Association between uric acid and cardiac outcomes mediated by neutrophil-to-lymphocyte ratio in patients with left ventricular diastolic dysfunction and pulmonary hypertension.

To evaluate the association of uric acid (UA) with adverse outcomes and its potential mediator in patients with left ventricular diastolic dysfunction (LVDD) and pulmonary hypertension (PH). We retrospectively analyzed 234 patients with LVDD and PH. The baseline characteristics of patients with low UA (≤ 330 µmol/L) group were compared with high UA (> 330 µmol/L) group. Adverse outcomes included all-cause mortality, cardiac death and heart failure (HF) hospitalization. Their association with UA and the mediator were evaluated using Cox regression and mediation analysis. The mediation proportion was further quantified by the R mediation package. During a mean follow-up of 50 ± 18 months, there were 27 all-cause deaths, 18 cardiovascular deaths and 41 incidents of HF hospitalization. Multivariable Cox regression analysis showed UA was an independent risk factor of adverse outcomes in LVDD and PH patients, even after adjusting for age, sex, body mass index, medical histories, systolic blood pressure, fasting blood glucose, total cholesterol, triglyceride, eGFR, BNP and medications. The hazard ratios (HRs) for UA (per 10 µmol/L increase) were as below: for all-cause mortality, HR 1.143, 95% CI 1.069-1.221, P < 0.001; for cardiac death, HR 1.168, 95% CI 1.064-1.282, P = 0.001; for HF hospitalization, HR 1.093, 95% CI 1.035-1.155, P = 0.001. Neutrophil-to-lymphocyte ratio (NLR) played a partial mediation role in the association, and the mediation proportion for NLR on the UA-adverse outcomes were 21%, 19% and 17%, respectively. In patients of LVDD with PH, higher UA level was independently correlated with adverse outcomes. Furthermore, NLR partially mediated the effect of UA on the risk of all-cause mortality, cardiac death and HF hospitalization.

Associations of brachial-ankle pulse wave velocity with left atrial stiffness and left atrial phasic function in inpatients with hypertension.

Hypertension induces left atrial (LA) and left ventricular (LV) dysfunction, and an increase in arterial stiffness. This study aimed to investigate the associations of brachial-ankle pulse wave velocity (baPWV) with LA stiffness and LA phasic function in hypertension. A total of 305 hypertensive inpatients enrolled and were divided into two groups based on baPWV [Group I, baPWV ≤ 1515 (cm/s), n = 153; Group II, baPWV > 1515 (cm/s), n = 152]. Two-dimensional speckle tracking echocardiography (2D-STE) based LA phasic strains (LAS-S, LAS-E, LAS-A) and LV global longitudinal strain (LVGLS) were evaluated. LA stiffness index (LASI) was defined as the ratio of E/e' to LAS-S. Multivariate linear regression modeling was used to analyze the associations of baPWV with LASI and LA phasic function in all patients as well as age-specific and sex-specific subgroups. LASI was significantly higher in Group II [0.35(0.26, 0.52)] compared with Group I [0.26(0.20, 0.36)] (P < 0.001). After adjusting cardiovascular risk factors, medication, and LV structural and functional parameters (LVEF, LVMI, E/A ratio, and LVGLS), baPWV remained significantly correlated with LASI (P < 0.05). We also evaluated the predictive value of baPWV for LASI, the area under the curve (AUC) was 0.663 (95% CI: 0.607-0.716, P < 0.001). In conclusion, BaPWV was independently associated with LA stiffness in hypertensive inpatients. BaPWV also exhibited a certain predictive value for LA stiffness in these inpatients. Measuring arterial stiffness can provide clinicians clues for early cardiac target organ damage (TOD) in addition to vascular TOD.

Association Between Segmental Noninvasive Myocardial Work and Microvascular Perfusion in ST-Segment Elevation Myocardial Infarction: Implications for Left Ventricular Functional Recovery and Clinical Outcomes.

