To evaluate the effect of linagliptin on left ventricular systolic function beyond glycaemic control in type 2 diabetes mellitus.
A multicentre, randomised, double-blind, placebo controlled, ...parallel-group study, was performed (the DYDA 2 trial). Individuals with type 2 diabetes mellitus and asymptomatic impaired left ventricular systolic function were randomly allocated in a 1:1 ratio to receive for 48 weeks either linagliptin 5 mg daily or placebo, in addition to their diabetes therapy. Eligibility criteria were age 40 years and older, haemoglobin A1c 8.0% or less (≤64 mmol/mol), no history of cardiac disease, concentric left ventricular geometry (relative wall thickness ≥0.42), impaired left ventricular systolic function defined as midwall fractional shortening 15% or less at baseline echocardiography. The primary end point was the modification of midwall fractional shortening over time. The main secondary objectives were changes in diastolic and/or in longitudinal left ventricular systolic function as measured by tissue Doppler echocardiography. One hundred and eighty-eight patients were enrolled, predominantly men with typical insulin-resistance comorbidities. At baseline, mean midwall fractional shortening was 13.3%±2.5. At final evaluation, 88 linagliptin patients and 86 placebo patients were compared: midwall fractional shortening increased from 13.29 to 13.82 (+4.1%) in the linagliptin group, from 13.58 to 13.84 in the placebo group (+1.8%, analysis of covariance P = 0.86), corresponding to a 2.3-fold higher increase in linagliptin than the placebo group, although non-statistically significant. Also, changes in diastolic and longitudinal left ventricular systolic function did not differ between the groups. Serious adverse events or linagliptin/placebo permanent discontinuation occurred in very few cases and in the same percentage between the groups.
In the DYDA 2 patients the addition of linagliptin to stable diabetes therapy was safe and provided a modest non-significant increase in left ventricular systolic function measured as midwall fractional shortening.
ClinicalTrial.gov (ID NCT02851745).
Background: Individuals with diabetes mellitus (DM) have a higher risk to develop heart failure. Clinical guidelines emphasize the importance of early diagnosis of left ventricular dysfunction (LVD) ...and preventive interventions in these patients. In this study we assessed the prevalence of LVD, systolic or diastolic, in DM patients without known cardiac disease recruited in the ‘left ventricular DYsfunction in DiAbetes (DYDA)’ study.
Design and methods: We performed clinical, ECG, laboratory, and echocardiographic exams in 960 patients (61 ± 8 years, 59% hypertensive) recruited in the DYDA study from 37 Italian diabetes referral centres. ECG and echo exams were read in central facilities. Systolic LVD was defined as ejection fraction ≤50% or midwall shortening (MFS) ≤15%. Diastolic LVD was identified when transmitral E/A was out of the range of 0.75–1.5 or deceleration time of mitral E wave ≤140 msec.
Results: Echocardiographic data were obtained in 751 patients (78.2%). Isolated systolic LVD was detected in 22.0% of patients, isolated diastolic LVD in 21.5%, and combined systolic and diastolic LVD in 12.7%. All patients with systolic LVD had MFS ≤15%, while only 9% had an ejection fraction ≤50%. Higher LV mass, relative wall thickness, prevalence of concentric geometry, and LV hypertrophy characterized the patients with LVD.
Conclusions: LVD is present in more than half of DM patients without clinically detectable cardiac disease and is associated with LV hypertrophy and concentric LV geometry. One-third of patients exhibits systolic LVD detectable at the midwall level.
BACKGROUNDAn inappropriately high left ventricular mass (iLVM) may be detected in patients with diabetes mellitus. Several hemodynamic and nonhemodynamic factors stimulating LVM growth may actively ...operate in these patients. In this study, we assessed prevalence and factors associated with iLVM in patients with diabetes mellitus.
METHODSWe analyzed baseline data from 708 patients (61 ± 7 years, 57% treated for hypertension) with type 2 diabetes mellitus without evidence of cardiac disease enrolled in the left ventricular dysfunction in diabetes study. iLVM was diagnosed by Doppler echocardiography as LVM more than 28% of the expected LVM predicted from height, sex and stroke work.
RESULTSiLVM was detected in 166 patients (23%), irrespective of concomitant hypertension. Patients with iLVM were more frequently women, had higher BMI and prevalence of metabolic syndrome, higher serum triglyceride levels and were treated more frequently with metformin and diuretics. In a multivariate model, female sex odds ratio (OR) 1.502 (95% confidence interval (CI) 1.010–2.231), P = 0.04, higher serum triglyceride levels OR 1.007 (95% CI 1.003–1.012), P < 0.001 and BMI OR 1.220 (95% CI 1.116–1.335), P < 0.001 emerged independently related to iLVM.
