The effect of left ventricular longitudinal strain on left atrial function and ventricular filling in hypertension.

AIM: To assess the relationship of global longitudinal strain during left atrial (LA) and left ventricular (LV) filling and emptying. MATERIALS AND METHODS: Using magnetic resonance imaging in 47 hypertensive patients, biplane global LV longitudinal strain was evaluated and related to LA and LV filling and emptying (by volumetric analysis), and to pulmonary vein and trans-mitral flow (by phase-contrast imaging). The results were compared to normal subjects. RESULTS: In hypertensive patients, reduced global longitudinal LV strain was associated with reduced LA reservoir (47 ± 10 versus 53 ± 9%, p<0.05), reduced LA conduit function (21 ± 9 versus 32 ± 11%, p<0.004), reduced LA early peak emptying rate (150 ± 77 versus 230 ± 88 ml/s, p=0.007), and slower early LV filling (373 ± 141 versus 478 ± 141 ml/s, p=0.03). LA peak filling rate showed a positive correlation to LV peak emptying rate (R=0.331, p=0.02). CONCLUSION: In hypertensive heart disease, impaired LV longitudinal systolic function causes reduced LA filling and emptying, and this leads directly to impaired LV filling and diastolic dysfunction.

Modifiable risk factors and the development of psoriatic arthritis in people with psoriasis.

BACKGROUND: Psoriatic arthritis (PsA) is a progressive and often destructive joint disease affecting approximately 20% of people with psoriasis. OBJECTIVES: To investigate associations between obesity, changes in body mass index (BMI), alcohol intake and smoking status and the development of PsA in people with psoriasis. METHODS: We undertook a cohort study involving incident cases of psoriasis identified from the U.K. Clinical Practice Research Datalink between 1998 and 2014. The associations between smoking, alcohol and BMI and development of PsA were assessed using generalized additive models. Additionally, the risks associated with a change in BMI during follow-up were investigated using distributed lag nonlinear models. RESULTS: We identified 90 189 incident cases of psoriasis (42% male, mean age 51 years), of whom 1409 had a subsequent record of PsA diagnosis. BMIs of 25·0-29·9, 30·0-34·9 and ≥ 35·0 kg m-2 were significantly associated with an increased risk of developing PsA compared with BMIs < 25·0 kg m-2 : adjusted odds ratios (95% confidence intervals) 1·79 (1·46-2·19), 2·10 (1·67-2·63) and 2·68 (2·09-3·43), respectively. Reducing BMI over a 10-year period (linearly) was associated with a reduction in the risk of developing PsA compared with BMI remaining constant over the same period. Increased risks of developing PsA were associated with moderate drinking but not with former or heavy drinking or with current or past smoking status. CONCLUSIONS: In this incident psoriasis cohort, increased BMI and moderate drinking, but not heavy drinking or smoking status, were associated with an increased risk of PsA in people with psoriasis. Importantly, we have shown that reducing weight may result in a reduction in the risk of developing PsA. What's already known about this topic? There is some evidence that increased body mass index is associated with an increased risk of developing psoriatic arthritis. There are conflicting results surrounding the relationship between smoking and the development of psoriatic arthritis among patients with psoriasis. What does this study add? Using a nonlinear and lagged effect of body mass index measured over time we have shown that reducing body mass index may be associated with a reduction in the risk of developing psoriatic arthritis. We have found no evidence that smoking alters the risk of developing psoriatic arthritis in patients with psoriasis.

Wave intensity analysis in the internal carotid artery of hypertensive subjects using phase-contrast MR angiography and preliminary assessment of the effect of vessel morphology on wave dynamics.