BACKGROUND: Predicting left ventricular recovery (LVR) after acute ST-segment elevation myocardial infarction (STEMI) is of prognostic importance. This study aims to explore the prognostic implications of segmental noninvasive myocardial work (MW) and microvascular perfusion (MVP) after STEMI. METHODS: In this retrospective study, 112 patients with STEMI who underwent primary percutaneous coronary intervention and transthoracic echocardiography after percutaneous coronary intervention were enrolled. Microvascular perfusion was analyzed by myocardial contrast echocardiography, and segmental MW was analyzed by noninvasive pressure-strain loops. A total of 671 segments with abnormal function at baseline were analyzed. The degrees of MVP were observed following intermittent high-mechanical index impulses: replenishment within 4 seconds (normal MVP), replenishment >4 seconds and within 10 seconds (delayed MVP), and persistent defect (microvascular obstruction). The correlation between MW and MVP was analyzed. The correlation of the MW and MVP with LVR (normalization of wall thickening, >25%) was assessed. The prognostic value of segmental MW and MVP for cardiac events (cardiac death, admission for congestive heart failure, or recurrent myocardial infarction) was evaluated. RESULTS: Normal MVP was seen in 70 segments, delayed MVP in 236, and microvascular obstruction in 365. The segmental MW indices were independently correlated with MVP; 244 (36.4%) segments had segmental LVR at 3-month follow-up. Segmental MW efficiency and MVP were independently associated with segmental LVR (P < .05). The χ2 of combination of segmental MW efficiency and MVP was higher than either index alone for identifying segmental LVR (P < .001). At a median follow-up of 42.0 months, cardiac events occurred in 13 patients; all regional MW parameters, high sensitivity troponin I, regional longitudinal strain, and so on were associated with cardiac events. CONCLUSIONS: Segmental MW indices are associated with MVP within the infarct zone following reperfused STEMI. Both are independently associated with segmental LVR, and regional MW is associated with cardiac events, providing prognostic value in STEMI patients.

Association of Nighttime Systolic Blood Pressure With Left Atrial-Left Ventricular-Arterial Coupling in Hypertension.

Objective: Hypertension (HT) induces left atrial (LA) and left ventricular (LV) dysfunction, and an increase in arterial stiffness. In this study, we investigated the association between LA-LV-arterial coupling and nighttime systolic blood pressure (BP) as well as BP circadian rhythm in essential hypertension. Methods: We enrolled 290 HT patients. All subjects were evaluated by 2- dimensional speckle tracking echocardiography (2DSTE), ambulatory 24 h BP monitoring (ABPM), and brachial-ankle pulse wave velocity (PWV). According to BP patterns, these patients were divided into two groups, which included dippers (n = 111), patients with a >10% reduction in BP at nighttime; non-dippers (n = 179), patients with a <10% reduction in BP at nighttime. 2D-STE based LA and LV strains were studied and the following parameters were measured, LV global longitudinal strain (GLS), LA reservoir strain (LAS-S), LA conduit strain (LAS-E), and LA booster pump strain (LAS-A). LA stiffness index (LASI) defined as the ratio of E/e' to LAS-S, and PWV-to-GLS ratio (PWV/GLS) were calculated to reflect LA-LV-arterial coupling. Furthermore, we also explored the correlation between LASI (or PWV/GLS) and ambulatory blood pressure indexes. Results: Left atrial stiffness index was significantly higher in non-dippers [0.29 (0.21, 0.41)] than in dippers [0.26 (0.21, 0.33)] (P < 0.05). PWV/GLS was significantly higher in non-dippers [-80.9 (-69.3, -101.5)] than in dippers [-74.2 (-60.2, -90.6)] (P < 0.05). LAS-S, LAS-E, LAS-A,and LV GLS were significantly lower in non-dippers than in dippers (P < 0.05). Multivariate linear regression analysis revealed that nighttime systolic BP was independently correlated with LASI and PWV/GLS, even adjusted for multiple clinical risk factors, LVMI, and LVEF. Conclusions: The dipping pattern of BP was related to the abnormalities of myocardial mechanics and LA-LV-arterial coupling. However, absolute nocturnal systolic BP value maybe more important than BP circadian profile in the progression of abnormal LA-LV-arterial coupling.

