Manvir Hayer

Do Obese Individuals With Hypertension Have More Difficult-to-Control Blood Pressure and End Organ Damage Than Their Nonobese Counterparts?

The authors assessed whether individuals with elevated body mass index (BMI) and hypertension had more difficult‐to‐control blood pressure (BP) and more evidence of end organ damage using data collected prospectively over 11 years from a secondary care hypertension clinic. A total of 1114 individuals were divided by BMI criteria into normal (n=207), overweight (n=440), and obese (n=467). Mean daytime, nighttime, and 24‐hour systolic BP and diastolic BP were similar in all groups. There was less nocturnal dip in obese compared with overweight groups (P=.025). Individuals with a normal BMI were taking fewer antihypertensive medications than those in the obese group (P=.01). Individuals classified as obese had a higher left ventricular mass index than those with a normal BMI (female, P=.028; male, P<.001); this relationship remained after multivariate linear regression. Obese individuals with hypertension required more medication to achieve similar mean ambulatory BP values, had less nocturnal dip in BP, and had a higher prevalence of left ventricular hypertrophy. As such, obese patients are at potentially increased risk of cardiovascular events.

Chronic kidney disease as a cardiovascular risk factor: lessons from kidney donors

Chronic kidney disease (CKD) is a major risk factor for cardiovascular disease but is often associated with other risks such as diabetes and hypertension and can be both a cause and an effect of cardiovascular disease. Although epidemiologic data of an independent association of reduced glomerular filtration rate with cardiovascular risk are strong, causative mechanisms are unclear. Living kidney donors provide a useful model for assessing the “pure” effects of reduced kidney function on the cardiovascular system. After nephrectomy, the glomerular filtration rate ultimately falls by about one-third so many can be classified as having chronic kidney disease stages 2 or 3. This prompts concern based on the data showing an elevated cardiovascular risk with these stages of chronic kidney disease. However, initial data suggested no increase in adverse cardiovascular effects compared with control populations. Recent reports have shown a possible late increase in cardiovascular event rates and an early increase in left ventricular mass and markers of risk such as urate and albuminuria. The long-term significance of these small changes is unknown. More detailed and long-term research is needed to determine the natural history of these changes and their clinical significance.

Reference ranges for three-dimensional feature tracking cardiac magnetic resonance: comparison with two-dimensional methodology and relevance of age and gender

Myocardial deformation is a sensitive marker of sub-clinical myocardial dysfunction that carries independent prognostic significance across a broad range of cardiovascular diseases. It is now possible to perform 3D feature tracking of SSFP cines on cardiac magnetic resonance imaging (FT-CMR). This study provides reference ranges for 3D FT-CMR and assesses its reproducibility compared to 2D FT-CMR. One hundred healthy individuals with 10 men and women in each of 5 age deciles from 20 to 70 years, underwent 2D and 3D FT-CMR of left ventricular myocardial strain and strain rate using SSFP cines. Good health was defined by the absence of hypertension, diabetes, obesity, dyslipidaemia, or any cardiovascular, renal, hepatic, haematological and systemic inflammatory disease. Normal values for myocardial strain assessed by 3D FT-CMR were consistently lower compared with 2D FT-CMR measures [global circumferential strain (GCS) 3D − 17.6 ± 2.6% vs. 2D − 20.9 ± 3.7%, P < 0.005]. Validity of 3D FT-CMR was confirmed against other markers of systolic function. The 3D algorithm improved reproducibility compared to 2D, with GCS having the best inter-observer agreement [intra-class correlation (ICC) 0.88], followed by global radial strain (GRS; ICC 0.79) and global longitudinal strain (GLS, ICC 0.74). On linear regression analyses, increasing age was weakly associated with increased GCS (R2 = 0.15, R = 0.38), peak systolic strain rate, peak late diastolic strain rate, and lower peak early systolic strain rate. 3D FT-CMR offers superior reproducibility compared to 2D FT-CMR, with circumferential strain and strain rates offering excellent intra- and inter-observer variability. Normal range values for myocardial strain measurements using 3D FT-CMR are provided.

