Effect of left bundle branch pacing on left ventricular systolic function and synchronization in patients with third-degree atrioventricular block, assessment by 3- dimensional speckle tracking echocardiography.

OBJECTIVE: To explore the effect of left bundle branch pacing (LBBP) on left ventricular systolic function and synchronization in patients with third-degree atrioventricular block. METHODS: Fifty patients with third-degree atrioventricular block from 2019- to 01-01 to 2019-6-31 in The Affiliated Hospital of Qingdao University who were eligible for pacing indications were selected. According to different pacing locations, they were randomly divided into LBBP group and right ventricular septal pacing (RVSP) group. Three-dimensional speckle tracking technology was used to collect left ventricular global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) before surgery, 6 months after surgery, 12 months after surgery, and 18 months after surgery. At the same time, the percentage of the standard deviation of the time when the left ventricular 16 segments reach the minimum systolic volume in the cardiac cycle (Tmsv16-SD/R-R) was calculated. And the QRS duration of the two groups was followed up. RESULTS: 1. GLS in LBBP group and RVSP group after surgery was significantly higher than that before surgery. And GLS in LBBP group and RVSP group showed an upward trend after surgery. However, the increase rate in LBBP group was higher than that in RVSP group. At 18 months after surgery, LBBP group was significantly higher than that in RVSP [(29.92±4.73) vs (26.48±3.80), p<0.05]. GCS in LBBP group increased gradually after surgery. GCS in RVSP group was no significant change after surgery. At 18 months after surgery, GCS in RVSP group was significantly lower than that in LBBP group [(27.92±3.37) vs (29.48±4.40), p<0.05]. There was no significant change in GRS between the two groups(p＞0.05). 2. Tmsv16-SD/R-R in LBBP group and RVSP group after surgery were lower than that before surgery (p<0.05). Tmsv16-SD/R-R in the LBBP group after surgery remained stable (P>0.05). At 18 months after surgery, Tmsv16-SD/R-R was significantly lower than that in the RVSP group [(4.27±0.67) vs (6.34±1.70), P<0.05]. 3. The QRS duration in LBBP group after surgery was significantly lower than that before surgery. And the QRS duration of the patients in the LBBP group remained stable during the 18-month follow-up (P>0.05). The QRS duration in the RVSP group after surgery had no significant change compared with that before surgery.The QRS duration in the LBBP group was significantly lower than that in the RVSP group after surgery (P＜0.05). 4. The LVEF of the LBBP group and the RVSP group remained stable after surgery, and there was no statistical difference between the two groups. CONCLUSIONS: As an emerging pacing method, LBBP has good postoperative contractility and can maintain good electromechanical synchronization.

Prognostic value of circulating tumor DNA in lymphoma: a meta-analysis.

Circulating tumor DNA (ctDNA) can be used to evaluate the prognosis of lymphoma. However, there is no uniform consensus about the mechanistic role that ctDNA plays in the prognosis of lymphoma. This meta-analysis explores the prognostic value of ctDNA in lymphoma, especially in diffuse large B cell lymphoma (DLBCL). All relevant reports published as of May 14, 2020, were retrieved by searching electronic databases in Pubmed, Embase and Cochrane Library. The prognostic value of ctDNA was evaluated using meta-analysis. Revman 5.3 software was used for prognostic data extraction and analysis. Eight studies, including a total of 767 lymphoma patients, were enrolled in this meta-analysis. Five out of eight studies investigated the association between ctDNA levels and progression-free survival (PFS) in 501 lymphoma patients, indicating that high levels of ctDNA were significantly associated with poor PFS (HR 2.24, 95%CI: 1.63-3.08, P < 0.00001). We conducted a subgroup analysis of 379 patients with DLBCL across three of the studies and came to the same conclusion (HR 2.01, 95%CI: 1.42-2.85, P < 0.0001). Two studies with a total of 192 lymphoma patients described the association between ctDNA levels and event-free survival (EFS), showing that high levels of ctDNA were also associated with adverse EFS (HR 4.53, 95%CI: 1.79-11.47, P = 0.001). The remaining two studies analyzed the potential clinical value of ctDNA for predicting the overall survival time (OS) of DLBCL patients, demonstrating that high levels of ctDNA correlated with inferior OS (HR 3.09, 95%CI: 1.50-6.35, P = 0.002). Our meta-analysis showed that high levels of ctDNA were associated with poor prognosis in patients with lymphoma, especially DLBCL.

