R P Steeds

Does immunosuppressant medication lower blood pressure and arterial stiffness in patients with chronic kidney disease? An observational study.

Chronic kidney disease is a proinflammatory state associated with increased arterial stiffness. We hypothesized that chronic kidney disease patients on long-term immunosuppression would have lower arterial stiffness and require treatment with less antihypertensive medication compared with non-immunosuppressed patients. A total of 254 patients (97 on immunosuppression) with chronic kidney disease were recruited from specialist renal clinics. Brachial blood pressure, central aortic pressure and waveform and pulse wave velocity were measured. Age, peripheral blood pressure and pulse wave velocity increased with worsening renal function but were not different between immunosuppressed and non-immunosuppressed patients. Central systolic (P<0.001) and pulse pressure (P=0.003) and the number of antihypertensive medications (P<0.001) increased with worsening renal function and were higher in non-immunosuppressed patients (P=0.02, P=0.004 and P<0.001, respectively). Age, mean arterial pressure, number of antihypertensive medications and a diagnosis of diabetes were found to be independent predictors of pulse wave velocity (R2=0.375; P<0.001). In a subgroup of 30 patient pairs without diabetes mellitus and cardiovascular disease and with a proven renal diagnosis, carefully matched for age, gender, renal function and systolic pressure, the prescribed antihypertensive medication remained lower in the immunosuppressed patients compared with non-immunosuppressed patients (P=0.04). Pulse wave velocity was lower in the immunosuppressed group (7.5±1.8 vs. 8.8±1.9u2009mu2009s–1; P=0.02). This study suggests that immunosuppression might be a method of reducing blood pressure and arterial stiffness in patients with chronic kidney disease.

Endothelial Nitric Oxide Synthase Single Nucleotide Polymorphism and Left Ventricular Function in Early Chronic Kidney Disease

Background Chronic kidney disease (CKD) is associated with accelerated cardiovascular disease and heart failure. Endothelial nitric oxide synthase (eNOS) Glu298Asp single nucleotide polymorphism (SNP) genotype has been associated with a worse phenotype amongst patients with established heart failure and in patients with progression of their renal disease. The association of a cardiac functional difference in non-dialysis CKD patients with no known previous heart failure, and eNOS gene variant is investigated. Methods 140 non-dialysis CKD patients, who had cardiac magnetic resonance (CMR) imaging and tissue doppler echocardiography as part of two clinical trials, were genotyped for eNOS Glu298Asp SNP retrospectively. Results The median estimated glomerular filtration rate (eGFR) was 50mls/min and left ventricular ejection fraction (LVEF) was 74% with no overt diastolic dysfunction in this cohort. There were significant differences in LVEF across eNOS genotypes with GG genotype being associated with a worse LVEF compared to other genotypes (LVEF: GG 71%, TG 76%, TT 73%, p = 0.006). After multivariate analysis, (adjusting for age, eGFR, baseline mean arterial pressure, contemporary CMR heart rate, total cholesterol, high sensitive C-reactive protein, body mass index and gender) GG genotype was associated with a worse LVEF, and increased LV end-diastolic and systolic index (p = 0.004, 0.049 and 0.009 respectively). Conclusions eNOS Glu298Asp rs1799983 polymorphism in CKD patients is associated with relevant sub-clinical cardiac remodelling as detected by CMR. This gene variant may therefore represent an important genetic biomarker, and possibly highlight pathways for intervention, in these patients who are at particular risk of worsening cardiac disease as their renal dysfunction progresses.

Unexpected benefits of participation in a clinical trial: abdominal aortic aneurysms in patients with chronic kidney disease.

A 75-year-old man was referred to renal services in 2008 with a creatinine of 168u2009µmol/l and an estimated glomerular filtration rate (eGFR) of 35u2009ml/min/1.73u2009m2. He had a past history of hypertension and carcinoma of the prostate previously treated with radiotherapy. There was no history of diabetes or cardiovascular disease. On referral, he was taking perindopril 8u2009mg, doxazosin 4u2009mg and bendroflumethiazide 2.5u2009mg with well-controlled blood pressure at 119/67u2009mmHg. Total cholesterol was 4.9u2009mmol/l. An abdominal ultrasound scan showed two kidneys (right 10.3u2009cm and left 11.6u2009cm) with moderate cortical thinning and no other pathology. He was followed up infrequently in the renal clinic as his renal function remained stable, his blood pressure was satisfactory and his cholesterol remained <5u2009mmol/l.nnIn June 2009, he agreed to participate in the CRIB-PHOS randomized controlled trial (evaluating the effects of sevelamer carbonate on cardiovascular structure and function in Chronic Renal Impairment in Birmingham).1 A lateral lumbar spine radiograph was performed to semi-quantitatively assess the presence and extent of abdominal aortic calcification at baseline as part of the study protocol.2 This showed heavy abdominal aortic calcification and a probable infra-renal aortic aneurysm measuring up to 6u2009cm (Figure 1a). Three days later, still as part of the trial, he underwent cardiac magnetic resonance imaging. With the patients consent, images were obtained of the abdominal aorta, which confirmed the presence of an infrarenal abdominal aortic aneurysm measuring 4.4u2009cm in the antero-posterior diameter with a rim of intraluminal thrombus (Figure 1b). nnnnFigure 1. nLateral lumbar spine radiograph ( a ) demonstrating the incidental finding of a markedly calcified abdominal aortic aneurysm (arrowheads). The aneurysm was confirmed to measure 4.4u2009cm …

