Right ventricular dysfunction is a predictor of non-response and clinical outcome following cardiac resynchronization therapy

Background

Cardiac resynchronization therapy (CRT) is an established treatment in advanced heart failure (HF). However, an important subset does not derive a significant benefit. Despite an established predictive role in HF, the significance of right ventricular (RV) dysfunction in predicting clinical benefit from CRT remains unclear. We investigated the role of RV function, assessed by cardiovascular magnetic resonance (CMR), in predicting response to and major adverse clinical events in HF patients undergoing CRT.

Methods

Sixty consecutive patients were evaluated with CMR prior to CRT implantation in a tertiary cardiac centre. The primary end-point was a composite of death from any cause or unplanned hospitalization for a major cardiovascular event. The secondary end-point was response to therapy, defined as improvement in left ventricular ejection fraction ≥ 5% on echocardiography at one year.

Results

Eighteen patients (30%) met the primary end-point over a median follow-up period of 26 months, and 27 out of 56 patients (48%) were considered responders to CRT. On time-to-event analysis, only atrial fibrillation (HR 2.6, 95% CI 1.02-6.84, p = 0.047) and RV dysfunction, either by a reduced right ventricular ejection fraction-RVEF (HR 0.96, 95% CI 0.94-0.99, p = 0.006) or tricuspid annular plane systolic excursion-TAPSE (HR 0.88, 95% CI, 0.80-0.96, p = 0.006), were significant predictors of adverse events. On logistic regression analysis, preserved RVEF (OR 1.05, 95% CI 1.01-1.09, p = 0.01) and myocardial scar burden (OR 0.90, 95% CI 0.83-0.96, p = 0.004) were the sole independent predictors of response to CRT. Patients with marked RV dysfunction (RVEF < 30%) had a particularly low response rate (18.2%) to CRT.

Conclusions

Right ventricular function is an important predictor of both response to CRT and long-term clinical outcome. Routine assessment of the right ventricle should be considered in the evaluation of patients for CRT.     

Cardiovascular magnetic resonance tagging of the right ventricular free wall for the assessment of long axis myocardial function in congenital heart disease

Background

Right ventricular ejection fraction (RV-EF) has traditionally been used to measure and compare RV function serially over time, but may be a relatively insensitive marker of change in RV myocardial contractile function. We developed a cardiovascular magnetic resonance (CMR) tagging-based technique with a view to rapid and reproducible measurement of RV long axis function and applied it in patients with congenital heart disease.

Methods

We studied 84 patients: 56 with repaired Tetralogy of Fallot (rTOF); 28 with atrial septal defect (ASD): 13 with and 15 without pulmonary hypertension (RV pressure > 40 mmHG by echocardiography). For comparison, 20 healthy controls were studied. CMR acquisitions included an anatomically defined four chamber cine followed by a cine gradient echo-planar sequence in the same plane with a labelling pre-pulse giving a tag line across the basal myocardium. RV tag displacement was measured with automated registration and tracking of the tag line together with standard measurement of RV-EF.

Results

Mean RV displacement was higher in the control (26 ± 3 mm) than in rTOF (16 ± 4 mm) and ASD with pulmonary hypertension (18 ± 3 mm) groups, but lower than in the ASD group without (30 ± 4 mm), P < 0.001. The technique was reproducible with inter-study bias ± 95% limits of agreement of 0.7 ± 2.7 mm. While RV-EF was lower in rTOF than in controls (49 ± 9% versus 57 ± 6%, P < 0.001), it did not differ between either ASD group and controls.

Conclusions

Measurements of RV long axis displacement by CMR tagging showed more differences between the groups studied than did RV-EF, and was reproducible, quick and easy to apply. Further work is needed to assess its potential use for the detection of longitudinal changes in RV myocardial function.     

Blood group antigens frequencies in the northeast of Iran

Background

Identification of blood group antigen frequencies in a population has various benefits in transfusion medicine. Most data in the literature include frequencies of these antigens in European and American countries. In this study for the first time we have reported frequencies of these antigens in the northeast of Iran.

Materials and methods

Blood group antigens were characterized in the 522 blood donors in Mashhad, Iran. The following antigens including ABO, Rh (D, C, E, c, e), MNSs (M, N, S, s), Lutheran (Lu^a, Lu^b), P (P, P₁), Kell (K, k, Kp^a, Kp^b), Lewis (Le^a, Le^b), Duffy (Fy^a, Fy^b) and Kidd (Jk^a, Jk^b) were typed and phenotypes frequencies were expressed as a percentage.

Results

In the ABO blood group, the most common phenotype was O (33.9%) followed by A, B and AB. In the Rh blood group, the most common antigen was e (97.9%) and R₁r (31.8%) being the most common phenotype. The most common phenotypes for MNSs, P, Lu and Kell blood group were M+N+, S−s+, P₁, Lu (a−b+), K−k+ and Kp (a−b+). A very rare phenotype of Lu (a−b−) was also observed in 2.7% of cases. We found rare phenotypes of Le (a+b+) and Fy (a−b−) in 7.9% and 3.4% of subjects, respectively.

Conclusion

We determined some differences in phenotype frequencies of blood group compared with other studies. We found higher frequencies of B blood group and also more frequencies of some rare phenotypes, Lu (a−b−), Le (a+b+) and Fy (a−b−).     