Development and External Validation of a Nomogram for Predicting Survival in Patients With Stage IA Non-small Cell Lung Cancer ≤2 cm Undergoing Sublobectomy.

Background: Postoperative prognosis of early stage non-small cell lung cancer (NSCLC) undergoing sublobectomy is heterogeneous. Therefore, we sought to construct a novel survival prediction model for stage IA NSCLC ≤2 cm undergoing sublobectomy. Methods: Based on the data from the Surveillance, Epidemiology, and End Results (SEER) program, we successfully determined and incorporated independent prognostic markers to construct the nomogram. Internal validation of the constructed nomogram was conducted through 1,000 bootstrap resamples. The constructed nomogram was further subjected to external validation with an independent cohort of patients from two Chinese institutions. The performance of the survival prediction model was assessed by concordance index, calibration plots, and risk subgroup classification. Results: A total of 3,238 patients from SEER registries (development cohort), as well as 769 patients from two Chinese institutions (validation cohort) was included. Gender, age, size, histologic type, grade, and examined lymph nodes count were identified as significant prognostic parameters. A novel nomogram was developed and externally validated. Concordance index of constructed nomogram was significantly better than that of the current TNM staging system. Calibration plots demonstrated an optimal consistency between the nomogram predicted and actual observed probability of survival. Survival curves of different risk subgroups within respective TNM stage demonstrated significant distinctions. Conclusion: We developed and externally validated a survival prediction model for patients with stage IA NSCLC ≤2 cm undergoing sublobectomy. This novel nomogram outperforms the conventional TNM staging system and could help clinicians in postoperative surveillance and future clinical trial design.

Long non-coding RNA CHRF facilitates cardiac hypertrophy through regulating Akt3 via miR-93.

BACKGROUND: Non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been demonstrated as central mediators in cardiac hypertrophy responses. LncRNA cardiac hypertrophy related factor (CHRF) has been reported to be implicated in cardiac hypertrophy. However, the underlying mechanisms of CHRF have not been thoroughly elucidated. METHODS: Expressions of CHRF and microRNA-93 (miR-93) in heart tissues and cardiomyocytes were detected by RT-qPCR assay. Cell surface area, protein/DNA ratio, atrial natriuretic peptide (ANP) and ß-myosin heavy chain (ß-MHC) levels were examined as the indicators of cardiac hypertrophy responses. Luciferase reporter assay was used to validate the direct binding between miR-93 and CHRF or Akt3 3'UTR. RIP assay was performed to demonstrate the potential interaction between CHRF and miR-93. Akt3 protein level was determined by western blot assay. RESULTS: CHRF expression was up-regulated and miR-93 expression was down-regulated in mice and cellular models of cardiac hypertrophy. CHRF knockdown attenuated isoproterenol (Iso)-induced hypertrophy responses through up-regulating miR-93 expression in cardiomyocytes. Moreover, CHRF acted as a competing endogenous RNA of miR-93 to sequester miR-93 from Akt3, resulting in the increase of Akt3 expression. Furthermore, miR-93 suppressed cardiac hypertrophy responses by targeting Akt3 in Iso-stimulated cardiomyocytes. CONCLUSIONS: CHRF induced cardiac hypertrophy by regulating miR-93/Akt3 axis in Iso-stimulated cardiomyocytes, deepening our understanding of the molecular mechanisms of lncRNAs in cardiac hypertrophy and providing a potential therapy target for cardiac hypertrophy.

Clusterin Reduces Cold Ischemia-Reperfusion Injury in Heart Transplantation Through Regulation of NF-kB Signaling and Bax/Bcl-xL Expression.