OBJECTIVE: Hypertension is associated with reduced cerebral blood flow, but it is not known how this impacts on wave dynamics or potentially relates to arterial morphology. Given the location of the internal carotid artery (ICA) and risks associated with invasive measurements, wave dynamics in this artery have not been extensively assessed in vivo. This study explores the feasibility of studying wave dynamics in the internal carotid artery non-invasively. APPROACH: Normotensive, uncontrolled and controlled hypertensive participants were recruited (daytime ambulatory blood pressure <135/85 mmHg and >135/85 mmHg, respectively; n = 38). Wave intensity, reservoir pressure and statistical shape analyses were performed on the right ICA and ascending aorta high-resolution phase-contrast magnetic resonance angiography data. MAIN RESULTS: Wave speed in the aorta was significantly lower in normotensive compared to hypertensive participants (6.7 ± 1.8 versus 11.2 ± 6.2 m s-1 for uncontrolled and 11.8 ± 4.6 m s-1 for controlled hypertensives, p = 0.02), whilst there were no differences in wave speed in the ICA. There were no significant differences between the groups for the wave intensity or reservoir pressure. Interestingly, a significant association between the anatomy of the ICA and wave energy (FCW and size, r 2 = 0.12, p = 0.04) was found. SIGNIFICANCE: This study shows it is feasible to study wave dynamics in the ICA non-invasively. Whilst changes in aortic wave speed confirmed an expected increase in arterial stiffness, this was not observed in the ICA. This might suggest a protective mechanism in the cerebral circulation, in conjunction with the effect of vessel tortuosity. Furthermore, it was observed that ICA shape correlated with wave energy but not wave speed.

Bright conjugated polymer nanoparticles containing a biodegradable shell produced at high yields and with tuneable optical properties by a scalable microfluidic device.

This study compares the performance of a microfluidic technique and a conventional bulk method to manufacture conjugated polymer nanoparticles (CPNs) embedded within a biodegradable poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG5K-PLGA55K) matrix. The influence of PEG5K-PLGA55K and conjugated polymers cyano-substituted poly(p-phenylene vinylene) (CN-PPV) and poly(9,9-dioctylfluorene-2,1,3-benzothiadiazole) (F8BT) on the physicochemical properties of the CPNs was also evaluated. Both techniques enabled CPN production with high end product yields (∼70-95%). However, while the bulk technique (solvent displacement) under optimal conditions generated small nanoparticles (∼70-100 nm) with similar optical properties (quantum yields ∼35%), the microfluidic approach produced larger CPNs (140-260 nm) with significantly superior quantum yields (49-55%) and tailored emission spectra. CPNs containing CN-PPV showed smaller size distributions and tuneable emission spectra compared to F8BT systems prepared under the same conditions. The presence of PEG5K-PLGA55K did not affect the size or optical properties of the CPNs and provided a neutral net electric charge as is often required for biomedical applications. The microfluidics flow-based device was successfully used for the continuous preparation of CPNs over a 24 hour period. On the basis of the results presented here, it can be concluded that the microfluidic device used in this study can be used to optimize the production of bright CPNs with tailored properties with good reproducibility.

Electrocardiographic detection of hypertensive left atrial enlargement in the presence of obesity: re-calibration against cardiac magnetic resonance.

Left atrial enlargement (LAE) has adverse prognostic implications in hypertension. We sought to determine the accuracy of five electrocardiogram (ECG) criteria for LAE in hypertension relative to cardiac magnetic resonance (CMR) gold standard and investigate the effect of concomitant obesity. One hundred and thirty consecutive patients (age: 51.4±15.1 years, 47% male, 51% obese, systolic blood pressure (BP): 171±29 mm Hg, diastolic BP: 97±15 mm Hg) referred for CMR (1.5 T) from a tertiary hypertension clinic were included. Patients with concomitant cardiac pathology were excluded. ECGs were assessed blindly for the following: (1) P-wave >110 ms, (2) P-mitrale, (3) P-wave axis <30°, (4) area of negative P-terminal force in V1 >40 ms.mm and (5) positive P-terminal force in augmented vector left (aVL) >0.5 mm. Left atrial volume ≥55 ml m-2, measured blindly by CMR, was defined as LAE. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy and area under the receiver operator curve were calculated. The prevalence of LAE by CMR was 26%. All the individual ECG LAE criteria were more specific than sensitive, with specificities ranging from 70% (P-axis <30o) to 99% (P-mitrale). Obesity attenuated the specificity of most of the individual ECG LAE criteria. Obesity correlated with significant lower specificity (48% vs 65%, P<0.05) and a trend towards lower sensitivity (59 vs 43%, P=0.119) when ≥1 ECG LAE criteria were present. Individual ECG criteria of LAE in hypertension are specific, but not sensitive, at identifying LAE. The ECG should not be used to excluded LAE in hypertension, particularly in obese subjects.

