Myo-inositol hexakisphosphate (IP6) is a natural product known to inhibit vascular calcification (VC), but with limited potency and low plasma exposure following bolus administration. Here we report ...the design of a series of inositol phosphate analogs as crystallization inhibitors, among which 4,6-di-O-(methoxy-diethyleneglycol)-myo-inositol-1,2,3,5-tetrakis(phosphate), (OEG
)
-IP4, displays increased in vitro activity, as well as more favorable pharmacokinetic and safety profiles than IP6 after subcutaneous injection. (OEG
)
-IP4 potently stabilizes calciprotein particle (CPP) growth, consistently demonstrates low micromolar activity in different in vitro models of VC (i.e., human serum, primary cell cultures, and tissue explants), and largely abolishes the development of VC in rodent models, while not causing toxicity related to serum calcium chelation. The data suggest a mechanism of action independent of the etiology of VC, whereby (OEG
)
-IP4 disrupts the nucleation and growth of pathological calcification.
CT coronary artery calcium scoring (CACS) is additive to traditional risk factors for predicting future cardiac events but is associated with relatively high radiation doses. We assessed the ...feasibility of CACS radiation dose reduction using a lower tube current and iterative reconstruction (IR).
Artificial noise was added to the raw data from 27 CACS studies from patients who were symptomatic to simulate lower tube current scanning (75, 50 and 25% original current). All studies were performed on the same CT scanner at 120 kVp. Data were reconstructed using filtered back projection Quantum Denoising Software (QDS+) and IR adaptive iterative dose reduction three dimensional mild, standard and strong. Agatston scores were independently measured by two readers. CACS percentile risk scores were calculated.
At 75, 50 and 25% tube currents, all adaptive iterative dose reduction (AIDR) reconstructions decreased image noise relative to QDS+ (p < 0.05). All AIDR reconstructions resulted in small reductions in Agatston score relative to QDS+ at the standard tube current (p < 0.05). Agatston scores increased with QDS+ at 75, 50 and 25% tube current (p < 0.05), whereas no significant change was observed with AIDR mild at any tested tube current. No difference in the percentile risk score with AIDR mild at any tube current occurred compared with QDS+ at standard tube current (p > 0.05). Interobserver agreement for AIDR mild remained excellent even at 25% tube current (intraclass correlation coefficient 0.997).
Up to 75% reduction in CACS tube current is feasible using AIDR mild.
AIDR mild IR permits low tube current CACS whilst maintaining excellent intraobserver and interobserver variability and without altering risk classification.
We investigated whether motion correction of gated
F-fluoride PET/CT and PET/MRI of the aortic valve could improve PET quantitation and image quality.
A diffeomorphic, mass-preserving, anatomy-guided ...registration algorithm was used to align the PET images from 4 cardiac gates, preserving all counts, and apply them to the PET/MRI and PET/CT data of 6 patients with aortic stenosis. Measured signal-to-noise ratios (SNRs) and target-to-background ratios (TBRs) were compared with the standard method of using only the diastolic gate.
High-intensity aortic valve
F-fluoride uptake was observed in all patients. After motion correction, SNR and TBR increased compared with the median diastolic gate (SNR, 51.61 vs. 21.0; TBR, 2.85 vs. 2.22) and the median summed data (SNR, 51.61 vs. 34.10; TBR, 2.85 vs. 1.95) (
= 0.028 for all). Furthermore, noise decreased from 0.105 (median, diastolic) to 0.042 (median, motion-corrected) (
= 0.028).
Motion correction of hybrid
F-fluoride PET markedly improves SNR, resulting in improved image quality.
Aims
This study examined the effect of experimentally‐induced hypoglycaemia on measures of myocardial blood flow and myocardial injury in adults with, and without, type 1 diabetes.
Methods
In a ...prospective, randomised, open‐label, blinded, endpoint cross‐over study, 17 young adults with type 1 diabetes with no cardiovascular risk factors, and 10 healthy non‐diabetic volunteers, underwent hyperinsulinaemic‐euglycaemic (blood glucose 4.5–5.5 mmol/L) and hypoglycaemic (2.2–2.5 mmol/L) clamps. Myocardial blood flow was assessed using transthoracic echocardiography Doppler coronary flow reserve (CFR) and myocardial injury using plasma high‐sensitivity cardiac troponin I (hs‐cTnI) concentration.
Results
During hypoglycaemia, coronary flow reserve trended non‐significantly lower in those with type 1 diabetes than in the non‐diabetic participants (3.54 ± 0.47 vs. 3.89 ± 0.89). A generalised linear mixed‐model analysis examined diabetes status and euglycaemia or hypoglycaemia as factors affecting CFR. No statistically significant difference in CFR was observed for diabetes status (p = .23) or between euglycaemia and hypoglycaemia (p = .31). No changes in hs‐cTnI occurred during hypoglycaemia or in the recovery period (p = .86).