BACKGROUND/AIMS: Ischemia-reperfusion (I/R) injury is an unavoidable event occurring during heart transplantation and is a key factor in graft failure and the long-term survival rate of recipients. Therefore, there is an urgent need for the development of new therapies to prevent I/R injury. Clusterin is a hetero-dimeric glycoprotein with an antiapoptotic function. In this study, we investigated whether clusterin was cardioprotective in heart transplantation against I/R injury using an in vivo rat model and an in vitro cell culture system, and examined the underlying mechanisms of I/R injury. METHODS: Heart grafts from wild-type C57BL/6 mice were preserved in UW solution (control) or UW solution containing recombinant human apolipoprotein-J (hr clusterin) for 24 h. The preserved hearts were implanted into recipient mice of the same strain as the donors for 72 h, and the heart grafts were then taken for histopathological and gene expression analyses. An in vitro ischemia reperfusion model using H9C2 cells or H9C2/clusterin cDNA cells was constructed. The expression of clusterin, p65, Bax, Bcl-xL, IL-1ß, and TNF-α protein and mRNA in heart tissue and H9C2 cells was detected by western blot, reverse transcription-polymerase chain reaction (RT-PCR), and quantitative RT-PCR assays; IL-1ß and TNF-α protein was detected by enzyme-linked immunosorbent assays; NF-kB activity was detected by an electrophoretic mobility shift assay; cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and flow cytometric analyses. RESULTS: Cold I/R caused severe morphologic myocardial injury to heart grafts from wild-type C57BL/6 mice, whereas grafts from hr clusterin preservation showed less damage, as demonstrated by decreased cell apoptosis/death, decreased neutrophil infiltration, and the preservation of the normal structure of the heart. Clusterin reduced the expression of p65, pre-inflammatory IL-1ß, and TNF-α, and the pro-apoptotic gene Bax, while it enhanced the expression of the anti-apoptotic gene Bcl-xL in vitro and in vivo. Clusterin inhibited cell apoptosis/death and reduced pre-inflammatory. CONCLUSION: Clusterin is a promising target for preventing cold I/R injury in heart transplantation. This study also shows that the resultant protective effects of clusterin are mediated by NF-κB signaling and Bax/Bcl-xL expression.

Evaluation of cardiac function by pacing at different right ventricular sites in patients with third-degree atrioventricular block using Doppler ultrasound.

OBJECTIVE: This study utilized Doppler ultrasonography cardiograms in patients with third-degree atrioventricular (III-AV) block to compare right ventricular apex (RVA) pacing and right ventricular outflow tract (RVOT) pacing with respect to their effects on synchronization of contraction between the two ventricles, as well as on timing of specific left-ventricular electrical and mechanical events and their impact on left ventricular function. METHODS: Thirty-eight patients with (III-AV) block were implanted with dual-chamber pacemakers, in 20 cases, implantation occurring in the RVOT (RVOT group), while in 18 cases implantation occurred in the RVA (RVA group). Patients underwent Doppler echocardiography and electrocardiography (ECG) one month pre- and one month post-surgery, as well as 12 months post-surgical implantation of the pacemaker. RESULTS: Prior to pacemaker implantation, no significant differences were found between the two groups with respect to the following parameters: left ventricular end-diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF), E/A value (ratio of early [E] to late [A] ventricular filling velocities), inter-ventricular mechanical delay (IVMD)and septal-to-posterior wall motion delay (SPWMD). One month after implantation, no significant differences were found between the two groups for LVEDD, LVESD, LVEF, and E/A. However, compared with the RVOT group, the RVA group exhibited prolonged IVMD and SPWMD. Twelve months after pacemaker implantation, there was no significant difference for E/A between the two groups; however, compared with the ROVT group, the RVA group exhibited prolonged LVEDD, LVESD, IVMD, and SPWMD and significantly lower LVEF. CONCLUSION: Relative to RVA pacing, RVOT pacing mitigated impairment of systolic function and systolic dys-synchronization.

Echocardiography for determining the optimal atrioventricular interval in patients with dual chamber pacemakers.