Diagnosis and Treatment of the Cardiovascular Consequences of Fabry Disease

Fabry disease (FD) has been a diagnostic challenge since it was first recognized in 1898, with patients traditionally suffering from considerable delay before a diagnosis is made. Cardiac involvement is the current leading cause of death in FD. A combination of improved enzyme assays, availability of genetic profiling, together with more organized clinical services for rare diseases, has led to a rapid growth in the prevalence of FD. The earlier and more frequent diagnosis of asymptomatic individuals before development of the phenotype has focussed attention on early detection of organ involvement and closer monitoring of disease progression. The high cost of enzyme replacement therapy at a time of constraint within many health economies, moreover, has challenged clinicians to target treatment effectively. This article provides an outline of FD for the general physician and summarizes the aetiology and pathology of FD, the cardiovascular consequences thereof, modalities used in diagnosis and then discusses current indications for treatment, including pharmacotherapy and device implantation.

83 Use of feature tracking to assess systemic right ventricles in congenital heart disease patients with both single and dual ventricular circulations

Introduction The management of congenital patient’s frequently utilises cardiac magnetic resonance imaging to assess changes in patients cardiac function. Ventricular function assessment is challenging in this cohort due to complex ventricular geometry. Feature tracking uses routinely acquired MRI images to assess ventricular strain, a measure of cardiac contractility, which has been found in non-congenital cohorts to be a more sensitive marker of ventricular dysfunction than conventional imaging parameters. We hypothesised that 1) patients with a systemic ventricle of right ventricular (RV) morphology would have impaired strain parameters compared to controls and 2) patients with a systemic RV in a single ventricle circulation would have more impaired contractility than those with a dual ventricular circulation. Methods 3 groups were analysed: 1) 16 patients with hypoplastic left heart syndrome (HLHS) resulting in a single ventricle circulation (mean age 20±2u2009years; 81% male) 2) 16 patients with a systemic RV (sRV) in a dual ventricle circulation (age 32±5u2009years; 63% male) and 3) 16 healthy controls (mean age 30±4u2009years; 56% male). Participants underwent CMR at 1.5T for ventricular function assessment, analysis was undertaken using Circle cvi42 (v5.3) to calculate RV mid ventricular circumferential strain and peak longitudinal strain. Results The two patient groups had increased RV volumes with reduced ejection fraction (EF), elevated RV mass, but similar stroke volumes compared to controls (Table 1). The peak longitudinal RV strain was significantly reduced between the patient groups (HLHS mean −13±4; sRV −12±3) compared to controls (−18±5, p<0.001). However, there was no difference between the HLHS and sRV groups. Mid circumferential RV strain was not significantly different between both patient groups and also compared to controls (HLHS −13±4, sRV −12±4, controls −13±3, p 0.6). However comparison of mid circumferential RV strain to controls LV strain showed a significant reduction (controls LV mid circumferential strain mean −16±3, p 0.004) (Figure 1). The peak longitudinal strain in patients correlated with the RV end diastolic volume index (r=0.38, p 0.03), RV end systolic volume index (r=0.52, p 0.002), RV EF (r=0.535, p?0.002) and RV mass index (r=0.43, p 0.01). The mid RV circumferential strain only correlated with RV EF (r=0.40, p 0.02) and no other remodelling parameters. Discussion RV longitudinal strain was reduced in patients with a systemic RV irrespective of whether the ventricular configuration was single or dual. No difference was seen between the single circulation systemic RV compared to the dual circulation systemic RV, suggesting that RV remodelling is mostly in response to the systemic position rather than the ventricular configuration. Longitudinal studies will be required to assess the utility of the longitudinal strain in the prediction of outcomes in the follow up of these patients.Abstract 83 Table 1 Conventional right ventricular imaging parameters for the three study groupsAbstract 83 Figure 1 A) Mean longitudinal strain for the RV of patients with a single ventricle (HLHS), a systemic RV in a dual ventricular system (systemic RV) and the RV of healthy controls. B) Mean mid ventricular circumferential strain for the RV of patients with a single ventricle (HLHS), a systemic RV in a dual ventricular system (systemic RV) and RV and LV strain for healthy controls.

