HFrEF (LVEF < 40%) on heart failure hospitalisation were enrolled and longitudinally surveyed. During follow-up periods more than one year, 64 and 46 patients were identified as HFrecEF (improved LVEF to ≥ 40% and its increase of ≥ 10 points) and persistent HFrEF, respectively. RESULTS: In the overall subjects, the reduction of heart rate through the observation periods was closely correlated with the improvement of LVEF (r = -0.508, p < 0.001). Heart rate on hospital admission for heart failure was markedly higher in patients with HFrecEF (112 ± 26 bpm) than in those with persistent HFrEF (90±18 bpm). Whereas heart rate at the first outpatient visit after discharge was already lower in the HFrecEF group (80 ± 13 vs. 85 ± 13 bpm in the persistent HFrEF group). A multivariate logistic regression analysis revealed that the decrease in heart rate from admission to the first visit after discharge was a significant determinant of HFrecEF (p < 0.001), independently of confounding factors such as ischemic heart disease and baseline LVEF and left ventricular dimension. CONCLUSIONS: Our findings suggest that heart rate reduction in the early phase after heart failure onset is a powerful independent predictor of the subsequent recovery of LVEF in HFrEF patients.

Exosomal miR206 Secreted From Growing Muscle Promotes Angiogenic Response in Endothelial Cells.

BACKGROUND: Resistance exercise is beneficial in patients with lower extremity arterial disease. Muscle-derived exosomes contain many types of signaling molecules, including microRNAs (miRNAs). Here, we tested the hypothesis that exosomal miRNAs secreted by growing muscles promote an angiogenic response in endothelial cells (ECs).Methods and Results: Skeletal muscle-specific conditional Akt1 transgenic (Akt1-TG) mice, in which skeletal muscle growth can be induced were used as a model of resistance training. Remarkable skeletal muscle growth was observed in mice 2 weeks after gene activation. The protein amount in exosomes secreted by growing muscles did not differ between Akt1-TG and control mice. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway frequency analysis of 4,665 target genes, identified using an miRNA array miRNAs, revealed a significant increase in Akt and its downstream signaling pathway genes. Among the upregulated miRNAs, miR1, miR133, and miR206 were significantly upregulated in the serum of Akt1-TG mice. miR206 was also increased in insulin-like growth factor (IGF)-1-stimulated hypertrophied myotubes. Exogenous supplementation of exosomal miR206 to human umbilical vein ECs promoted angiogenesis, as assessed using the spheroid assay, and increased the expression of angiogenesis-related transcripts. CONCLUSIONS: Exosomal miR206 is upregulated in the blood of Akt1-TG mice and in IGF-stimulated cultured myotubes. Exogenous supplementation of miR206 promoted an angiogenic response in ECs. Our data suggest that miR206 secreted from growing muscles acts on ECs and promotes angiogenesis.

Quantification of pulmonary perfusion using LSIM-CT correlates with pulmonary hemodynamics in patients with CTEPD.

Background: Lung subtraction iodine mapping (LSIM)-CT is a clinically useful technique that can visualize pulmonary mal-perfusion in patients with chronic thromboembolic pulmonary disease (CTEPD). However, little is known about the associations of LSIM images with hemodynamic parameters of patients with CTEPD. This study investigates a parameter of LSIM images associated with mean pulmonary arterial pressure (mPAP) and validates the association between pulmonary vascular resistance, right atrial pressure, cardiac index, and exercise capacity in patients with CTEPD. Methods: This single-center, prospective, observational study involved 30 patients diagnosed with CTEPD using lung perfusion scintigraphy. To examine the correlation of decreased pulmonary perfusion area (DPA) with mPAP, areas with 0-10, 0-15, 0-20, and 0-30 HU in lung subtraction images were adopted in statistical analysis. The DPA to total lung volume ratio (DPA ratio, %) was calculated as the ratio of each DPA volume to the total lung volume. To assess the correlation between DPA ratios of 0-10, 0-15, 0-20, and 0-30 HU and mPAP, Spearman's rank correlation coefficient was used. Results: The DPA ratio of 0-10 HU had the most preferable correlation with mPAP than DPA ratios of 0-15, 0-20, and 0-30 HU (ρ = 0.440, P = 0.015). The DPA ratio of 0-10 HU significantly correlates with pulmonary vascular resistance (ρ = 0.445, P = 0.015). The receiver operating characteristic curve analysis indicated that the best cutoff value of the DPA ratio of 0-10 HU for the prediction of an mPAP of ≥30 mmHg was 8.5% (AUC, 0.773; 95% CI, 0.572-0.974; sensitivity, 83.3%; specificity, 75.0%). Multivariate linear regression analysis, which was adjusted for the main pulmonary arterial to ascending aortic diameter ratio and right ventricular to left ventricular diameter ratio, indicated that the DPA ratio of 0-10 HU was independently and significantly associated with mPAP (B = 89.7; 95% CI, 46.3-133.1, P < 0.001). Conclusion: The DPA ratio calculated using LSIM-CT is possibly useful for estimating the hemodynamic status in patients with CTEPD.

The E/e' ratio on echocardiography as an independent predictor of the improvement of left ventricular contraction in patients with heart failure with reduced ejection fraction.

