Chromogranin A as a diagnostic marker of pheochromocytoma and paraganglioma: A systematic review and meta-analysis.

OBJECTIVES: This work aims to assess the diagnostic value of chromogranin A (CgA) in the laboratory diagnosis of neuroendocrine tumors classified as pheochromocytoma and paraganglioma (PPGL). METHODS: A comprehensive search was performed in PubMed, Embase, the Cochrane Library, and Web of Science databases to obtain relevant studies reporting the diagnostic accuracy of CgA in patients with PPGL. The search involved studies written in English between the time of library inception and May 1, 2023. We computed the pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Additionally, the receiver operating characteristic curve and area under the curve (AUC) were determined. The heterogeneity was assessed using the Chi-square test and the I2 test. The subgroup analyses were performed to investigate the origins of heterogeneity. Stata 15.1 statistical software was used in all data analyses. RESULTS: This meta-analysis included 13 studies involving 1470 patients. CgA had a pooled diagnostic sensitivity of 0.86 (95% CI 0.81-0.91), a specificity of 0.90 (95% CI 0.81-0.95), and a DOR of 57 (95% CI 23-142). CgA had an AUC of 0.93. The studies did not reveal any threshold effect (r = -0.165; p > 0.05). The subgroup analyses revealed that the control group category and the detection method caused the overall heterogeneity. CONCLUSIONS: Our study suggests that CgA is a helpful PPGL biomarker. However, relying solely on CgA for diagnosis is not advisable. A comprehensive approach is essential for accurate diagnosis. Future large-scale research is needed to refine CgA's clinical application.

Donor-derived cell-free DNA as a diagnostic marker for kidney-allograft rejection: A systematic review and meta-analysis.

Donor-derived cell-free DNA (dd-cfDNA) has emerged as a promising biomarker for detecting graft rejection. This study aimed to evaluate the diagnostic accuracy and clinical value of applying it to kidney transplant rejection. Relevant literature on dd-cfDNA diagnostics in kidney transplant rejection was reviewed from PubMed, Embase, Cochrane Library, and Web of Science databases up to 2023. Data and study characteristics were extracted independently by two researchers, and disagreements were resolved through discussion. Diagnostic accuracy data for any rejection (AR) and antibody-mediated rejection (ABMR) were analyzed separately. Potential heterogeneity was analyzed by subgroup analysis or meta-regression. Funnel plots were used to clarify the presence or absence of publication bias. Nine publications provided data on dd-cfDNA accuracy in diagnosing patients with AR. The pooled sensitivity, specificity, and the area under the receiver operating characteristic (AUROC) curve with 95% confidence intervals (CI) were 0.59 (95% CI, 0.48-0.69), 0.83 (95% CI, 0.76-0.88), and 0.80 (95% CI, 0.76-0.83), respectively. Additionally, 12 studies focused on the diagnostic accuracy of dd-cfDNA for ABMR, showing pooled sensitivity, specificity, and the AUROC curve with 95% CI of 0.81 (95% CI, 0.72-0.88), 0.80 (95% CI, 0.73-0.86), and 0.87 (95% CI, 0.84-0.90), respectively. Study type, age group, and sample size contributed to heterogeneity. In summary, our findings indicate that while plasma dd-cfDNA accuracy in diagnosing patients with AR is limited by significant heterogeneity, it is a valuable biomarker for diagnosing ABMR.

Right ventricular outflow pacing induces less regional wall motion abnormalities in the left ventricle compared with apical pacing.