A randomized, multicenter, open-label, blinded end point trial comparing the effects of spironolactone to chlorthalidone on left ventricular mass in patients with early-stage chronic kidney disease: Rationale and design of the SPIRO-CKD trial

Background Chronic kidney disease (CKD) is associated with increased left ventricular (LV) mass and arterial stiffness. In a previous trial, spironolactone improved these end points compared with placebo in subjects with early-stage CKD, but it is not known whether these effects were specific to the drug or secondary to blood pressure lowering. Aim The aim was to investigate the hypothesis that spironolactone is superior to chlorthalidone in the reduction of LV mass while exerting similar effects on blood pressure. Design This is a multicenter, prospective, randomized, open-label, blinded end point clinical trial initially designed to compare the effects of 40 weeks of treatment with spironolactone 25 mg once daily to chlorthalidone 25 mg once daily on the co-primary end points of change in pulse wave velocity and change in LV mass in 350 patients with stages 2 and 3 CKD on established treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Because of slow recruitment rates, it became apparent that it would not be possible to recruit this sample size within the funded time period. The study design was therefore changed to one with a single primary end point of LV mass requiring 150 patients. Recruitment was completed on 31 December 2016, at which time 154 patients had been recruited. Investigations included cardiac magnetic resonance imaging, applanation tonometry, 24-hour ambulatory blood pressure monitoring, and laboratory tests. Subjects are assessed before and after 40 weeks of randomly allocated drug therapy and at 46 weeks after discontinuation of the study drug.

101 VALIDATION OF MAGNETIC RESONANCE FEATURE TRACKING FOR LONGITUDINAL SYSTOLIC AND DIASTOLIC STRAIN CALCULATION WITH SPATIAL MODULATION OF MAGNETISATION IMAGING ANALYSIS

Introduction Feature-tracking (FT) analysis offers a novel, fast and practicable method to calculate strain from routinely acquired steady state free precession (SSFP) images without the need to perform additional tagged sequences. There is no validation of this technique, however, against a reference standard myocardial tagging analysis for any strain parameter other than mid-left ventricular whole slice circumferential strain. In an adult study of patients with dilated cardiomyopathy (DCM) and healthy controls, we sought to validate the FT method (TomTec Imaging systems, Munich) against spatial modulation of magnetisation (SPAMM) tissue tagging analysis (Cardiac Image Modelling Package (CIMTag2D), University of Auckland) for the computation of long axis function. Methods We compared measures of global longitudinal strain from the horizontal long axis view using the two techniques in 45 patients (mean age 44±14u2005years, male 63%). Normal healthy adults (n=35) were identified from an ongoing prospective, observational research study examining the effects of living kidney donation on cardiovascular structure and function (NCT01028703). Consecutive DCM patients (n=10) were identified after undergoing myocardial tagging for clinically indicated scans. Retrospective off-line analysis was performed on matched tagged and SSFP slices by two independent blinded observers (WEM and RJT). After manually drawing endocardial borders in the end-diastolic frame for each image, the FT software automatically propagated the contour and followed its features (brightness gradient at the tissue-cavity interface, dishomogeneties of the tissue, spatial coherence) throughout the remainder of the cardiac cycle to compute longitudinal strain parameters. Results Longitudinal strain (Ell). Peak systolic FT-Ell (−18.1±5.0%) correlated most strongly with CIMTag-Ell values derived from the subendocardium (−16.7±4.8%) with a Pearsons correlation coefficient of 0.70 (p<0.001; figure 1A). A Bland Altman plot (figure 1B) showed good agreement with only a small systematic overestimation from FT (mean difference 1.3±3.8%, p=0.03). Whilst in DCM patients peak systolic global Ell values were not significantly different between the two techniques (−9.7±4.5% vs −8.8±3.9%, p=0.44), among healthy controls there was a small but significant difference in Ell values between FT and tagging image analysis (−19.5±3.5% vs −18.0±3.5%, p=0.04; figure 2). Figure 1 Figure 2 Longitudinal strain rate (SR) There was good agreement between the two techniques for peak systolic global longitudinal SR values but with a small tendency towards higher FT values as compared with tagging (mean difference 0.09±0.26 1/s, p=0.04; r=0.64, p<0.001). The weakest correlation between the two techniques was for early diastolic global longitudinal SR but even this relationship was still highly significant (mean difference 0.09±0.26 1/s; r=0.42, p=0.007). Reproducibility testing Intraobserver and interobserver variability for FT-Ell analysis was small (−0.49±1.83% and 0.22±1.13%, respectively). Timed analysis The average time taken for post-processing strain analysis using FT software was significantly less than that required for CIMTag (5.9±0.8u2005min vs 23.2±3.5u2005min, p<0.0001). Conclusions FT based assessment of longitudinal strain correlated highly with values derived from tagged images in a population with a wide range of left ventricular function. Furthermore, FT can be performed without the need for additional imaging and lengthy post-processing times.