Conclusions
A small change in CFR was not statistically significant in this study, implying hypoglycaemia may require more than coronary vasomotor dysfunction to cause harm. Further larger studies are required to investigate this putative problem.
Hypoglycaemia may require more than coronary vasomotor dysfunction to mediate harm
Balloon aortic valvuloplasty (BAV) remains a treatment option for the selected patients with severe aortic stenosis. We examined clinical outcomes and predictors of prognosis in patients undergoing ...BAV for severe aortic stenosis.
We identified all patients undergoing BAV from January 2010 to March 2018 (n=167) at a single transcatheter aortic valve implantation (TAVI) centre. Patient demographics, investigations, subsequent interventions and clinical outcomes were obtained from electronic health records.
Patients undergoing BAV were elderly (median age 80, IQR 73-86 years) and half (n=87, 52%) were male. All-cause mortality at 30 days and 12 months was 11% and 43%, respectively. Reduce ejection fraction (EF 30%-50%: HR 1.76, 95% CI 1.05 to 2.94; EF <30%: HR 1.90, 95% CI 1.12 to 3.20) was the only independent predictor at baseline of overall mortality. Median survival was 212 (IQR 54-490) days from the index procedure. Mortality at 1 year was lowest in patients who subsequently underwent TAVI or SAVR but high among those who had no further interventions or those who had a repeat BAV (14%, 19%, 60%, 89% respectively, log-rank p<0.001).
BAV as a bridge to definitive aortic valve intervention in carefully selected patients offers acceptable outcomes. These contemporary observational findings demonstrate the ongoing potential utility of BAV in the TAVI era.
Background: Exposure to fine particulate air pollution is associated with increased cardiovascular morbidity and mortality. We previously demonstrated that exposure to dilute diesel exhaust causes ...vascular dysfunction in humans. Objectives: We conducted a study to determine whether exposure to ambient particulate matter causes vascular dysfunction. Methods: Twelve male patients with stable coronary heart disease and 12 age-matched volunteers were exposed to concentrated ambient fine and ultrafine particles (CAPs) or filtered air for 2 hr using a randomized, double-blind cross-over study design. We measured peripheral vascular vasomotor and fibrinolytic function, and inflammatory variables-including circulating leukocytes, serum C-reactive protein, and exhaled breath 8-isoprostane and nitrotyrosine-6-8 hr after both exposures. Results: Particulate concentrations (mean ± SE) in the exposure chamber $(190\pm 37\ \mu {\rm g}/{\rm m}^{3})$ were higher than ambient levels $(31\pm 8\ \mu {\rm g}/{\rm m}^{3})$ and levels in filtered air $(0.5\pm 0.4\ \mu {\rm g}/{\rm m}^{3};p<0.001)$. Chemical analysis of CAPs identified low levels of elemental carbon. Exhaled breath 8-isoprostane concentrations increased after exposure to CAPs (16.9 ± 8.5 vs. 4.9 ± 1.2 pg/mL, p < 0.05), but markers of systemic inflammation were largely unchanged. Although there was a dose-dependent increase in blood flow and plasma tissue plasminogen activator release (p < 0.001 for all), CAPs exposure had no effect on vascular function in either group. Conclusions: Despite achieving marked increases in particulate matter, exposure to CAPs-low in combustion-derived particles-did not affect vasomotor or fibrinolytic function in either middle-aged healthy volunteers or patients with coronary heart disease. These findings contrast with previous exposures to dilute diesel exhaust and highlight the importance of particle composition in determining the vascular effects of particulate matter in humans.
Inflammation detected through the uptake of ultrasmall superparamagnetic particles of iron oxide (USPIO) on magnetic resonance imaging (MRI) and finite element (FE) modelling of tissue stress both ...hold potential in the assessment of abdominal aortic aneurysm (AAA) rupture risk. This study aimed to examine the spatial relationship between these two biomarkers. Patients (
n
= 50) > 40 years with AAA maximum diameters > = 40 mm underwent USPIO-enhanced MRI and computed tomography angiogram (CTA). USPIO uptake was compared with wall stress predictions from CTA-based patient-specific FE models of each aneurysm. Elevated stress was commonly observed in areas vulnerable to rupture (e.g. posterior wall and shoulder). Only 16% of aneurysms exhibited co-localisation of elevated stress and mural USPIO enhancement. Globally, no correlation was observed between stress and other measures of USPIO uptake (i.e. mean or peak). It is suggested that cellular inflammation and stress may represent different but complimentary aspects of AAA disease progression.
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