Rajan K. Patel

Prognostic value of cardiovascular screening in potential renal transplant recipients: a single-center prospective observational study.

We assessed the outcome of pretransplant cardiac assessment in a single center. Three hundred patients with end‐stage renal disease underwent electrocardiogram, Bruce exercise testing (ETT) and ventricular assessment by cardiac MRI. Patients with high index of suspicion of coronary artery disease (CAD) underwent coronary angiography and percutaneous coronary intervention (PCI) if indicated. Two hundred and twenty‐two patients were accepted onto the renal transplant waiting list; 80 patients were transplanted during the follow‐up period and 60 died (7 following transplantation). Successful transplantation was associated with improved survival (mean survival 4.5 ± 0.6 years vs. listed not transplanted 4.1 ± 1.4 years vs. not listed 3.1 ± 1.7 years; p < 0.001). Ninety‐nine patients underwent coronary angiography; 65 had normal or low‐grade CAD and 34 obstructive CAD. Seventeen patients (5.6%) were treated by PCI. There was no apparent survival difference between patients who underwent PCI or coronary artery bypass graft compared to those who underwent angiography without intervention or no angiography (p = 0.67). Factors associated with nonlisting for renal transplantation included burden of preexisting cardiovascular disease, poor exercise tolerance and severity of CAD. Pretransplant cardiovascular screening provides prognostic information and information that can be used to restrict access to transplantation. However, if the aim is to identify and treat CAD, the benefits are far from clear.

Long-Term and Ultra Long–Term Blood Pressure Variability During Follow-Up and Mortality in 14 522 Patients With Hypertension

Recent evidence indicates that long-term visit-to-visit blood pressure variability (BPV) may be an independent cardiovascular risk predictor. The implication of this variability in hypertension clinical practice is unclear. BPV as average real variability (ARV) was calculated in 14 522 treated patients with hypertension in 4 time frames: year 1 (Y1), years 2 to 5 (Y2–5), years 5 to 10 (Y5–10), and years >10 (Y10+) from first clinic visit. Cox proportional hazards models for cause-specific mortality were used in each time frame separately for long-term BPV, across time frames based on ultra long–term BPV, and within each time frame stratified by mean BP. ARV in systolic blood pressure (SBP), termed ARVSBP, was higher in Y1 (21.3±11.9 mm Hg) in contrast to Y2–5 (17.7±9.9 mm Hg), Y5–10 (17.4±9.6 mm Hg), and Y10+ (16.8±8.5 mm Hg). In all time frames, ARVSBP was higher in women (P<0.01) and in older age (P<0.001), chronic kidney disease (P<0.01), and prevalent cardiovascular disease (P<0.01). Higher long-term and ultra long–term BPV values were associated with increased mortality (all-cause, cardiovascular, and noncardiovascular mortality; P for trend, <0.001). This relationship was also evident in subgroups with mean SBP<140 mm Hg in all time frames. Monitoring BPV in clinical practice may facilitate risk reduction strategies by identifying treated hypertensive individuals at high risk, especially those with BP within the normal range.

Determinants of Left Ventricular Mass and Hypertrophy in Hemodialysis Patients Assessed by Cardiac Magnetic Resonance Imaging

BACKGROUND AND OBJECTIVES Left ventricular hypertrophy (LVH) is an independent risk factor for premature cardiovascular death in hemodialysis (HD) patients and one of the three forms of uremic cardiomyopathy. Cardiovascular magnetic resonance (CMR) is a volume-independent technique to assess cardiac structure. We used CMR to assess the determinants of left ventricular mass (LVM) and LVH in HD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 246 HD patients (63.8% male; mean age 51.5 +/- 12.1 yr) underwent CMR on a postdialysis day. LVM was measured from a stack of cine loops and indexed for body surface area (LVM index [LVMI]). Demographic, past biochemical, hematologic, and dialysis data were collected by patient record review. Results up to 180 d before CMR were collected. LVH was defined as LVMI >84.1 g/m(2) (male) or >76.4 g/m(2) (female). RESULTS A total of 157 (63.8%) patients had LVH. LVH was more common in patients with higher predialysis systolic BP, predialysis pulse pressure, and calcium-phosphate product (Ca X PO4). Furthermore, LVH was significantly associated with higher end-diastolic and systolic volumes and lower ejection fraction. There were positive correlations with LVMI and end-diastolic and systolic volumes. There were weak positive correlations among LVMI, mean volume of ultrafiltration, and Ca X PO4. Using multivariate linear and logistic regression (entering one BP and cardiac variable), the independent predictors of LVMI and LVH were end-diastolic volume, predialysis systolic BP, and Ca X PO4. CONCLUSIONS The principal determinants of LVM and LVH in HD patients are end-diastolic LV volume, predialysis BP, and Ca X PO4.