Evaluation of left atrial function and mechanical dispersion in breast cancer patients after chemotherapy.

BACKGROUND: Left atrial (LA) function and mechanical dispersion changes in breast cancer patients treated with chemotherapy remain unclear. HYPOTHESIS: LA function and LA mechanical dispersion in breast cancer patients would be impaired after chemotherapy. METHODS: This single-center retrospective study included 91 consecutive breast cancer patients treated with chemotherapy and 30 controls. Patients were examined by echocardiography three times at intervals. Conventional parameters, left ventricular strain, LA strain, and LA mechanical dispersion were evaluated and compared. RESULTS: LA strain during reservoir phase (LASr), conduit phase (LAScd), and contraction phase (LASct) all decreased markedly after chemotherapy and were lower than those of the controls (all p < .01). The standard deviation of time to peak positive strain during LA reservoir phase corrected by R-R interval (LA SD-TPSr) was significantly increased after chemotherapy and was higher than that of the controls (p < .001). The change of LA function was expressed as Δ. Multivariate linear regression analyses showed that LAVIp (0.399, 95% confidence interval [CI]: 0.610, 1.756, p = .000) was independently associated with ΔLASr, LAPEF (-0.325, 95% CI: -45.123, -10.676, p = .002) and age (0.227, 95% CI: 0.021, 0.350, p = .027) were independently associated with ΔLAScd, and LAVImax (0.341, 95% CI: 0.192, 0.723, p = .001) was independently associated with ΔLASct. LAVImax (0.505, 95% CI: 0.000, 0.001, p = .039) and mitral E (-0.256, 95% CI: 0.000, 0.000, p = .024）were independently associated with ΔLA SD-TPSr. CONCLUSIONS: Mechanical function of LA declined after chemotherapy in breast cancer patients. With the decrease of LA mechanical function, LA mechanical dispersion assessed by two-dimensional speckle-tracking echocardiography increased significantly, and its clinical value needs to be further studied.

Effects of blood pressure and heart rate circadian rhythms on left atrial function.

OBJECTIVE: We examined the associations among the circadian rhythms of blood pressure (BP), heart rate (HR) and left atrial function in essential hypertensive patients. METHODS: The study included 237 essential hypertensive patients who completed 24-h ambulatory BP, HR monitoring and two-dimensional speckle tracking echocardiography (2DSTE). The strain and strain rate images were studied, and the following parameters were measured: left atrial reservoir strain and strain rate (LAS-S and LASR-S), left atrial conduit strain and strain rate (LAS-E and LASR-E), and left atrial booster strain and strain rate (LAS-A and LASR-A). The left atrial stiffness index (LASI) was identified as the ratio of E/e' to LAS-S. All participants were divided into three groups according to the percentage of nocturnal BP dipping (dippers, nondippers and reverse dippers). RESULTS: The LASI was significantly higher in BP reverse dippers than in dippers and nondippers. LAS-S, LAS-E and LASR-E were significantly lower in BP reverse dippers than dippers and nondippers. Multivariate logistic regression analysis demonstrated that age, night-time mean SBP and the percentage of nocturnal HR decline were independently related to an increased LASI. CONCLUSION: Impairment of the left atrial reservoir and conduit functions was correlated with abnormal BP and HR circadian rhythms in hypertension. Increased left atrial stiffness was associated with night-time SBP and the percentage of nocturnal HR decline.

Left atrial stiffness index as a marker of early target organ damage in hypertension.