CONCLUSIONiLVM is detectable in about a quarter of patients with type 2 diabetes mellitus without evidence of cardiac disease and is unrelated to blood pressure levels. The association between LVM and some components of metabolic syndrome in these patients may have important practical implications.
Purpose
A multicentre, randomized, double-blind, placebo-controlled, parallel-group study aimed to define the potential positive effect of dipeptidyl peptidase-4 inhibition on left ventricular ...systolic function (LVSF) beyond glycemic control in type 2 diabetes mellitus (T2DM) (DYDA 2™ trial).
Methods
Individuals with fairly controlled T2DM and asymptomatic impaired LVSF were randomized in a 1:1 ratio to receive for 48 weeks either linagliptin 5 mg daily or placebo, in addition to their stable diabetes therapy. Eligibility criteria were age ≥ 40 years, history of T2DM with a duration of at least 6 months, HbA1c ≤ 8.0% (≤ 64 mmol/mol), no history or clinical signs/symptoms of cardiac disease, evidence at baseline echocardiography of concentric LV geometry (relative wall thickness ≥ 0.42), and impaired LVSF defined as midwall fractional shortening (MFS) ≤ 15%. The primary end-point was the modification from baseline to 48 weeks of MFS. As an exploratory analysis, significant changes in LV global longitudinal strain and global circumferential strain, measured by speckle tracking echocardiography, were also considered. Secondary objectives were changes in diastolic and/or in systolic longitudinal function as measured by tissue Doppler.
Results
A total of 188 patients were enrolled. They were predominantly males, mildly obese, with typical insulin-resistance co-morbidities such as hypertension and dyslipidemia. Mean relative wall thickness was 0.51 ± 0.09 and mean MFS 13.3% ± 2.5.
Conclusions
DYDA 2 is the first randomized, double-blind, placebo-controlled trial to explore the effect of a dipeptidyl peptidase-4 inhibitor on LVSF in T2DM patients in primary prevention regardless of glycemic control. The main characteristics of the enrolled population are reported.
Trial registration
ClinicalTrial.gov
Identifier: NCT02851745.
•A Godunov-type MHD code using an entropy-conserving HLLD solver has been developed.•The entropy-conserving HLLD solver performs well for many astrophysical problems.•Tests of the ideal MHD, ...viscosity and diffusivity modules are shown.•Applications of the code to various astrophysical problems are shown.
We describe a Godunov-type magnetohydrodynamic (MHD) code based on the Miyoshi and Kusano (2005) solver which can be used to solve various astrophysical hydrodynamic and MHD problems. The energy equation is in the form of entropy conservation. The code has been implemented on several different coordinate systems: 2.5D axisymmetric cylindrical coordinates, 2D Cartesian coordinates, 2D plane polar coordinates, and fully 3D cylindrical coordinates. Viscosity and diffusivity are implemented in the code to control the accretion rate in the disk and the rate of penetration of the disk matter through the magnetic field lines. The code has been utilized for the numerical investigations of a number of different astrophysical problems, several examples of which are shown.
Background: Better knowledge of prevalence and early-stage determinants of subclinical left ventricular dysfunction (LVD) in type 2 diabetes would be useful to design prevention strategies. The ...objective of the LVD in Diabetes (DYDA) study was to assess these points in patients without established cardiac disease.
Method: Baseline clinical, ECG, laboratory and echocardiographic data from 751 patients (61 ± 7 years, 59% hypertensive) recruited by 37 Italian diabetes clinics were analysed. Clinical history, life habits, laboratory data (NT-proBNP, HsCRP, HbA1c, serum glucose, lipids and creatinine, liver enzymes, microalbuminuria, glomerular filtrate) and data on microvascular complications and drug therapy were collected.
Results: LVD was present in 59.9% of patients. Age (OR 1.05, 95% CI 1.02–1.07), HbA1c (OR 1.27, 95% CI 1.09–1.49), triglycerides (OR 1.003, 95% CI 1.001–1.006), treatment with metformin (OR 1.62, 95% CI 1.09–2.40) and doxazosine (OR 2.48, 95% CI 1.10–5.55) were independent predictors of LVD. Glitazones were associated with reduced risk of diastolic dysfunction (OR 0.44, 95% CI 0.22–0.87) whereas waist circumference and metformin were adversely associated with systolic dysfunction (OR 1.02, 95% CI 1.01–1.04 and 1.57, 95% CI 1.01–2.43, respectively).