Association of Left Atrial Volume With Mortality Among ESRD Patients With Left Ventricular Hypertrophy Referred for Kidney Transplantation

Background Left ventricular hypertrophy (LVH) is common in patients with end-stage renal disease (ESRD) and an independent risk factor for premature cardiovascular death. Left atrial volume (LAV), measured using echocardiography, predicts death in patients with ESRD. Cardiovascular magnetic resonance (CMR) imaging is a volume-independent method of accurately assessing cardiac structure and function in patients with ESRD. Study Design Single-center prospective observational study to assess the determinants of all-cause mortality, particularly LAV, in a cohort of ESRD patients with LVH, defined using CMR imaging. Setting & Participants 201 consecutive ESRD patients with LVH (72.1% men; mean age, 51.6 ± 11.7 years) who had undergone pretransplant cardiovascular assessment were identified using CMR imaging between 2002-2008. LVH was defined as left ventricular mass index >84.1 g/m2 (men) or >74.6 g/m2 (women) based on published normal left ventricle dimensions for CMR imaging. Maximal LAV was calculated using the biplane area-length method at the end of left ventricle systole and corrected for body surface area. Predictors CMR abnormalities, including LAV. Outcome All-cause mortality. Results 54 patients died (11 after transplant) during a median follow-up of 3.62 years. Median LAV was 30.4 mL/m2 (interquartile range, 26.2-58.1). Patients were grouped into high (median or higher) or low (less than median) LAV. There were no significant differences in heart rate and mitral valve Doppler early to late atrial peak velocity ratio. Increased LAV was associated with higher mortality. Kaplan-Meier survival analysis showed poorer survival in patients with higher LAV (log rank P = 0.01). High LAV and left ventricular systolic dysfunction conferred similar risk and were independent predictors of death using multivariate analysis. Limitations Only patients undergoing pretransplant cardiac assessment are included. Limited assessment of left ventricular diastolic function. Conclusions Higher LAV and left ventricular systolic dysfunction are independent predictors of death in ESRD patients with LVH.

Renal transplantation is not associated with regression of left ventricular hypertrophy: a magnetic resonance study.

BACKGROUND AND OBJECTIVES Patients with end-stage renal failure (ESRD) have an increased risk of premature cardiovascular (CV) disease. Left ventricular hypertrophy is an independent risk factor for CV events and death in ESRD. Renal transplantation has been associated with reduction in CV risk and echocardiographic regression of left ventricular hypertrophy. However, echocardiography overestimates LV mass in ESRD patients. Cardiac magnetic resonance (CMR) provides more detailed, volume-independent, measures of cardiac structure. Changes in LV mass measured by CMR after renal transplantation were studied. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Fifty patients underwent CMR on two occasions. Twenty-five were transplanted before the second scan. CMR was performed to measure LV mass index (LVMI), ejection fraction, end-diastolic and end-systolic volumes. Changes were expressed as percentage change over time. Patients with CV events between scans (e.g., acute coronary syndrome, myocardial infarction) were excluded. All transplant patients had serum creatinine <150 mumol/L. RESULTS There was no significant change in LVMI between patients who underwent renal transplantation and those who remained on dialysis (transplanted mean, 2.75%/yr, +/- 9.1 versus dialysis, -3.6%/yr +/- 16.7). In addition, there were no significant changes in end-diastolic volume (transplant, 0.1%/yr +/- 19.5 versus not transplanted, -3.4%/yr +/- 31.5), end-systolic volume (transplanted mean, 15.2%/yr +/- 65.2 versus not transplanted, 3.0%/yr +/- 55.5), or ejection fraction (transplant, 2.1%/yr +/- 11.9 versus not transplanted, -0.4%/yr +/- 5.3). CONCLUSIONS Renal transplantation is not associated with significant regression of LVMI on CMR compared with patients who remain on the transplant waiting list.