Quantifying sympathetic neuro-haemodynamic transduction at rest in humans: insights into sex, ageing and blood pressure control.

KEY POINTS: We have developed a simple analytical method for quantifying the transduction of sympathetic activity into vascular tone. This method demonstrates that as women age, the transfer of sympathetic nerve activity into vascular tone is increased, so that for a given level of sympathetic activity there is more vasoconstriction. In men, this measure decreases with age. Test-re-test analysis demonstrated that the new method is a reliable estimate of sympathetic transduction. We conclude that increased sympathetic vascular coupling contributes to the age-related increase in blood pressure that occurs in women only. This measure is a reliable estimate of sympathetic transduction in populations with high sympathetic nerve activity. Thus, it will provide information regarding whether treatment targeting the sympathetic nervous system, which interrupts the transfer of sympathetic nerve activity into vascular tone, will be effective in reducing blood pressure in hypertensive patients. This may provide insight into which populations will respond to certain types of anti-hypertensive medication. ABSTRACT: Sex and age differences in the sympathetic control of resting blood pressure (BP) may be due to differences in the transduction of sympathetic nerve activity (SNA) into vascular tone. Current methods for dynamically quantifying transduction focus on the relationship between SNA and vasoconstriction during a pressor stimulus, which increases BP and may be contra-indicated in patients. We describe a simple analytical method for quantifying transduction under resting conditions. We performed linear regression analysis of binned muscle SNA burst areas against diastolic BP (DBP). We assessed whether the slope of this relationship reflects the transduction of SNA into DBP. To evaluate this, we investigated whether this measure captures differences in transduction in different populations. Specifically, we (1) quantified transduction in young men (YM), young women (YW), older men (OM) and postmenopausal women (PMW); and (2) measured changes in transduction during ß-blockade using propranolol in YW, YM and PMW. YM had a greater transduction vs. OM (0.10 ± 0.01 mmHg (% s)(-1) , n = 23 vs. 0.06 ± 0.01 mmHg (% s)(-1) , n = 18; P = 0.003). Transduction was lowest in YW (0.02 ± 0.01 mmHg (% s)(-1) , n = 23) and increased during ß-blockade (0.11 ± 0.01 mmHg (% s)(-1) ; P < 0.001). Transduction in PMW (0.07 ± 0.01 mmHg (% s)(-1) , n = 23) was greater compared to YW (P = 0.001), and was not altered during ß-blockade (0.06 ± 0.01 mmHg (% s)(-1) ; P = 0.98). Importantly, transduction increased in women with age, but decreased in men. Transduction in women intersected that in men at 55 ± 1.5 years. This measure of transduction captures age- and sex-differences in the sympathetic regulation of DBP and may be valuable in quantifying transduction in disease. In particular, this measure may help target treatment strategies in specific hypertensive subpopulations.

The effect of obesity on electrocardiographic detection of hypertensive left ventricular hypertrophy: recalibration against cardiac magnetic resonance.

Electrocardiograph (ECG) criteria for left ventricular hypertrophy (LVH) are a widely used clinical tool. We recalibrated six ECG criteria for LVH against gold-standard cardiac magnetic resonance (CMR) and assessed the impact of obesity. One hundred and fifty consecutive tertiary hypertension clinic referrals for CMR (1.5 T) were reviewed. Patients with cardiac pathology potentially confounding hypertensive LVH were excluded (n=22). The final sample size was 128 (age: 51.0±15.2 years, 48% male). LVH was defined by CMR. From a 12-lead ECG, Sokolow-Lyon voltage and product, Cornell voltage and product, Gubner-Ungerleidger voltage and Romhilt-Estes score were evaluated, blinded to the CMR. ECG diagnostic performance was calculated. LVH by CMR was present in 37% and obesity in 51%. Obesity significantly reduced ECG sensitivity, because of significant attenuation in mean ECG values for Cornell voltage (22.2±5.7 vs 26.4±9.4 mm, P<0.05), Cornell product (2540±942 vs 3023±1185 mm • ms, P<0.05) and for Gubner-Ungerleider voltage (18.2±7.1 vs 23.3±1.2 mm, P<0.05). Obesity also significantly reduced ECG specificity, because of significantly higher prevalence of LV remodeling (no LVH but increased mass-to-volume ratio) in obese subjects without LVH (36% vs 16%, P<0.05), which correlated with higher mean ECG LVH criteria values. Obesity-specific partition values were generated at fixed 95% specificity; Cornell voltage had highest sensitivity in non-obese (56%) and Sokolow-Lyon product in obese patients (24%). Obesity significantly lowers ECG sensitivity at detecting LVH, by attenuating ECG LVH values, and lowers ECG specificity through changes associated with LV remodeling. Our obesity-specific ECG partition values could improve the diagnostic performance in obese patients with hypertension.