BACKGROUND: We investigated the clinical value of Doppler echocardiography for determining the optimal setting of atrioventricular interval in patients with dual chamber pacemakers (DDD). In 38 patients with complete atrioventricular block and DDD pacemakers, the atrioventricular interval was prolonged in a stepwise fashion by 20 ms, from 90 to 250 ms, and cardiac stroke volume and transmitral flow were measured by pulsed Doppler echocardiography. METHODS: The optimal atrioventricular interval at which the cardiac stroke volume was maximal was 168.9 +/- 15.6 ms. The atrioventricular interval was 178.4 +/- 23.4 ms when the end of the A wave coincided with complete closure of the mitral valve. RESULTS: There was a significant linear relationship between the optimal atrioventricular interval and the predicted optimal atrioventricular interval (Y = 86.2 +/- 0.5X, r = 0.70, standard error of the estimate [SEE] = 11.5, P < 0.01). CONCLUSION: The optimal atrioventricular interval setting for DDD pacing can be successfully determined using Doppler echocardiography, which is a noninvasive, repeatable, and simple approach.

Prognostic value of high-sensitivity C-reactive protein in patients with chronic heart failure.

OBJECTIVE: To determine whether high-sensitivity C-reactive protein (hsCRP) has prognostic value in patients with chronic heart failure. METHODS: Serum hsCRP levels were measured with high-sensitivity assay (IMMAGE Immunochemistry Systems) in 128 patients with CHF and 25 healthy control subjects. Cardiac troponin T (TNT) was measured by electrochemiluminescence immunoassay on an Elecsys1010 automatic analyser. Cardiac events were defined as cardiac death and rehospitalisation because of worsening heart failure during the follow-up period. RESULTS: Circulating levels of hsCRP and TNT were significantly higher in patients with CHF than in the 25 healthy people (p=0.0028, p=0.017, respectively) and increased with severity of CHF. During a mean follow-up period of 378 +/- 26 days, 42 (32.8%) of the 128 patients had cardiac events. Levels of hsCRP and TNT were significantly higher (p=0.00031, p=0.00047, respectively) and LVEF was significantly lower (p=0.0052) in patients with cardiac events than in patients without cardiac events. When multivariate Cox proportional hazards regression was performed, we found that hsCRP, TNT, and LVEF were independent significant predictors of cardiac events in patients with CHF (hsCRP: hazard ratio [HR], 3.81; 95% confidence interval [CI], 2.14-9.35; p=0.024; TNT: HR, 2.61; 95%CI, 1.96-4.31; p=0.012; LVEF: HR, 3.52; 95%CI, 2.36-10.37; p=0.024). When Pearson's correlation analyses were performed, we could find a positive correlation between hsCRP and TNT (r=0.493, p=0.0043) and a negative correlation between hsCRP and LVEF(r=-0.354, p=0.0051). CONCLUSION: Serum hsCRP concentrations were elevated in patients with CHF and increased with severity of CHF. It was an independent significant predictor of cardiac events in patients with CHF.

Clinical significance of serum cardiac troponin T in patients with congestive heart failure.

OBJECTIVE: To determine whether the level of serum cardiac troponin T (cTnT) was increased in patients with congestive heart failure (CHF). METHODS: This study consisted of 265 patients with CHF and 75 healthy people. Serum cTnT was measured by electrochemiluminescence immunoassay using an Elecsys 1010 automatic analyzer. RESULTS: cTnT concentration was 0.181 +/- 0.536 ng/mL in CHF patients and 0.003 +/- 0.001 ng/mL in controls (P < 0.001). Patients were categorized according to the levels of heart function and left ventricular ejection fraction (LVEF). In the first group consisting of 105 patients with LVEF 35%, cTnT was 0.07 +/- 0.0 5 ng/mL (P < 0.01). In patients with NYHA class I, II, III and IV, cTnT values were 0.062 +/- 0.022 ng/mL, 0.113 +/- 0.121 mg/mL, 0.191 +/- 0.231 mg/ml and 0.384 +/- 0.211 mg/mL, respectively (class I vs class II P > 0.05, class II vs class III P < 0.01, class III vs class IV P < 0.01). A negative correlation was observed between serum cTnT concentration and LVEF in 265 patients with CHF (r = -0.493, P < 0.001). CONCLUSIONS: This study shows that the level of serum cTnT is increased in patients with CHF and that the increased level indicates the severity of CHF.