Inter-study reproducibility of arterial spin labelling magnetic resonance imaging for measurement of renal perfusion in healthy volunteers at 3 Tesla

BackgroundMeasurement of renal perfusion is a crucial part of measuring kidney function. Arterial spin labelling magnetic resonance imaging (ASL MRI) is a non-invasive method of measuring renal perfusion using magnetised blood as endogenous contrast. We studied the reproducibility of ASL MRI in normal volunteers.MethodsASL MRI was performed in healthy volunteers on 2 occasions using a 3.0 Tesla MRI scanner with flow-sensitive alternating inversion recovery (FAIR) perfusion preparation with a steady state free precession (True-FISP) pulse sequence. Kidney volume was measured from the scanned images. Routine serum and urine biochemistry were measured prior to MRI scanning.Results12 volunteers were recruited yielding 24 kidneys, with a mean participant age of 44.1 ± 14.6 years, blood pressure of 136/82 mmHg and chronic kidney disease epidemiology formula estimated glomerular filtration rate (CKD EPI eGFR) of 98.3 ± 15.1 ml/min/1.73 m2. Mean kidney volumes measured using the ellipsoid formula and voxel count method were 123.5 ± 25.5 cm3, and 156.7 ± 28.9 cm3 respectively. Mean kidney perfusion was 229 ± 41 ml/min/100 g and mean cortical perfusion was 327 ± 63 ml/min/100 g, with no significant differences between ASL MRIs. Mean absolute kidney perfusion calculated from kidney volume measured during the scan was 373 ± 71 ml/min. Bland Altman plots were constructed of the cortical and whole kidney perfusion measurements made at ASL MRIs 1 and 2. These showed good agreement between measurements, with a random distribution of means plotted against differences observed. The intra class correlation for cortical perfusion was 0.85, whilst the within subject coefficient of variance was 9.2%. The intra class correlation for whole kidney perfusion was 0.86, whilst the within subject coefficient of variance was 7.1%.ConclusionsASL MRI at 3.0 Tesla provides a repeatable method of measuring renal perfusion in healthy subjects without the need for administration of exogenous compounds. We have established normal values for renal perfusion using ASL MRI in a cohort of healthy volunteers.

Serum Chloride Is an Independent Predictor of Mortality in Hypertensive Patients

Chloride (Cl−) is the major extracellular anion in the body, accompanying sodium (Na+), and is primarily derived from dietary sources. Data suggest that increased dietary Cl− intake increases blood pressure, yet paradoxically, higher serum Cl− appears associated with lower mortality and cardiovascular risk. This implies that serum Cl− also reflects risk pathways independent of blood pressure, serum Na+, and bicarbonate (HCO3−). We analyzed 12 968 hypertensive individuals followed up for 35 years, using Cox proportional hazards model to test whether baseline serum Cl− was an independent predictor of mortality. To distinguish the effect of Cl− from Na+ and HCO3−, we adjusted for these electrolytes and also performed the analysis stratified by Na+/HCO3− and Cl− levels. Generalized estimating equation was used to determine the effect of baseline Cl− on follow-up blood pressure. The total time at risk was 197 101 person-years. The lowest quintile of serum Cl− (<100 mEq/L) was associated with a 20% higher mortality (all-cause, cardiovascular and noncardiovascular) compared with the remainder of the subjects. A 1 mEq/L increase in serum Cl− was associated with a 1.5% (hazard ratio, 0.985; 95% confidence interval, 0.98–0.99) reduction in all-cause mortality, after adjustment for baseline confounding variables and Na+, K+, and HCO3− levels. The group with Na+>135 and Cl−>100 had the best survival, and compared with this group, the Na+>135 and Cl−<100 group had significantly higher mortality (hazard ratio, 1.21; 95% confidence interval, 1.11–1.31). Low, not high Serum Cl− (<100 mEq/L), is associated with greater mortality risk independent of obvious confounders. Further studies are needed to elucidate the relation between Cl− and risk.