Conclusion: In asymptomatic and fairly controlled diabetic patients, age, worse HbA1c, traits of insulin resistance, such as visceral adiposity and triglycerides or treatment with metformin, and use of doxazosin indicate greater risk of LVD. Glitazones, at this stage, seem to be associated with better diastolic performance.
To assess the potential risk factors for pneumothorax secondary to pulmonary radiofrequency (RF) ablation.
Six electronic databases were searched from inception to February 2014 for studies assessing ...potential patient-related, tumor-related, or treatment-related risk factors for pneumothorax during pulmonary RF ablation. Study selection, data collection, and quality assessment were done by three independent reviewers.
Among 771 studies identified in the search, 10 retrospective cohort studies met inclusion criteria. There were 981 patients (61.5% male) with a mean age of 64.2 years included (259 primary lung tumors, 722 metastatic tumors). The prevalence of pneumothorax was 37% (95% confidence interval CI, 29%-46%) in 1,916 RF ablation sessions. The potential patient-related and tumor-related risk factors for pneumothorax were increased age (mean difference MD, 2.09; 95% CI 0.11-4.06; I(2) = 0%), male gender (unadjusted odds ratio OR, 2.20; 95% CI 1.49-3.27; I(2) = 0%), no history of lung surgery (unadjusted OR, 0.29; 95% CI 0.19-0.44; I(2) = 0%), and a greater number of tumors ablated (MD, 0.50; 95% CI 0.27-0.73; I(2) = 0%).
Based on available observational studies, the results suggest risk factors for pneumothorax secondary to pulmonary RF ablation may include increased age, male gender, no history of lung surgery, number of tumors ablated, and increased length of the aerated lung traversed by the electrode. The findings from this systematic review should be interpreted with caution because of the inherent limitations of the retrospective observational design.
The accretion of matter onto black holes and neutron stars often leads to the launching of outflows that can greatly affect the environments surrounding the compact object. In supermassive black ...holes, these outflows can even be powerful enough to dictate the evolution of the entire host galaxy, and yet, to date, we do not understand how these so-called accretion disk winds are launched - whether by radiation pressure, magnetic forces, thermal irradiation, or a combination thereof. An important means of studying disk winds produced near the central compact object is through X-ray absorption line spectroscopy, which allows us to probe outflow properties along a single line of sight, but usually provides little information about the global 3D disk wind structure that is vital for understanding the launching mechanism and total wind energy budget. Here, we study Hercules X-1, a unique, nearly edge-on X-ray binary with a warped accretion disk precessing with a period of about 35 days. This disk precession results in changing sightlines towards the neutron star, through the ionized outflow. We perform time-resolved X-ray spectroscopy over the precession phase and detect a strong decrease in the wind column density by three orders of magnitude as our sightline progressively samples the wind at greater heights above the accretion disk. The wind becomes clumpier as it rises upwards and expands away from the neutron star. Modelling the warped disk shape, we create a 2D map of wind properties. This unique measurement of the vertical structure of an accretion disk wind allows direct comparisons to 3D global simulations to reveal the outflow launching mechanism.
Hercules X-1 is a nearly edge-on accreting X-ray pulsar with a warped accretion disk, precessing with a period of about 35 days. The disk precession allows for unique and changing sightlines towards ...the X-ray source. To investigate the accretion flow at a variety of sightlines, we obtained a large observational campaign on Her X-1 with XMM-Newton (380 ks exposure) and Chandra (50 ks exposure) for a significant fraction of a single disk precession cycle, resulting in one of the best datasets taken to date on a neutron star X-ray binary. Here we present the spectral analysis of the High State high-resolution grating and CCD datasets, including the extensive archival data available for this famous system. The observations reveal a complex Fe K region structure, with three emission line components of different velocity widths. Similarly, the high-resolution soft X-ray spectra reveal a number of emission lines of various widths. We correct for the uncertain gain of the EPIC-pn Timing mode spectra, and track the evolution of these spectral components with Her X-1 precession phase and observed luminosity. We find evidence for three groups of emission lines: one originates in the outer accretion disk (10^5 RG from the neutron star). The second line group plausibly originates at the boundary between the inner disk and the pulsar magnetosphere (10^3 RG). The last group is too broad to arise in the magnetically-truncated disk and instead must originate very close to the neutron star surface, likely from X-ray reflection from the accretion curtain (~10^2 RG).
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