Alex Pitcher

Aortic Dilation in Bicuspid Aortic Valve Disease Flow Pattern Is a Major Contributor and Differs With Valve Fusion Type

Background— Ascending aortic dilation is important in bicuspid aortic valve (BAV) disease, with increased risk of aortic dissection. We used cardiovascular MR to understand the pathophysiology better by examining the links between 3-dimensional flow abnormalities, aortic function, and aortic dilation. Methods and Results— A total of 142 subjects underwent cardiovascular MR (mean age, 40 years; 95 with BAV, 47 healthy volunteers). Patients with BAV had predominantly abnormal right-handed helical flow in the ascending aorta, larger ascending aortas (18.3±3.3 versus 15.2±2.2 mm/m2; P <0.001), and higher rotational (helical) flow (31.7±15.8 versus 2.9±3.9 mm2/s; P <0.001), systolic flow angle (23.1°±12.5° versus 7.0°±4.6°; P <0.001), and systolic wall shear stress (0.85±0.28 versus 0.59±0.17 N/m2; P <0.001) compared with healthy volunteers. BAV with right-handed flow and right-non coronary cusp fusion (n=31) showed more severe flow abnormalities (rotational flow, 38.5±16.5 versus 27.8±12.4 mm2/s; P <0.001; systolic flow angle, 29.4°±10.9° versus 19.4°±11.4°; P <0.001; in-plane wall shear stress, 0.64±0.23 versus 0.47±0.22 N/m2; P <0.001) and larger aortas (19.5±3.4 versus 17.5±3.1 mm/m2; P <0.05) than right–left cusp fusion (n=55). Patients with BAV with normal flow patterns had similar aortic dimensions and wall shear stress to healthy volunteers and younger patients with BAV showed abnormal flow patterns but no aortic dilation, both further supporting the importance of flow pattern in the pathogenesis of aortic dilation. Aortic function measures (distensibility, aortic strain, and pulse wave velocity) were similar across all groups. Conclusions— Flow abnormalities may be a major contributor to aortic dilation in BAV. Fusion type affects the severity of flow abnormalities and may allow better risk prediction and selection of patients for earlier surgical intervention.Background—Ascending aortic dilation is important in bicuspid aortic valve (BAV) disease, with increased risk of aortic dissection. We used cardiovascular MR to understand the pathophysiology better by examining the links between 3-dimensional flow abnormalities, aortic function, and aortic dilation. Methods and Results—A total of 142 subjects underwent cardiovascular MR (mean age, 40 years; 95 with BAV, 47 healthy volunteers). Patients with BAV had predominantly abnormal right-handed helical flow in the ascending aorta, larger ascending aortas (18.3±3.3 versus 15.2±2.2 mm/m2; P<0.001), and higher rotational (helical) flow (31.7±15.8 versus 2.9±3.9 mm2/s; P<0.001), systolic flow angle (23.1°±12.5° versus 7.0°±4.6°; P<0.001), and systolic wall shear stress (0.85±0.28 versus 0.59±0.17 N/m2; P<0.001) compared with healthy volunteers. BAV with right-handed flow and right-non coronary cusp fusion (n=31) showed more severe flow abnormalities (rotational flow, 38.5±16.5 versus 27.8±12.4 mm2/s; P<0.001; systolic flow angle, 29.4°±10.9° versus 19.4°±11.4°; P<0.001; in-plane wall shear stress, 0.64±0.23 versus 0.47±0.22 N/m2; P<0.001) and larger aortas (19.5±3.4 versus 17.5±3.1 mm/m2; P<0.05) than right–left cusp fusion (n=55). Patients with BAV with normal flow patterns had similar aortic dimensions and wall shear stress to healthy volunteers and younger patients with BAV showed abnormal flow patterns but no aortic dilation, both further supporting the importance of flow pattern in the pathogenesis of aortic dilation. Aortic function measures (distensibility, aortic strain, and pulse wave velocity) were similar across all groups. Conclusions—Flow abnormalities may be a major contributor to aortic dilation in BAV. Fusion type affects the severity of flow abnormalities and may allow better risk prediction and selection of patients for earlier surgical intervention.

Elevated Blood Pressure in Offspring Born Premature to Hypertensive Pregnancy: Is Endothelial Dysfunction the Underlying Vascular Mechanism?