AIMS: This study aimed to explore if the right ventricular outflow tract (RVOT) pacing is superior to right ventricular apical (RVA) pacing on the overall left ventricular (LV) function and regional wall motion. METHODS AND RESULTS: Sixty patients with atrio-ventricular (AV) block and normal ejection fraction undergoing dual-chamber pacemaker implantation were randomized to permanent ventricular stimulation either in the RVOT or the RVA. Left ventricular volume, ejection fraction, and LV regional wall motion were assessed by echocardiography. Right ventricular apical pacing had prolonged QRS duration, compared with RVOT pacing (154.1 ± 26.5 vs. 120.9 ± 22.3, P< 0.05). There were also significant differences in LV pre-ejection interval and interventricular mechanical delay (IVMD) at 12-month follow-up between the two groups, but none in the LV volume, left ventricular ejection fraction, and index of systolic synchrony (Ts-SD). During RVA pacing, the average peak systolic velocity (Sm) of 12 LV segments [3.5, 95% confidence interval (CI) 3.2-3.8 cm/s] had a trend of being lower compared with RVOT pacing (3.9, 95% CI 3.5-4.1 cm/s) (P= 0.09). Further analysis showed that the Sm at the inferior wall and posterior-septum wall was significantly decreased during RVA pacing compared with RVOT pacing. There were no significant differences for other LV segments. CONCLUSION: The RVOT pacing in AV block patients over 1 year may be superior to RVA pacing in terms of regional LV performance, LV global electromechanical delay, and IVMD, although intraventricular dyssynchrony and LV volumes do not differ. Larger trials with clinical endpoints are warranted to conclusively define the advantages of RVOT or RV septal pacing.

[Effects of integrated disease management program on the outcome of patients with heart failure].

OBJECTIVE: To investigate the feasibility and efficacy on the outcome of patients with heart failure of integrated disease management program with heart failure clinic, patient education and telephone follow-up. METHODS: A total of 145 hospitalized patients with chronic heart failure and LVEF ≤ 45% or patients with LVEF > 45% and NT-proBNP > 1500 ng/L were divided into conventional group (n = 71) and interventional group (n = 74). Patients were followed for 10 to 12 months. RESULTS: Baseline clinical characteristics, LVEF and dose of evidence-based medicine were similar between the 2 groups. During follow-up, the NYHA functional class was higher in conventional group than interventional group (3.2 ± 0.5 vs 1.4 ± 0.5, P < 0.05), and the LVEF deteriorated in the conventional group and improved from 34% to 40%in the interventional group. The proportions of self-monitoring of weight, blood pressure and pulse rate in the interventional group were significantly higher than those of conventional group (P < 0.05). Among patients with systolic heart failure, 40% patients in the interventional group and 11% patients in the conventional group achieved the target doses of ß-blockers (P < 0.05). Cardiovascular event rate of conventional group and interventional group is 91.5% and 27.0% respectively (P < 0.05). CONCLUSION: Integrated disease management program with heart failure clinic, patient education and telephone follow-up can improve patient compliance to heart failure treatment, improve cardiac function and reduce cardiovascular event rate.

[Factors associated with efficacy of cardiac resynchronization therapy for patients with congestive heart failure].

OBJECTIVE: The efficacy of cardiac resynchronization therapy (CRT) in patients with congestive heart failure and the potential factors associated with responder or nonresponder were investigated. METHODS: Fifty three patients with congestive heart failure (42 with sinus rhythm and 11 with atrial fibrillation) underwent CRT were enrolled in this study. Conventional echocardiography and tissue Doppler imaging were performed in each patient before implantation and 6 month post implantation. Clinical response was defined as improvement of one NYHA functional class and echocardiographic response was defined as a reduction in LV end-systolic volume by > 15% or an increase of absolute value of LVEF > 5%. RESULTS: The clinical response rate was 75% and echocardiographic response rate was 69.8% during 6 month follow-up. The echocardiographic response rate for patients with atrial fibrillation was lower than that for patients with sinus rhythm (45.5% vs. 76.2%, P < 0.05). In patients with sinus rhythm, higher response rate was seen in patients with widen QRS duration, lower pulmonary systolic pressure and prolonged left ventricular pre-ejection time (LVPT) while response rate was not affected by LVEF, left ventricular volume, NYHA functional class and intra-ventricular dyssynchrony. CONCLUSIONS: Response rate to CRT was lower in patients with atrial fibrillation compared to patients with sinus rhythm. In patients with sinus rhythm, QRS duration, LVPT and pulmonary systolic pressure were useful parameters to predict the response to CRT.

