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.

     

Idiopathic hyperzincemia with associated copper deficiency anemia: a diagnostic dilemma

Prompt serum copper and zinc in addition to vitamin B12 levels should be measured in patients suffering from refractory anemia with neurological symptoms. A timely copper supplementation can help revert the hematological and possibly the neurological manifestations.     

Emergence of <Emphasis Type="Italic">Moraxella bovoculi</Emphasis> Associated with Keratoconjunctivitis in an Organized Dairy Farm of India

An investigation was carried out in an organized dairy farm of Tamil Nadu State, India where cattle were reported to have eye infection. Preliminary clinical intervention revealed that the animals had infectious bovine keratoconjunctivitis (IBK). Isolation and identification of pathogen from eye swab revealed the presence of Moraxella spp. On further molecular characterization by Polymerase chain reaction (PCR) suggested that the isolate as Moraxella bovoculi. PCR followed by sequencing was carried and the results showed that the isolate was M. bovoculi and the sequence was submitted in the GenBank with the sequence id. KX121047. Animals were treated with antibiotics as per the results from antibiotic sensitivity test and treatment yielded good results as the animals responded to treatment. This report is the first of its kind from India as there was no previous report regarding M. bovoculi from the country. Further insights into the bacterial genome can aid in identification of the genes or regions involved in pathogenesis of IBK and also to carve out the prevention and control strategies of IBK.     

3T multiparametric MR imaging,PIRADSv2-based detection of index prostate cancer lesions in the transition zone and the peripheral zone using whole mount histopathology as reference standard

Abdominal Radiology - To evaluate 3T mpMRI characteristics of transition zone and peripheral zone index prostate cancer lesions stratified by Gleason Score and PI-RADSv2 with whole mount...     

Macular thickness measurements using Copernicus Spectral Domain Optical Coherence Tomography

Purpose

To provide normal macular thickness measurements using Spectral Domain Optical Coherence Tomography (SDOCT, Copernicus, Optopol Technologies, Zawierci, Poland).

Methods

Fifty-eight eyes of 58 healthy subjects were included in this prospective study. All subjects had comprehensive ophthalmic examination including best-corrected visual acuity (BCVA). All the subjects underwent Copernicus SDOCT. Central foveal thickness (CFT) and photoreceptor layer (PRL) thickness were measured and expressed as mean and standard deviation. Mean retinal thickness for each of the 9 regions defined in the Early Treatment Diabetic Retinopathy Study was reported. The data were compared with published literature in Indians using Stratus and Spectralis OCTs to assess variation in instrument measurements.

Results

The mean CFT in the study sample was 173.8 ± 18.16 microns (131–215 microns) and the mean PRL thickness was 65.48 ± 4.23 microns (56–74 microns). No significant difference (p = 0.148) was found between CFT measured automated (179.28 ± 22 microns) and manually (173.83 ± 18.1 microns). CFT was significantly lower in women (167.62 ± 16.36 microns) compared to men (180.03 ± 18 microns) (p = 0.008). Mean retinal thickness reported in this study was significantly different from published literature using Stratus OCT and Spectralis OCT.

Conclusion

We report the normal mean retinal thickness in central 1 mm area to be between 138 and 242 microns in Indian population using Copernicus SDOCT. We suggest that different OCT instruments cannot be used interchangeably for the measurement of macular thickness as they vary in segmentation algorithms.     

Human hepatocyte assessment of imatinib drug–drug interactions – complexities in clinical translation

Aim

Inducers and inhibitors of CYP3A, such as ritonavir and efavirenz, may be used as part of the highly active antiretroviral therapy (HAART) to treat HIV patients. HIV patients with chronic myeloid leukemia or gastrointestinal stromal tumour may need imatinib, a CYP3A4 substrate with known exposure response–relationships. Administration of imatinib to patients on ritonavir or efavirenz may result in altered imatinib exposure leading to increased toxicity or failure of therapy, respectively. We used primary human hepatocyte cultures to evaluate the magnitude of interaction between imatinib and ritonavir/efavirenz.

Methods

Hepatocytes were pre-treated with vehicle, ritonavir, ketoconazole, efavirenz or rifampicin, and the metabolism of imatinib was characterized over time. Concentrations of imatinib and metabolite were quantitated in combined lysate and medium, using LC-MS.

Results

The predicted changes in imatinib CL_oral (95% CI) with ketoconazole, ritonavir, rifampicin and efavirenz were 4.0-fold (0, 9.2) lower, 2.8-fold (0.04, 5.5) lower, 2.9-fold (2.2, 3.5) higher and 2.0-fold (0.42, 3.5) higher, respectively. These predictions were in good agreement with clinical single dose drug–drug interaction studies, but not with reports of imatinib interactions at steady-state. Alterations in metabolism were similar after acute or chronic imatinib exposure.

Conclusions

In vitro human hepatocytes predicted increased clearance of imatinib with inducers and decreased clearance with inhibitors of CYP enzymes. The impact of HAART on imatinib may depend on whether it is being initiated or has already been dosed chronically in patients. Therapeutic drug monitoring may have a role in optimizing imatinib therapy in this patient population.