Offspring born to mothers with hypertensive pregnancy have higher childhood blood pressure. We hypothesized this relates to prenatally programmed differences in the underlying vascular pathophysiology of the offspring and that these would be most apparent in those born preterm because of severe hypertension. We carried out a 20-year follow-up study of 71 subjects born preterm, 19 to a hypertensive pregnancy and 52 to a normotensive pregnancy. Findings were compared with 38 subjects born at term to uncomplicated pregnancies. Peripheral and central blood pressures were measured, and then central arterial stiffness was assessed by carotid-femoral pulse wave velocity using applanation tonometry. Ultrasound was used to assess flow-mediated endothelial-dependent and independent brachial artery responses and common carotid artery intima-media thickness. Offspring born preterm to either hypertensive or normotensive pregnancy had higher peripheral and central blood pressure compared with full-term born offspring (central mean arterial pressure after preterm hypertensive pregnancy: 84.92±7.0 mm Hg; preterm normotensive pregnancy: 84.13±8.9 mm Hg; full-term pregnancy: 76.24±7.96 mm Hg; P=0.0009). However, underlying vascular phenotype differed. Preterm offspring of normotensive pregnancy had greater arterial stiffness than offspring of hypertensive pregnancy (5.92±0.84 versus 5.42±0.73 m/s; P=0.039), whereas offspring of hypertensive pregnancy had greater carotid intima-media thickness (0.52±0.04 versus 0.48±0.06 mm; P=0.013) and 30% lower flow-mediated dilatation (4.25±4.02% versus 6.79±4.38%; P=0.05). Prematurity is associated with elevated blood pressure in later life. However, predominant underlying vascular phenotype depends on maternal pathology. Targeting endothelial function may be particularly important for primary prevention after hypertension in pregnancy.

Gender-specific differences in left ventricular remodelling in obesity: insights from cardiovascular magnetic resonance imaging

AIMS As obesity-related cardiovascular mortality, although elevated when compared with normal weight, is lower in females than in males at every body mass index (BMI) level, we aimed to investigate gender-specific differences in left ventricular (LV) hypertrophy in obesity, which themselves have been shown to have varying prognostic value. METHOD AND RESULTS In total, 741 subjects (female, n = 399) without identifiable cardiovascular risk factors (BMI 15.7-59.2 kg/m(2)) underwent cardiovascular magnetic resonance (1.5 T) to determine LV mass, end-diastolic volume (EDV, mL), and LV mass/volume ratio (LVM/VR). Across both sexes, there was a strong positive correlation between BMI and LV mass (male r = 0.44, female r = 0.57, both P < 0.001), with males showing a greater LV hypertrophic response (male +2.3 vs. female +1.6 g per BMI point increase, P = 0.001). Concentric hypertrophy was present in both sexes and LVM/VR positively correlated to BMI (male r = 0.45, female r = 0.29, both P < 0.001) on linear regression analysis. However, the degree of concentric hypertrophy was greater in males (male +0.13 vs. female +0.06 LVM/VR increase per BMI point increase, P = 0.001). On the other hand, females showed a greater LV cavity dilatory response (female +1.1 vs. male +0.3 mL per BMI point increase, P < 0.001). Indeed, in contrast to females, where BMI and LV-EDV were positively correlated (r = 0.38, P < 0.001), BMI did not correlate with EDV in men (r = 0.03, P = 0.62). CONCLUSION In the absence of traditional cardiovascular risk factors, obese men show predominantly concentric hypertrophy, whereas obese women exhibit both eccentric and concentric hypertrophy. As concentric hypertrophy is more strongly related to cardiovascular mortality than eccentric hypertrophy, our observations may explain the observed gender difference in obesity-related mortality.

7 Tesla (T) human cardiovascular magnetic resonance imaging using FLASH and SSFP to assess cardiac function: validation against 1.5 T and 3 T

We report the first comparison of cardiovascular magnetic resonance imaging (CMR) at 1.5 T, 3 T and 7 T field strengths using steady state free precession (SSFP) and fast low angle shot (FLASH) cine sequences. Cardiac volumes and mass measurements were assessed for feasibility, reproducibility and validity at each given field strength using FLASH and SSFP sequences. Ten healthy volunteers underwent retrospectively electrocardiogram (ECG) gated CMR at 1.5 T, 3 T and 7 T using FLASH and SSFP sequences. B1 and B0 shimming and frequency scouts were used to optimise image quality. Cardiac volume and mass measurements were not significantly affected by field strength when using the same imaging sequence (P > 0.05 for all parameters at 1.5 T, 3 T and 7 T). SSFP imaging returned larger end diastolic and end systolic volumes and smaller left ventricular masses than FLASH imaging at 7 T, and at the lower field strengths (P < 0.05 for each parameter). However, univariate general linear model analysis with fixed effects for sequence and field strengths found an interaction between imaging sequence and field strength (P = 0.03), with a smaller difference in volumes and mass measurements between SSFP and FLASH imaging at 7 T than 1.5 T and 3 T. SSFP and FLASH cine imaging at 7 T is technically feasible and provides valid assessment of cardiac volumes and mass compared with CMR imaging at 1.5 T and 3 T field strengths. Copyright

A finite-element approach to the direct computation of relative cardiovascular pressure from time-resolved MR velocity data

Graphical abstract Highlights ► Extraction of relative pressure from 4D MRI data sets. ► A novel workflow for determining relative cardiovascular pressure fields. ► Demonstration of the approach across a range of validation examples. ► Four subject specific cases showing agreement with published pressure differences.