[Comparison of different pacing sites of the right ventricle on left ventricular mechanical synchrony and systolic performance using tissue Doppler imaging].

OBJECTIVE: Right ventricular apical pacing may induce cardiac desynchronize and deteriorate left ventricular systolic performance. We hypothesized that right ventricular outflow tract (RVOT) pacing could produce better mechanical synchrony and left ventricular contraction. METHODS: We enrolled nine patients without structural heart disease who underwent electrophysiological studies. The pacing sites (right apex, low septum, free wall and septum of RVOT of the right ventricle) were defined with fluoroscopy and ECG. The atrioventricular sequential pacing was applied every 5 minutes in a random order at a rate of 120 bpm. Tissue Doppler imaging was carried out with GE VIVID 7 for off-line analysis at each pacing site. The global systolic contraction amplitude (GSCA) was calculated as the average shortening amplitude of all 16 segments of left ventricle. RESULTS: The GSCA during pacing was 5.76 mm +/- 0.66 mm at free wall of RVOT and 5.66 mm +/- 1.00 mm at septum of RVOT, respectively. The GSCA at both sites was significantly higher than that at apical pacing 4.82 mm +/- 0.94 mm (P < 0.05) or low septum pacing 4.82 mm +/- 1.06 mm (P < 0.05). Moreover, segmental displacement analysis showed that the longitudinal displacement of lateral, posterior, and inferior walls significantly decreased at apical pacing compared with RVOT pacing, although no difference could be demonstrated in anterior and septum walls. Accordingly, the curve of the myocardial displacement at apical or low septum pacing was M-shaped, and had a negative wave at the end of the diastole in lateral, posterior, and inferior walls. The tissue velocity during isovolumic contraction period was also higher than systolic tissue velocity in these walls. The phenomenon could seldom be seen at RVOT pacing. CONCLUSION: RVOT pacing in patients without structural heart disease is associated with more favorable immediate myocardial contraction and mechanical synchrony compared with right apical pacing or low septum pacing.

[Immediate effect of cardiac resynchronization therapy by tissue synchronization imaging and tissue tracking in patients with congestive heart failure].

OBJECTIVE: To evaluate the immediate effect of cardiac resynchronization therapy (CRT) by Doppler tissue imaging (DTI), tissue synchronization imaging (TSI) and tissue tracking imaging (TTI) in patients with congestive heart failure. METHODS: Ten patients with congestive heart failure who had cardiac resynchronization therapy were enrolled. The TSI and TTI imaging were performed by GE vivid 7 with M3s probe. The TTI image was obtained in diastole to determine delayed longitude contraction (DLC). The left ventricular ejection fraction (LVEF), the percentage of delayed longitude contraction segments (DLC), the standard deviation of the time to peak myocardial systolic contraction of 16 segments (Ts-SD), the standard deviation of the time to peak myocardial diastole of 16 segments (Td-SD), the systolic velocity of right ventricule (RV-Sm) and the average systolic velocity of mitral valve annulus (LV-Sm) were measured. The intraventricular dyssynchrony could be semi-quantified by TSI as 4 (red), 3 (orange), 2 (yellow), 1 (green), and the average value of 16 segments was defined as the TSI index. The immediate changes of these parameters were investigated when the pacemaker was turned on and off. The correlation of the Ts and TSI index was also analyzed. RESULTS: When the pacemaker was on, the LVEF improved significantly from (37 +/- 11.30)% to (46 +/- 10.10)% (P < 0.01), and LV-Sm increased significantly from (3.16 +/- 0.87) cm/s to (3.76 +/- 0.74) cm/s (P < 0.01), RV-Sm increased significantly from (6.79 +/- 1.78) cm/s to (7.75 +/- 1.92) cm/s (P < 0.01). DLCs decreased significantly from (35 +/- 6.04)% to (18.13 +/- 9.97)% (P < 0.01), Ts-SD decreased from (83.97 +/- 33.02) ms to (52.67 +/- 19.65) ms, P < 0.05, Td-SD decreased from (87.81 +/- 22.34) ms to (63.45 +/- 31.49) ms, P < 0.05 and TSI index reduced from 2.11 +/- 0.15 to 1.60 +/- 0.33 (P < 0.01) respectively. In addition, the reduction of TSI index correlated significantly with that of Ts-SD (r = 0.75, P < 0.05). CONCLUSIONS: CRT could immediately improve the systolic and diastolic synchrony of the left ventricle and ventricular function. TSI and TTI may be as the new effective modalities to assess the mechanical dyssynchrony. TSI index was direct and reliable in this study.