This study aimed to evaluate left atrial (LA) mechanics using two-dimensional speckle-tracking echocardiography (2DSTE) and investigate their correlations with measures of target organ damage (TOD) in hypertension. We enrolled 42 healthy controls (Group I) and 286 hypertension patients: Group II (n = 79) had an LA volume index (LAVI) <28 ml/m2; Group III (n = 92) had an LAVI ≥28 ml/m2; and Group IV (n = 115) had hypertension with left ventricular hypertrophy (LVH). We measured the following parameters: LA reservoir strain and strain rate (LAS-S, LASR-S), LA conduit strain and strain rate (LAS-E and LASR-E), and LA booster strain and strain rate (LAS-A and LASR-A). The LA stiffness index (LASI) was defined as the ratio of early diastolic transmitral flow velocity/lateral mitral annulus myocardial velocity (E/e') to LAS-S. We performed correlation and regression analyses of individual TOD with LA phasic functions, the LASI, and cardiovascular risk factors. Our findings showed that there was a trend toward a gradual increase in the LASI from controls to normal LA and enlarged LA patients and finally to hypertrophic LV patients. The LASI was significantly higher in Group III [0.28 (0.20, 0.38)] than in Group I [0.20 (0.16, 0.23)] and Group II [0.22 (0.18, 0.27)] and was the highest in Group IV [0.33 (0.26, 0.43)]. The LA reservoir and conduit function gradually decreased from Group I to Group IV. Multivariate regression analysis revealed that the LASI was independently correlated with individual TOD. In conclusion, abnormal LA mechanics precede LA enlargement and LVH, and an increased LASI can be used as a marker of early TOD in hypertension.

Comparison of cryoballoon ablation for atrial fibrillation guided by real-time three-dimensional transesophageal echocardiography vs. contrast agent injection.

BACKGROUND: Pulmonary vein (PV) occlusion generally depends on repetitive contrast agent injection when cryoballoon ablation for atrial fibrillation (AF). The present study was to compare the effect of cryoballoon ablation for AF guided by transesophageal echocardiography (TEE) vs. contrast agent injection. METHODS: Eighty patients with paroxysmal AF (PAF) were enrolled in the study. About 40 patients underwent cryoballoon ablation without TEE (non-TEE group) and the other 40 underwent cryoballoon ablation with TEE for PV occlusion (TEE group). In the TEE group during the procedure, PVs were displayed in 3-dimensional images to guide the balloon to achieve PV occlusion. The patients were followed up at regularly scheduled visits every 2 months. RESULTS: No differences were identified between the groups in regard to the procedure time and cryoablation time for each PV. The fluoroscopy time (6.7 ±â€Š4.2 min vs. 17.9 ±â€Š5.9 min, P < 0.05) and the amount of contrast agent (3.0 ±â€Š5.1 mL vs.18.1 ±â€Š3.4 mL, P < 0.05) in the TEE group were both less than the non-TEE group. At a mean of 13.0 ±â€Š3.3 mon follow-up, success rates were similar between the TEE group and non-TEE group (77.5% vs. 80.0%, P = 0.88). CONCLUSIONS: Cryoballoon ablation with TEE for occlusion of the PV is both safe and effective. Less fluoroscopy time and a lower contrast agent load can be achieved with the help of TEE for PV occlusion during procedure.

Quantitative analysis of mitral valve morphology in atrial functional mitral regurgitation using real-time 3-dimensional echocardiography atrial functional mitral regurgitation.

BACKGROUND: Atrial fibrillation (AF) can result in atrial functional mitral regurgitation (MR), but the mechanism remains controversial. Few data about the relationship between the 3-dimensional morphology of the MV and the degree of MR in AF exist. METHODS: Real-time 3-dimensional transesophageal echocardiography (3D-TEE) of the MV was acquired in 168 patients with AF (57.7% persistent AF), including 25 (14.9%) patients with moderate to severe MR (the MR+ group) and 25 patients without AF as controls. The 3-dimensional geometry of the MV apparatus was acquired using dedicated quantification software. RESULTS: Compared with the group of patients with no or mild MR (the MR- group) and the controls, the MR+ group had a larger left atrium (LA), a more dilated mitral annulus (MA), a reduced annular height to commissural width ratio (AHCWR), indicating flattening of the annular saddle shape, and greater leaflet surfaces and tethering. MR severity was correlated with the MA area (r2 = 0.43, P < 0.01) and the annulus circumference (r2 = 0.38, P < 0.01). A logistic regression analysis indicated that the MA area (OR: 1.02, 95% CI: 1.01-1.03, P < 0.01), AHCWR (OR: 0.24, 95% CI: 0.14-0.35, P = 0.04) and MV tenting volume (OR: 3.24, 95% CI: 1.16-9.08, P = 0.03) were independent predictors of MR severity in AF patients. CONCLUSIONS: The mechanisms of "atrial functional MR" are complex and include dilation of the MA, flattening of the annular saddle shape and greater leaflet tethering.

