The interplay between metabolic alterations,diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study

Background

Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity.

Methods

Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent ¹H-cardiovascular magnetic resonance spectroscopy (¹H-CMRS) to measure MTG (lipid/water, %), ³¹P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate.

Results

When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45?±?0.25% vs. 0.64?±?0.16%, p?=?0.009) and reduced PCr/ATP (1.60?±?0.09 vs. 2.00?±?0.10, p?=?0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO₂ max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO₂ max.

Conclusions

Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.

     

Outcome of Transurethral Plasmakinetic Vaporization for Benign Prostatic Hyperplasia

Purpose

To assess the outcome of transurethral plasmakinetic vaporization (PKVP) in the management of benign prostatic hyperplasia (BPH).

Patients and methods

From August 2010 to May 2012, 60 patients with obstructive LUTS due to BPH were included in the study. All patients were evaluated by International Prostate Symptom Score (IPSS), general examination, digital rectal examination, PSA, routine laboratory examinations, pelvi-abdominal ultrasound, trans-rectal ultrasound, and uroflowmetry. Patients with Qmax of <10 mL/sec., an IPSS of >8 and a prostate volume of >40 mL underwent transurethral PKVP.

Results

Mean age of the patients was 66.8±4.5 years. The mean times of the operation, post-operative bladder irrigation, and post-operative catheterization were 63.8±13.9 minutes, 15.2±5.7 hours, and 23.9±5.2 hours, respectively. At 3 months of follow-up, there were significant reductions in the mean IPSS from 23.4±3.5 to 9.2±3.7 (P=0.4), mean PSA from 3.03±2.2 ng/mL to 1.2±1.04 ng/mL (P value=0.02), mean post voiding residual urine from 149.8±59.5 mL to 46.9±24.1 mL (P value <0.01), and mean prostate volume from 72.8±10.3 mL to 22.7±6.1 mL (P value <0.01). Also, there was a statistically significant increase in the mean Q max. from 8.7±2.4 mL/s to 19.5±3.5 mL/s (P value <0.01).

Conclusion

PKVP is an effective and safe treatment option in the management of symptomatic BPH.     

Recombinant Human Adiponectin as a Potential Protein for Treating Diabetic Tendinopathy Promotes Tenocyte Progenitor Cells Proliferation and Tenogenic Differentiation In Vitro

Adiponectin is an adipocyte-secreting hormone that increases cell sensitivity to insulin. It has been previously demonstrated that this hormone protects against Type II Diabetes and, is found to concurrently promote cell proliferation and differentiation. It is postulated that diabetic patients who suffer from tendinopathy may benefit from using adiponectin, which not only improves the metabolism of diabetic ridden tenocytes but also promotes progenitor cell proliferation and differentiation in tendons. These changes may result in tendon regeneration, which, in diabetic tendinopathy, is difficult to treat. Considering that such findings have yet to be demonstrated, a study was thus conducted using diabetic ridden human tenocyte progenitor cells (TPC) exposed to recombinant adiponectin in vitro. TPC were isolated from tendons of diabetic patients and exposed to 10μg/ml adiponectin. Cell proliferation rate was investigated at various time points whilst qPCR were used to determine the tenogenic differentiation potential. The results showed that adiponectin significantly reduced blood glucose in animal models. The proliferation rate of adiponectin-treated TPCs was significantly higher at 6, 8 and 10 days as compared to untreated cells (p<0.05). The levels of tenogenic genes expression (collagen I, III, tenomodulin and scleraxis) were also significantly upregulated; whilst the osteogenic (Runx2), chondrogenic (Sox9) and adipogenic (PPARУγ) gene expressions remained unaltered. The results of this study suggest that adiponectin is a potential promoter that not only improves diabetic conditions, but also increases tendon progenitor cell proliferation and differentiation. These features supports the notion that adiponectin may be potentially beneficial in treating diabetic tendinopathy.     

Prevalence of cardiomyopathy in asymptomatic patients with left bundle branch block referred for cardiovascular magnetic resonance imaging

The diagnostic evaluation of patients with isolated left bundle branch block (LBBB) is challenging due to limitations of several non-invasive tests. Our aim was to evaluate the diagnostic value of cardiovascular magnetic resonance (CMR) in asymptomatic patients with LBBB. Sixty-one asymptomatic patients with complete LBBB who were referred for CMR from January 2005 to November 2010 were identified. 29 patients (18 men) had normal echocardiograms (echo) whereas 25 (18 men) had abnormal findings on echo. Six had no echo and one had poor echo windows, and these patients were excluded from further analysis. Patients with cardiac symptoms or known coronary artery disease at the time of referral were also excluded. Of the 29 patients with normal echo, 9 (31%) were found to have pathological findings on CMR. The most common abnormalities were dilated cardiomyopathy-DCM (n = 6, 21%) followed by left ventricular hypertrophy (n = 2, 7%). Of the 25 patients who had an abnormal echo, CMR confirmed the diagnosis in 19 (76%) and provided clinically relevant additional information in 13 (52%) subjects. Of these 13 patients, 9 (69%) had characteristic patterns of myocardial late gadolinium enhancement (8 mid-wall and 1 patchy distribution consistent with DCM and cardiac sarcoid, respectively). CMR detects sub-clinical cardiomyopathy in a third of asymptomatic patients with LBBB despite normal echocardiograms. In those with abnormal echocardiograms, CMR provides additional clinically relevant information in over 50% of patients, including a high prevalence of mid-wall fibrosis in patients with impaired left ventricular function. These findings support the use of CMR as a valuable adjunct to conventional investigations in asymptomatic LBBB.     