10 Cardiac alterations after renal transplant; contoversies unravelled by cardiac mri

Background Successful kidney transplantation is associated with reduced cardiovascular (CV) morbidity and mortality compared to patients who remain on dialysis but is higher than in the general population. Longitudinal data reporting changes in uremic cardiomyopathy after renal transplant are conflicting; studies with echo have reported regression of left ventricular (LV) hypertrophy and improved systolic function but have not been replicated using cardiac MRI which is volume independent and does not depend on geometric assumptions. The CV response early after transplant with restoration of normal renal function have not been reported. The aim of this study was to assess changes in LV structure and function before and acutely (<8 weeks) after renal transplantation in patients with end-stage kidney disease (ESKD). Method All subjects were prospectively recruited prior to live-donor kidney transplantation. Patients had no history of CV disease or diabetes and underwent cardiac MRI pre-operatively and within eight weeks post-operatively. Stress echocardiography or a myocardial perfusion scan was performed to exclude ischaemic heart disease. Haemodialysis patients were scanned on the day after dialysis, and peritoneal dialysis patients were scanned at their dry weight. Cardiac MRI data were analysed using CVi42 (Calgary, Canada). Results In total 10 patients were studied (male gender 70%, age 45 years [30-60], dialysis 40%). Cardiac MRI data is presented in Table 1. Pre-operative studies demonstrated; median left ventricular mass 82 g/m2 with 6 patients reaching criteria for LV hypertrophy. Increased segmental wall thickness >11 mm in 8 patients. Mean LV ejection fraction (LVEF) 66%±10, only 2 patients had mild LV impairment (LVEF 50%–55%). The mean estimated glomerular filtration rate (eGFR) increased from 11 ml/min/1.73 m2 to 53 ml/min/1.73 m2 after transplantation without a change in body weight. Left ventricular and atrial volumes decreased at follow up without a change in LV mass. The reduction in indexed left ventricular diastolic volume (LVEDVi) was associated with an increase in ejection fraction (EF) (r=−0.810, p<0.001), and with an increased MAPSE (r=−0.868, p=0.001). Discussion A reduction in LV volumes acutely after renal transplantation is associated with improved prognostic markers of LV function and atrial size. Patients with ESKD are chronically fluid overloaded even at dry weigh. Cardiac MRI is the method of choice for longitudinal studies in defining the natural history of uremic cardiomyopathy after renal transplantation. Values are expressed as mean±SD or median (interquartile range). P Value <0.05 demonstrates significance in change of variable following transplantation.Abstract 10 Table 1 Cardiac MRI data for the change in left ventricular volumes, mass and function between pre-operative and follow up scan (<8 weeks post-transplant) Pre-operative Post-operative Change P Value LVEDV (ml) 167±79 72±17 −95±66 0.001 LVEDVi (ml/m2) 91±33 72±17 −19±19 0.012 LVESV (ml) 65±41 40±20 −25±29 0.025 LVESV (ml/m2) 33±20 21±9 −12±16 0.044 LV Mass (g) 160 (124 to 189) 164 (113 to 180) −9 (−25 to 9) 0.305 LV Mass Indexed (g/m2) 82 (60 to 91) 77 (64 to 94) −6 (−13 to 5) 0.185 EF (%) 66±10 72±8 6±7 0.028 MAPSE (mm) 13±2 13±3 0±4 0.813 Left Atrial Volume Indexed (ml/m2) 51±18 34±12 −14±15 0.012 Global Longitudinal Strain (%) −17.7±5.3 −17.7±1.8 −0.01±4.4 0.994 Segmental Wall Thickness (mm) 14±4 14±2 0±3 0.916 Values are expressed as mean SD or median (interquartile range). P Value >0.05 ?demonstrates significance in change of variable following transplantation.

Diffuse Myocardial Interstitial Fibrosis and Dysfunction in Early Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have a disproportionately high risk of cardiovascular (CV) morbidity and mortality from the very early stages of CKD. This excess risk is believed to be the result of myocardial disease commonly termed uremic cardiomyopathy (UC). It has been suggested that interstitial myocardial fibrosis progresses with advancing kidney disease and may be the key mediator of UC. This longitudinal study reports data on the myocardial structure and function of 30 patients with CKD with no known cardiovascular disease and healthy controls. All patients underwent cardiac magnetic resonance imaging including T1 mapping and late gadolinium enhancement (if estimated glomerular filtration rate > 30 ml/min/1.73 m2). Over a mean follow-up period of 2.7 ± 0.8 years, there was no change in left ventricular mass, volumes, ejection fraction, native myocardial T1 times, or extracellular volume with CKD or in healthy controls. Global longitudinal strain (20.6 ± 2.9 s−1 vs 19.8 ± 2.9 s−1, p = 0.03) and mitral annular planar systolic excursion (13 ± 2 mm vs 12 ± 2 mm, p = 0.009) decreased in CKD but were clinically insignificant. Midwall late gadolinium enhancement was present in 4 patients at baseline and was unchanged at follow-up. Renal function was stable in this cohort over follow-up (change in estimated glomerular filtration rate was −3 ml/min/1.73 m2) with no adverse clinical CV events. In conclusion, this study demonstrates that in a cohort of patients with stable CKD, left ventricular mass, native T1 times, and extracellular volume do not increase over a period of 2.7 years.

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.