Association of annual hormonal profile with gonad maturity of mahseer (Tor tambroides) in captivity

Annual gonad hormonal profile of wild, matured mahseer (29 males and 23 female) averaging in weight between 0.95 ± 0.26 and 1.19 ± 0.23 kg for males and females, respectively, were investigated from November 2007 to November 2008 using enzyme-linked immunosorbent assay (ELISA) technique. Blood was collected from caudal vein, monthly and plasma separation by centrifugation was done to measure reproductive hormones: 17β-estradiol (E₂), testosterone (T), and 11-keto-testosterone (11KT). Gonads were sampled for histology processing to observe their maturity. Highest T level in females and males was recorded at 0.22 ± 0.016 and 0.88 ± 0.014 ng/ml, respectively. The 11KT showed several peaks and the highest value was noted at 0.7 ± 0.018 ng/ml in November 2008. The female E₂ initially was at 1.48 ± 0.16 ng/ml and significantly increased (P < 0.05) to 1.53 ± 0.39 ng/ml in November 2008. Ovaries were laden with oocytes in several stages in all the samples while testes gonad showed a high level of spermatids throughout the year. Changes in plasma level of the gonadal hormones were correlated with the ovarian and testes maturities. In conclusion, the study suggests that mahseer can be categorized as asynchronized and multiple spawner. The information gathered is important for appropriate breeding and conservation programs of the Malaysian mahseer.     

Significant association of high-risk human papillomavirus (HPV) but not of p53 polymorphisms with oral squamous cell carcinomas in Malaysia

Purpose  

The purpose of this study was to evaluate the role of HPV and p53 polymorphisms in oral squamous cell carcinomas (OSCC) affecting Malaysian population.     

Contrary effects of the receptor tyrosine kinase inhibitor vandetanib on constitutive and flow-stimulated nitric oxide elaboration in humans

Vascular endothelial growth factor regulates neoplastic angiogenesis through production of endothelium-derived NO. We performed a prospective evaluation of vascular function during treatment with vandetanib, a vascular endothelial growth receptor 2 and 3 receptor tyrosine kinase inhibitor, to determine the effects of vascular endothelial growth receptor signal interruption on endothelial function in humans. Seventeen patients with stage IV breast cancer received dose-escalated vandetanib in combination with low-dose oral chemotherapy. We measured blood pressure, systemic nitrate/nitrite levels, and brachial artery vascular function. In vitro analyses of cultured endothelial cells were performed to determine the effect of vandetanib on NO production, akt(473) phosphorylation, and endothelial NO synthase protein content and membrane localization. Vandetanib treatment for 6 weeks significantly increased blood pressure, decreased resting brachial artery diameter, and decreased plasma systemic nitrate/nitrite levels compared with baseline. Flow-mediated vasodilation was preserved, and no change was noted in nitroglycerin-mediated vasodilation. In vitro, endothelial cell nitrite levels and akt(473) phosphorylation were reduced and vascular endothelial growth receptor 2 levels did not change, but endothelial NO synthase membrane concentration doubled. Vandetanib reduces constitutive NO production and increases blood pressure, yet flow-stimulated NO bioavailability was preserved. Changes in vascular function with tyrosine kinase inhibition are complex and require further study in humans.     

Angiotensin converting enzyme DD genotype is associated with development of rheumatic heart disease in Egyptian children

Angiotensin converting enzyme (ACE) gene polymorphism was previously studied in some cardiovascular diseases. There are only few studies which investigated this polymorphism in patients with rheumatic heart disease (RHD). The results of these investigations are inconsistent. Furthermore, gene polymorphism distribution is different in various ethnic populations. We conducted this study to demonstrate this gene polymorphism in Egyptian children with RHD. Leukocytes DNA was extracted from 139 patients with RHD and 79 healthy control children. After amplification by the PCR, the products were separated by electrophoresis in 6% polyacrylamide gel and visualized after ethidium bromide staining with UV light. The PCR product is a 190-bp fragment in the absence of the insertion (D allele) and a 490-bp fragment in the presence of the insertion (I allele). Gene polymorphism was as follows: DD gene when lane contains only 190-bp fragment, II gene when lane contains only 490-bp fragment and ID gene when lane contains both fragments. We found that gene polymorphism in both control and patients groups followed the following order of distribution from highest to lowest: ID, II, DD gene. The frequency in control group was 49.4, 36.7, and 13.9%, respectively. In patients groups, the gene frequency was 42.5, 30.9, and 26.6%, respectively. DD gene frequency differs significantly between the two groups. We concluded that patients with RHD have a higher ACE-DD genotype than normal control. ACE-DD genotype may be a risk factor for RHD in Egyptian children.     

Ectopic varices in portal hypertension: computed tomographic angiography instead of repeated endoscopies for diagnosis

Ectopic varices (EcV) accounting for 1-5% of all varices in portal hypertension are composed of dilated portosystemic collaterals located in unusual sites instead of the most known gastroesophageal region. The difficulty in localization of bleeding is a great burden on the management of these patients. Herein, we present patients with EcV as well as with portal hypertension and recurrent intestinal bleeding. The sites of EcV were identified with computed tomographic angiography, after a series of inconclusive endoscopies, and moreover a selective celiac arteriographic examination of one of the patients.