OBJECTIVE: Clinical feature of heart failure with improved ejection fraction (HFimpEF) remains to be fully elucidated. The present study investigated the association of clinical and echocardiographic parameters with the subsequent improvement of left ventricular ejection fraction (LVEF) in heart failure with reduced ejection fraction (HFrEF). METHODS: From outpatients with a history of hospitalized for heart failure, 128 subjects diagnosed as HFrEF (LVEF <40%) on heart failure hospitalization were enrolled and longitudinally surveyed. During follow-up periods more than 1 year, 58 and 42 patients were identified as HFimpEF (improved LVEF to ≥40% and its increase of ≥10 points) and persistent HFrEF, respectively. RESULTS: There was no difference in age or sex between the two groups with HFimpEF and persistent HFrEF. The rate of ischemic heart disease was lower and that of tachyarrhythmia was higher in the HFimpEF group than in the persistent HFrEF group. At baseline (i.e., on heart failure hospitalization), LVEF did not differ between the two groups, but left ventricular systolic and diastolic diameters were already smaller and the ratio of early diastolic transmitral velocity to early diastolic tissue velocity (E/e') was lower in the HFimpEF group. A multiple logistic regression analysis revealed that lower baseline E/e' was a significant determinant of HFimpEF, independently of confounding factors such as ischemic heart disease, tachyarrhythmia, and baseline left ventricular dimension. CONCLUSION: Our findings indicate that the lower ratio of E/e' in the acute phase of heart failure onset is an independent predictor of the subsequent improvement of LVEF in HFrEF patients.

Vaso reactivity test using inhaled nitric oxide for pulmonary arterial hypertension accompanied by severe interstitial lung disease attributed to systemic sclerosis: A case report.

A 70-year-old man with severe interstitial pneumonia attributed to limited cutaneous systemic sclerosis was referred to our institution because of worsening dyspnea. High-resolution computed tomography did not show considerable progression compared with previous images, whereas transthoracic echocardiography showed severe right ventricular dysfunction. Oxygen saturation was decreased to 84% at room air. A blood test showed an increase in the plasma brain natriuretic peptide level (289.4 pg/mL). Right heart catheterization (RHC) showed a remarkably high mean pulmonary arterial pressure (mPAP) of 48 mmHg at room air. A vaso reactivity test using inhaled nitric oxide showed improvement of mPAP, pulmonary vascular resistance (PVR), and partial pressure of arterial oxygen. These findings suggested that the patient responded to pulmonary hypertension (PH)-targeted drugs. We then prescribed tadalafil 10 mg and inhaled iloprost 5 µg six times daily. Three weeks after initiating PH-targeted drugs, RHC indicated hemodynamic improvement similar to hemodynamic changes in the vaso reactivity test (mPAP: 28 mmHg; PVR: 4.2 W.U.). He was discharged with improved symptoms. Inhaled nitric oxide during RHC might be helpful to consider the treatment strategy when patients have PH comorbid systemic sclerosis and severe interstitial lung disease. .

Dynapenia is an independent predictor of cardio-cerebrovascular events in patients undergoing hemodialysis.

The number of patients on maintenance hemodialysis (HD) diagnosed with sarcopenia has been increasing through as individuals age. Recent focus is on the condition termed, "dynapenia," which reduces only muscle function, as opposed to sarcopenia, which reduces both muscle mass and function. However, the association between dynapenia and cardio-cerebrovascular (CV) events in patients undergoing HD is largely unknown. The purpose of this study was to evaluate whether sarcopenia and dynapenia are associated with the onset of CV events in patients undergoing HD. We retrospectively analyzed 342 patients undergoing HD between January and December 2018. Patients who underwent HD thrice per week for > 3 months were included in the analysis. We adopted the Asian Working Group on Sarcopenia criteria for the diagnosis of sarcopenia and dynapenia. In this study, 244 patients undergoing HD were enrolled. The prevalence of sarcopenia was 38.5%. Sarcopenia was determined to be an independent contributor to CV events in patients undergoing HD. To investigate the clinical relevance of dynapenia in patients with HD, patients without sarcopenia were further divided into dynapenia and non-dynapenia groups. Among 150 patients without sarcopenia, 46 were diagnosed with dynapenia. In the Kaplan-Meier analysis, the rate of CV events was significantly different among the three groups in a stratified manner, with the highest rate in the sarcopenia group and the lowest rate in the non-sarco-dynapenia group. Both patients with sarcopenia and dynapenia had significantly increased CV events compared to those with non-sarco-dynapenia (HR 8.00; 95% CI 2.73-34.1; p < 0.0001 vs. HR 4.85; 95% CI 1.28-23.0; p < 0.02). Both sarcopenia and dynapenia resulted in significantly higher CV events than non-sarco-dynapenia in patients undergoing HD. Therefore, clinicians should evaluate muscle function in addition to muscle quantity to estimate CV events in patients undergoing HD.

Angioscopic Ulcerated Plaques in the Femoropopliteal Artery Associated with Impaired Infrapopliteal Runoff.

PURPOSE: To determine the correlation between upstream atherosclerosis in the femoropopliteal arteries, assessed using angioscopy, and impaired infrapopliteal runoff. MATERIALS AND METHODS: Thirty-one patients with peripheral arterial disease who underwent endovascular therapy and angioscopy were prospectively included. Yellow plaque color scores were semiquantitatively determined as 0, 1, 2, or 3. Irregular plaques with rough surfaces, similar to gastric ulcers, were defined as ulcerated plaques (UPs). Angioscopic data were correlated with angiographic runoff scores (ARS). RESULTS: UPs were detected in 74.2% of enrolled diseased legs using angioscopy. Mural thrombi were more commonly observed in the femoropopliteal artery in patients with UPs than in those without UPs (91.3% vs 37.5%, respectively; P = .006) and were frequently found on the UPs (21/23 patients with UPs). Univariate and multivariate linear regression analyses revealed that the presence of UPs was positively and independently associated with a poor ARS and that oral anticoagulant use was independently associated with a preferable ARS (standardized ß = 0.462, P = .004 and standardized ß = -0.411, P = .009, respectively, in the multivariate analysis). CONCLUSIONS: UPs, associated with mural thrombi and diagnosed by angioscopic examination, were demonstrated to be one of the factors associated with poor infrapopliteal runoff.