Cardiovascular MRI in clinical trials: expanded applications through novel surrogate endpoints

Recent advances in cardiovascular magnetic resonance (CMR) now allow the accurate and reproducible measurement of many aspects of cardiac and vascular structure and function, with prognostic data emerging for several key imaging biomarkers. These biomarkers are increasingly used in the evaluation of new drugs, devices and lifestyle modifications for the prevention and treatment of cardiovascular disease. This review outlines a conceptual framework for the application of imaging biomarkers to clinical trials, highlights several important CMR techniques which are in use in randomised studies, and reviews certain aspects of trial design, conduct and interpretation in relation to the use of CMR.

Aortic relative pressure components derived from four-dimensional flow cardiovascular magnetic resonance.

To describe the assessment of the spatiotemporal distribution of relative aortic pressure quantifying the magnitude of its three major components.

UK doctors’ views on the implementation of the European Working Time Directive as applied to medical practice: a qualitative analysis

Objectives To report on what doctors at very different levels of seniority wrote, in their own words, about their concerns about the European Working Time Directive (EWTD) and its implementation in the National Health Service (NHS). Design All medical school graduates from 1993, 2005 and 2009 were surveyed by post and email in 2010. Setting The UK. Methods Using qualitative methods, we analysed free-text responses made in 2010, towards the end of the first year of full EWTD implementation, of three cohorts of the UK medical graduates (graduates of 1993, 2005 and 2009), surveyed as part of the UK Medical Careers Research Groups schedule of multipurpose longitudinal surveys of doctors. Results Of 2459 respondents who gave free-text comments, 279 (11%) made unprompted reference to the EWTD; 270 of the 279 comments were broadly critical. Key themes to emerge included frequent dissociation between rotas and actual hours worked, adverse effects on training opportunities and quality, concerns about patient safety, lowering of morale and job satisfaction, and attempts reportedly made in some hospitals to persuade junior doctors to collude in the inaccurate reporting of compliance. Conclusions Further work is needed to determine whether problems perceived with the EWTD, when they occur, are attributable to the EWTD itself, and shortened working hours, or to the way that it has been implemented in some hospitals.

Mortality from heart failure, acute myocardial infarction and other ischaemic heart disease in England and Oxford: a trend study of multiple-cause-coded death certification

Background Age-standardised death rates from acute myocardial infarction (AMI) and ischaemic heart disease (IHD) have been declining in most developed countries. However, the magnitude of such reductions and how they impact on death from heart failure are less certain. We sought to assess and compare temporal trends in mortality from heart failure, AMI and non-AMI IHD over a 30-year period in England. Methods We analysed death registration data for multiple-cause-coded mortality for all deaths in people aged 35 years and over in England from 1995 to 2010, population 52 million, and in a regional population (Oxford region) from 1981 to 2010, population 2.5 million, for which data on all causes of death were available. Results Considering all ages and both sexes combined, during the 30-year observation period, age-standardised and sex-standardised mortality rates based on all certified causes of death declined by 60% for heart failure, 80% for AMI and 46% for non-AMI IHD. These longer term trends observed in the Oxford region were consistent with those for the whole of England from 1995 to 2010, with no evidence of a plateau in recent years. Although proportional reductions in rates differed by age and sex, even in those aged 85 years or more, there were substantial reductions in mortality rates in the all-England data set (50%, 66% and 20% for heart failure, AMI and non-AMI IHD, respectively). Conclusions This study shows large and sustained reductions in age-specific and sex-specific and standardised death rates from heart failure, as well as from AMI and non-AMI IHD, over a 30-year period in England.

HIV is an independent predictor of aortic stiffness

BackgroundPatients with treated Human Immunodeficiency Virus-1 (HIV) infection are at increased risk of cardiovascular events. Traditionally much of this risk has been attributed to metabolic and anthropometric abnormalities associated with HIV, which are similar to the metabolic syndrome (MS), an established risk factor for cardiovascular mortality. It remains unclear whether treated HIV infection is itself associated with increased risk, via increase vascular stiffness.Methods226 subjects (90 with HIV) were divided into 4 groups based on HIV and MS status: 1) HIV-ve/MS-ve, 2) HIV-ve/MS + ve, 3) HIV + ve/MS-ve and 4)HIV + ve/MS + ve. CMR was used to determine aortic pulse wave velocity (PWV) and regional aortic distensibility (AD).ResultsPWV was 11% higher and regional AD up to 14% lower in the HIV + ve/MS-ve group when compared to HIV-ve/MS-ve (p < 0.01 all analyses). PWV and AD in the HIV + ve/MS-ve group was similar to that observed in the HIV-ve/MS + ve group (p > 0.99 all analyses). The HIV + ve/MS + ve group had 32% higher PWV and 30-34% lower AD than the HIV-ve/MS-ve group (all p < 0.001), and 19% higher PWV and up to 31% lower AD than HIV + ve/MS-ve subjects (all p < 0.05). On multivariable regression, age, systolic blood pressure and treated HIV infection were all independent predictors of both PWV and regional AD.ConclusionAcross multiple measures, treated HIV infection is associated with increased aortic stiffness and is also an independent predictor of both PWV and regional AD. The magnitude of the effect of treated HIV and MS are similar, with additive detrimental effects on central vascular elasticity.