135 Detecting Progression of Diffuse Interstitial Fibrosis in Alstrom Syndrome

Introduction Alstrom Syndrome (ALMS) is a rare inherited disorder caused by a mutation in the ALMS1 gene. The syndrome is a multi-system disorder with exaggerated features of the metabolic syndrome and although rare, provides a monogenic model for end-organ fibrosis and as a paradigm for the effects of severe metabolic syndrome. Adults with ALMS have a high risk of death from heart failure in their twenties due to a cardiomyopathy which (in the small post-mortem series available) is characterised by coarse fibrosis on histology. Our previous work has identified expansion of the extracellular space (ECV) consistent with diffuse interstitial fibrosis in over half of asymptomatic ALMS patients compared to controls. The aim of this study was to investigate the longitudinal change in ECV and assess the impact on ventricular structure and function. Methods A prospective longitudinal cohort study of patients attending the national service for ALMS at the Centre for Rare Disease in Birmingham from 2012. At referral and on annual follow up, all subjects underwent comprehensive LV and RV assessment with cardiac MRI (CMR 1.5T Siemens Avanto). The presence of diffuse interstitial myocardial fibrosis was assessed using native myocardial T1 relaxation mapping and extracellular volume (ECV) in the LV septum (MOLLI) using cvi42 (Circle Cardiovascular Imaging). Coarse replacement fibrosis was assessed using standard late gadolinium enhancement imaging. Results In total 14 patients (male gender 71%, age 28 ± 8years) had baseline and follow up data (median 1.7 [1.1–2.8] years). CMR data is presented in Table 1. The native LV myocardial T1 values and ECV were increased in the septum at basal and mid levels at follow up. Left ventricular mass increased (54 ± 9 g/m2 vs. 62 ± 12 g/m2) but with a reduction in septal myocardial intracellular volume (ICV 0.74 ± 0.06 vs. 0.68 ± 0.04, p < 0.05) suggesting ECV expansion rather than myocyte hypertrophy was the driver. There were no differences in LV or RV volumes or RVEF. Four patients had LGE; two patients had focal at RV insertion points LGE and two patients had mid-wall LGE in the basal infero-lateral segments. Conclusion ALMS is associated with increases in ECV and progressive change in T1 values over time that reflects progression of diffuse interstitial fibrosis in asymptomatic adults. Cross-sectional studies have identified ECV as a biomarker of cardiovascular “vulnerability” but longitudinal tracking has the potential to highlight those at greatest risk.Abstract 135 Table 1 Baseline and Follow-up CMR data Baseline Follow-up LV Septal T1 (ms) 952 (80) 1040 (1070)** LV Basal septal T1 (ms) 953 (63) 1042 (76)** LV Mid septal TI (ms) 949 (68) 1033 (58)** Septal ECV 0.26 (0.06) 0.32 (0.04)* LV EDVi (ml/m2) 57 (10) 56 (10) LVESV(ml/m2) 20 (7) 20 (8) LVEF (%) 65 (8) 67 (5) LV Mass index 54 (9) 62 (12) RVEDV(ml/m2) 57 (10) 56 (12) RVESV(ml/m2) 23 (6) 21 (6) RVEF(ml/m2) 61 (7) 63 (7) Mean (SD), ** p<0.01

Acute Care QUAliTy in chronic Kidney disease (ACQUATIK): a prospective cohort study exploring outcomes of patients with chronic kidney disease.

Introduction Chronic kidney disease (CKD) is common and carries a high risk of morbidity, including hospital admissions and readmissions and mortality. This is largely attributed to an increased risk of cardiovascular disease. Patients with CKD are less likely to receive evidence-based treatments for cardiovascular disease. However, these treatments are based on trials which generally exclude patients with CKD. It is therefore unclear whether this patient group derives the same benefits without an increased risk of adverse effects. Methods and analysis The Acute Care QUAliTy in chronic Kidney disease (ACQUATIK) study is a prospective, observational, multicentre cohort study. Over 4000 patients will be recruited with an enrolment period of 2 years and a follow-up period of 2–4 years. Patients under follow-up by a renal team will be excluded. Data will be obtained from patient and hospital records during the index admission. Preadmission data will be extracted from general practice records based on the Quality and Outcomes Framework. Diagnosis, comorbidities and procedure data pertaining to the index and subsequent admissions will be extracted from the Hospital Episode Statistics database and long-term mortality data will be tracked using the Office of National Statistics. This information will allow us to examine a complete patient journey through primary and secondary care, providing unequalled levels of information on treatment and outcomes of patients with CKD. The combined data set will be used to compare outcomes and treatments among patients with CKD versus patients without CKD. The primary end point is hospital readmission rates. The relationship between age, sex, ethnicity, socioeconomic status and concurrent comorbidities will be analysed to determine their influence on outcomes and treatments. Ethics and dissemination The ACQUATIK study has been approved by the NRES Committee West Midlands—South Birmingham—Reference 13/WM/0317. The results from ACQUATIK will be submitted for publication in peer-reviewed journals and presented at primary and secondary care conferences. Trial registration number ISRCTN37237454.