Regulation of SCN3B/scn3b by Interleukin 2 (IL-2): IL-2 modulates SCN3B/scn3b transcript expression and increases sodium current in myocardial cells.

BACKGROUND: In the initiation and maintenance of arrhythmia, inflammatory processes play an important role. IL-2 is a pro-inflammatory factor which is associated with the morbidity of arrhythmias, however, how IL-2 affects the cardiac electrophysiology is still unknown. METHODS: In the present study, we observed the effect of IL-2 by qRT-PCR on the transcription of ion channel genes including SCN2A, SCN3A, SCN4A, SCN5A, SCN9A, SCN10A, SCN1B, SCN2B, SCN3B, KCNN1, KCNJ5, KCNE1, KCNE2, KCNE3, KCND3, KCNQ1, KCNA5, KCNH2 and CACNA1C. Western blot assays and electrophysiological studies were performed to demonstrate the effect of IL-2 on the translation of SCN3B/scn3b and sodium currents. RESULTS: The results showed that transcriptional level of SCN3B was up-regulated significantly in Hela cells (3.28-fold, p = 0.022 compared with the control group). Consistent results were verified in HL-1 cells (3.73-fold, p = 0.012 compared with the control group). The result of electrophysiological studies showed that sodium current density increased significantly in cells which treated by IL-2 and the effect of IL-2 on sodium currents was independent of SCN3B (1.4 folds, p = 0.023). Western blot analysis showed IL-2 lead to the significantly increasing of p53 and scn3b (2.1 folds, p = 0.021 for p53; 3.1 folds, p = 0.023 for scn3b) in HL-1 cells. Consistent results were showed in HEK293 cells using qRT-PCR analysis (1.43 folds for P53, p = 0.022; 1.57 folds for SCN3B, p = 0.05). CONCLUSIONS: The present study suggested that IL-2, may play role in the arrhythmia by regulating the expression of SCN3B and sodium current density.

[Peripheral arterial thromboembolism in patients with non valvular atrial fibrillation: a single center case-control study].

OBJECTIVE: To explore the clinical characteristics and risk factors of peripheral arterial thromboembolism (PAT) in patients with non valvular atrial fibrillation (NVAF). METHODS: A total of 18 456 patients admitted in our hospital and diagnosed with NVAF were included in this study. The study population was divided into three groups [PAT group, cerebral thromboembolism (CT) group and no thromboembolism group]. Risk factors of PAT were assessed by multivariate logistic regression. RESULTS: The incidence of PAT and CT was 1.1% (204 cases) and 27.8% (5 132 cases), respectively. The in-hospital mortality of PAT group was 11.8% (24/204), in which the in-hospital mortality due to mesenteric arterial thromboembolism (37.5%, 6/16) was the highest. Multivariate logistic regression indicated that vascular disease (OR = 3.9, 95% CI 2.13-7.08, P < 0.01), age ≥ 65 years (OR = 2.7, 95% CI 1.66-4.27, P < 0.01), hypertension (OR = 2.1, 95% CI 1.36-3.34, P < 0.01), history of stroke/TIA/arterial thromboembolism (OR = 2.0, 95% CI 1.26-3.17, P < 0.01) and congestive heart failure (OR = 1.9, 95% CI 1.22-2.86, P < 0.01) were independent risk factors of PAT. Prevalence of vascular disease and histories of PAT was higher in PAT group than in CT group (P < 0.01), while CHADS2 and CHA2DS2VASc scores were similar between the PAT and CT groups. CONCLUSION: PAT is not uncommon in NVAF patients, risk factors for PAT in NVAF patients are vascular disease, advanced age, hypertension, history of stroke/TIA/arterial thromboembolism and congestive heart failure.