Adenosine stress native T1 mapping in severe aortic stenosis: evidence for a role of the intravascular compartment on myocardial T1 values

Background

Myocardial T1 relaxation times have been reported to be markedly abnormal in diverse myocardial pathologies, ascribed to interstitial changes, evaluated by T1 mapping and calculation of extracellular volume (ECV). T1 mapping is sensitive to myocardial water content of both intra- and extracellular in origin, but the effect of intravascular compartment changes on T1 has been largely neglected. We aimed to assess the role of intravascular compartment on native (pre-contrast) T1 values by studying the effect of adenosine-induced vasodilatation in patients with severe aortic stenosis (AS) before and after aortic valve replacement (AVR).

Methods

42 subjects (26 patients with severe AS without obstructive coronary artery disease and 16 controls) underwent cardiovascular magnetic resonance at 3 T for native T1-mapping (ShMOLLI), first-pass perfusion (myocardial perfusion reserve index-MPRI) at rest and during adenosine stress, and late gadolinium enhancement (LGE).

Results

AS patients had increased resting myocardial T1 (1196 ± 47 ms vs. 1168 ± 27 ms, p = 0.037), reduced MPRI (0.92 ± 0.31 vs. 1.74 ± 0.32, p < 0.001), and increased left ventricular mass index (LVMI) and LGE volume compared to controls. During adenosine stress, T1 in AS was similar to controls (1240 ± 51 ms vs. 1238 ± 54 ms, p = 0.88), possibly reflecting a similar level of maximal coronary vasodilatation in both groups. Conversely, the T1 response to stress was blunted in AS (ΔT1 3.7 ± 2.7% vs. 6.0 ± 4.2% in controls, p = 0.013). Seven months after AVR (n = 16) myocardial T1 and response to adenosine stress recovered towards normal. Native T1 values correlated with reduced MPRI, aortic valve area, and increased LVMI.

Conclusions

Our study suggests that native myocardial T1 values are not only influenced by interstitial and intracellular water changes, but also by changes in the intravascular compartment. Performing T1 mapping during or soon after vasodilator stress may affect ECV measurements given that hyperemia alone appears to substantially alter T1 values.     

Biological properties of bovine viral diarrhea virus quasispecies detected in the RK13 cell line

The rabbit kidney cell line RK13 has been reported to be contaminated with noncytopathogenic (ncp) bovine viral diarrhea virus (BVDV). Persistent infection was confirmed by demonstrating the stability of virus titers (10^4.6±0.5 TCID₅₀/ml) and BVDV positive cells (71.9 ± 3.12 %), over six successive passages. Based on the “exaltation of Newcastle disease virus” (END) and reverse plaque formation methods, two types of ncp viruses were isolated, END-phenomenon-positive and negative. Isolates, RK13/E⁺ and RK13/E^?, demonstrated (1) differing levels of reproducibility in cell cultures, (2) similar antigenicity against BVDV antisera, (3) identical 5′-UTR region nucleotide sequences, (4) four amino acid differences throughout the genomic open reading frame, and (5) better growth ability in primary rabbit cells than other laboratory strains when inoculated in parallel at an MOI of 0.01. Overall, the BVDV population in RK13 cells consists of at least two different END characteristic quasispecies that are adapted to cultures of rabbit origin, giving rise to naturally attenuated BVDV strains that can be used in vaccine development.     

Radioimmunoassay of salivary digoxin by simple adaptation of a kit method for serum digoxin: saliva/serum ratio and correlation

A robust commercial radioimmunoassay kit for serum digoxin was adapted to salivary assay by simple procedural modifications and shown to have satisfactory sensitivity, precision, accuracy, and specificity. The digoxin saliva/serum concentration ratio in 50 hospital patients was 0.67 +/- 0.10 (mean +/- SD), and the levels were well correlated (r = 0.96). Similar saliva/serum ratios were found in two normal subjects who took digoxin orally, and the free fraction in serum, determined by equilibrium dialysis, was found to equate with the salivary drug level. Digoxin appeared in saliva at its maximum level within 1 min of intravenous injection. Although previous studies of salivary digoxin have given widely discrepant results, the present findings are entirely consistent with the simple expectation that digoxin should appear in saliva by passive diffusion. Salivary sampling is suitable for the monitoring of digoxin therapy and pharmacokinetics, and the modified radioimmunoassay should be of value to laboratories wishing to introduce this technique.     

Immunity to hepatitis B vaccine among health care workers

The aim of this study was to determine the level of anti-HBsAg (hepatitis B surface antigen) in vaccinated high risk group. We measured anti-HBsAg concentration in blood sera of adult students aged from 19 to 37 years old. Five milliliters (5 ml) of blood sample was taken from 210 cases four months after the second dose and 126 out of 210 cases three months after the third dose of hepatitis B vaccination. All blood samples were analyzed for anti-HBsAg by ELISA method. 125 out of 210 samples (59.5%) showed anti-HBsAg concentrations higher than 20 mIu/ml and considered immune after the second dose of hepatitis B vaccination. Also, 99.2% of samples had anti-HBsAg higher than 20 mIu/ml three months after the third dose of the vaccination. Non-immune cases in males were more than females (41.2% vs.40.1%). In conclusions, our results reinforce the importance of hepatitis B vaccine in adolescents and suggest that three dose of hepatitis B vaccine is necessary to increase the seropositive rate of anti-HBsAg in adults.