HIV-related neurocognitive impairment screening: the patient's perspective on its utility and psychological impact.

Despite ever improving advances in antiretroviral therapy, neurocognitive impairments such as asymptomatic and mild neurocognitive impairment remain a significant problem for the HIV-positive population. We distributed a post-neurocognitive impairment screening service evaluation questionnaire to assess satisfaction and anxiety. Subjects were HIV positive and aged 18-50. They were screened using the Brief Neurocognitive Score and International HIV Dementia Score as well as undergoing screening for anxiety (Generalised Anxiety Disorder Assessment [GAD-7]), depression (Participant Health Questionnaire Mood Scale [PHQ-9]) and memory (Everyday Memory Questionnaire [EMQ-R]). On completion, they were either reassured that the tests were normal or were referred for further investigation. Following assessment, subjects were asked to complete an anonymous satisfaction survey; 101 surveys were analysed. Forty-nine per cent of participants stated that they "felt better" following screening, 43% said it "made no difference", 6% stated it "worried me" and 1% "did not understand". On a scale of 0-10 of helpfulness, the mean score was 7.53. Forty-seven subjects indicated that they were referred for further investigation and 46 subjects that nothing else was needed; 8 reported they did not know. Those referred on rated satisfaction at a mean of 7.54/10 and those with normal screen as 7.09/10 (p = 0.46). Of the groups that were referred for further investigation, 6% said the test "worried them" compared to 4% in the non-referred group. Forty-nine per cent said they "felt better" despite an abnormal result compared to 50% in a normal screening result (p = 0.76). The results of this survey show that screening for neurocognitive impairment by this method is acceptable and helpful to participants. It did not lead to an increase in anxiety and there was no correlation between referred for further investigations and anxiety suggesting concerns about creating undue anxiety by screening and referral are unfounded.

The endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) predicts LV mass independent of afterload.

BACKGROUND: Nitric oxide (NO) is a modulator of left ventricular hypertrophy (LVH) and myocardial relaxation. The impact of NO availability on development of LVH has never been demonstrated in humans. We tested the hypotheses that elevation of asymmetric dimethylarginine (ADMA) concentrations (biochemical marker of decreased NO generation), and impairment of vascular responsiveness to NO donor GTN, would each predict the presence of LVH and associated LV diastolic dysfunction in a normal aging population. METHODS AND RESULTS: In 74 subjects aged 68±6 years, LV volumes and mass indexed to height(2.7) (LVMI) were calculated from cardiac MRI. Despite the absence of clinically-defined LVH, there was a relationship (r=0.29; p=0.01) between systolic BP and LVMI. Both elevation of ADMA levels to the highest quartile or impairment of GTN responsiveness (determined by applanation tonometry) to the lowest quartile were determinants of LVMI independent of systolic BP (p=0.01 and p=0.03, respectively). Filling pressure (E/E' ratio from echocardiography) was increased in patients with impaired vascular NO responsiveness (p<0.05) irrespective of LVMI. ADMA remained a significant determinant of LVMI on multivariate analysis. CONCLUSIONS: These data imply that NO bioavailability within the myocardium modulates earliest stages of LVH development and facilitates development of diastolic dysfunction at a given LV mass.

A stable droplet reactor for high temperature nanocrystal synthesis.