Pro-apoptotic role of nuclear factor-κB in adriamycin-induced acute myocardial injury in rats.

Nuclear factor κB (NF-κB) is activated by a wide range of inducers and is able to mediate gene transcription. We investigated the role of NF-κB in adriamycin-induced myocardial injury in rats and its mechanism of action. A total of 30 male Wistar rats were randomly divided into 3 groups: control, anthracycline antibiotic adriamycin (ADR) and ADR + pyrrolidine dithiocarbamate (PDTC). Myocardial apoptosis was detected by TUNEL assay; myocardium p53 gene expression was examined by RT-PCR analysis; location and distribution of p53 was observed by immunohistochemical assay; myocardial expression of p53 protein was assessed by Western blot analysis and activity of NF-κB was evaluated by electrophoretic mobility shift assay. The binding activity of NF-κB, myocardial apoptotic index and expression of p53 increased significantly in the ADR groups. All of these changes induced by ADR were inhibited by PDTC. It was concluded that NF-κB activation may be pro-apoptotic through regulation of the expression of p53 in adriamycin-induced myocardial injury.

Longitudinal two-dimensional strain rate imaging: a potential approach to predict the response to cardiac resynchronization therapy.

The purpose of our study was to test the usefulness of speckle-tracking two-dimensional echocardiography (in particular longitudinal strain and strain rate) in predicting the response to cardiac resynchronization therapy. The standard approach has been tissue Doppler-based echocardiographic imaging (TDI) has initially showed promising results in small clinical trials. However, recent larger, prospective randomized clinical trials (PROSPECT, ReTHINK) showed that TDI is inadequate to predict response from CRT in patients with heart failure. Altogether, these data suggest the need to identify alternative echocardiographic parameters to predict the response to CRT. We included 53 patients suffering from heart failure, who received CRT. TDI and two-dimensional speckle tracking imaging in addition to standard echocardiography were performed prior to CRT. The standard deviation of time to peak longitudinal strain in 12 LV segments (Tstrain-SD) and the standard deviation of time to the end of longitudinal systolic strain rate in six basal LV segments (Tsr-SD) were calculated. Standard echocardiography was performed 6 months after CRT. Patients were classified as echocardiographic responders if the LV end-systolic volume was reduced >15% compared with baseline volumes. No significant difference was seen in baseline Ts-SD, and Tstrain-SD between non-responders and responders. However, the Tsr-SD was much higher in responders than non-responders (95.9 +/- 33.0% vs. 64.8 +/- 39.6%, P < 0.05), and it showed a sensitivity of 73% and specificity of 65% for the defined echocardiographic response using a cutoff value of 70.7 ms. Our study demonstrates that longitudinal two-dimensional strain rate imaging is a promising potential echocardiographic parameter to predict benefit from CRT in patients with heart failure. This hypothesis needs to be further tested in prospective randomized clinical trials.