We report a versatile capillary-based droplet reactor for the controlled synthesis of nanoparticles over a wide range of flow conditions and temperatures. The reactor tolerates large flow-rate differentials between individual reagent streams, and allows droplet composition to be varied independently of residence time and volume. The reactor was successfully applied to the synthesis of metal (Ag), metal-oxide (TiO(2)) and compound semiconductor (CdSe) nanoparticles, and in each case exhibited stable droplet flow over many hours of operation without fouling, even for reactions involving solid intermediates. For CdSe formed by the reaction of Cd oleate and Se, highly controlled growth could be achieved at temperatures of up to 250 °C, with emission spectra varying smoothly and reproducibly with temperature and flow-rate. The droplet reactor showed exceptional stability when operated under constant flow-rate and temperature conditions, yielding particles with well-defined band-edge emission spectra that did not vary over the course of a full day's continuous operation.

A case report of a normal aorta misdiagnosed as type A dissection by modern multidetector computed tomography.

Computed tomography (CT) is generally considered the investigation of choice to exclude acute aortic syndrome. We report an important potentially disastrous misdiagnosis using a modern 32 slice multidetector CT system.

Do cardiologists and cardiac surgeons need ethics? Achieving happiness for a drug user with endocarditis.

Ethical dilemmas are commonplace in clinical cardiology. There has been a recent focus on ethical behaviour of cardiologists and debate about resource allocation and cost-effectiveness of new technologies. The case of an intravenous drug addict, with native aortic valve endocarditis complicated by a cerebral abscess and severe aortic regurgitation, is presented to illustrate some common ethical and moral dilemmas. The predominant theories in medical ethics, including the "Four-Principles Approach," is discussed, and a model to translate these ethical theories into a clinical decision-making tool is presented.

Systemic lupus erythematosus prevalence in the UK: methodological issues when using the General Practice Research Database to estimate frequency of chronic relapsing-remitting disease.

PURPOSE: The purpose of this study was to calculate the prevalence of systemic lupus erythematosus (SLE) between 1992 and 1998 using the General Practice Research Database (GPRD) METHODS: We identified all individuals who had contributed at least 3 years of data to the GPRD and who had a diagnosis of SLE with supporting evidence of their diagnosis. We calculated the annual age- and sex-specific prevalence of SLE. Additionally, we stratified the prevalence by years of data contributed to the GRPD. RESULTS: In males the point estimate of the prevalence of SLE increased from 7.5/100,000 (CI(95) 6.3, 8.8) to 10.1/100,000 (CI(95) 7.8, 12.2) but this rise was not statistically significant. However, prevalence appeared to increase significantly amongst females from 42.6/100,000 (CI(95) 39.6, 45.6) in 1992 to 70.8/100,000 (CI(95) 65.1, 76.6) in 1998. This increase was mainly amongst women aged 50-79 and in those contributing more than 5 years of data and could not be explained by increasing incidence of SLE or decreasing mortality during the study period. CONCLUSIONS: We found an increasing prevalence of SLE that could not be explained by increasing incidence or decreasing mortality. This is almost certainly an artefact caused by the increased likelihood of detecting or confirming cases of chronic relapsing-remitting diseases with increasing time contributed to the GPRD.

Aortic sclerosis: not an innocent murmur but a marker of increased cardiovascular risk.

The detection of an ejection systolic murmur in the aortic valve region often corresponds to a diagnosis of aortic sclerosis or minor disruption of the aortic valve with associated turbulence but minimal obstruction. Aortic sclerosis has two important clinical implications. Firstly, aortic sclerosis is an antecedent to clinically significant aortic valve obstruction and, secondly, it acts as a marker of increased risk of cardiovascular events. This article reviews the evidence that aortic sclerosis is a useful adjunctive tool in cardiovascular risk stratification and that its progression to haemodynamically significant aortic stenosis is a potential focus for individual monitoring and for interventional studies.

Accident and emergency nurses as researchers: exploring some of the ethical issues when researching sensitive topics.

The breadth and complexity of accident and emergency (A&E) services is potentially a fruitful area for nursing and interdisciplinary research. A significant proportion of potential areas for research in A&E settings could be considered as 'sensitive topic areas'. Sensitive topic research raises many challenges; in particular, it raises specific ethical issues. This paper defines and identifies examples of sensitive topic area research in A&E and discusses some of the ethical issues to be considered before embarking on such research in A&E settings.