Risk Factors of Ischemic Stroke and Subsequent Outcome in Patients Receiving Hemodialysis

Background and Purpose— End-stage renal disease (ESRD) requiring hemodialysis carries up to a 10-fold greater risk of stroke than normal renal function. Knowledge on risk factors and management strategies derived from the general population may not be applicable to those with ESRD. We studied a large ESRD population to identify risk factors and outcomes for stroke. Methods— All adult patients receiving hemodialysis for ESRD from January 1, 2007, to December 31, 2012, were extracted from the electronic patient record. Variables associated with stroke were identified by survival analysis; demographic, clinical, imaging, and dialysis-related variables were assessed, and case-fatality was determined. Follow-up was until December 31, 2013. Results— A total of 1382 patients were identified (mean age, 60.5 years; 58.5% men). The prevalence of atrial fibrillation was 21.2%, and 59.4% were incident hemodialysis patients. One hundred and sixty patients (11.6%) experienced a stroke during 3471 patient-years of follow-up (95% ischemic). Stroke incidence was 41.5/1000 patient-years in prevalent and 50.1/1000 patient-years in incident hemodialysis patients. Factors associated with stroke on regression analysis were prior stroke, diabetes mellitus, and age at starting renal replacement therapy. Atrial fibrillation was not significantly associated with stroke, and warfarin did not affect stroke risk in warfarin-treated patients. Fatality was 18.8% at 7 days, 26.9% at 28 days, and 56.3% at 365 days after stroke. Conclusions— Incidence of stroke is high in patients with ESRD on hemodialysis with high case-fatality. Incident hemodialysis patients had the highest stroke incidence. Many, but not all, important risk factors commonly associated with stroke in the general population were not associated with stroke in patients receiving hemodialysis.

Haemoglobin Mass and Running Time Trial Performance after Recombinant Human Erythropoietin Administration in Trained Men

Recombinant human erythropoietin (rHuEpo) increases haemoglobin mass (Hbmass) and maximal oxygen uptake ( O2 max). Purpose This study defined the time course of changes in Hbmass, O2 max as well as running time trial performance following 4 weeks of rHuEpo administration to determine whether the laboratory observations would translate into actual improvements in running performance in the field. Methods 19 trained men received rHuEpo injections of 50 IU•kg−1 body mass every two days for 4 weeks. Hbmass was determined weekly using the optimized carbon monoxide rebreathing method until 4 weeks after administration. O2 max and 3,000 m time trial performance were measured pre, post administration and at the end of the study. Results Relative to baseline, running performance significantly improved by ∼6% after administration (10∶30±1∶07 min:sec vs. 11∶08±1∶15 min:sec, p<0.001) and remained significantly enhanced by ∼3% 4 weeks after administration (10∶46±1∶13 min:sec, p<0.001), while O2 max was also significantly increased post administration (60.7±5.8 mL•min−1•kg−1 vs. 56.0±6.2 mL•min−1•kg−1, p<0.001) and remained significantly increased 4 weeks after rHuEpo (58.0±5.6 mL•min−1•kg−1, p = 0.021). Hbmass was significantly increased at the end of administration compared to baseline (15.2±1.5 g•kg−1 vs. 12.7±1.2 g•kg−1, p<0.001). The rate of decrease in Hbmass toward baseline values post rHuEpo was similar to that of the increase during administration (−0.53 g•kg−1•wk−1, 95% confidence interval (CI) (−0.68, −0.38) vs. 0.54 g•kg−1•wk−1, CI (0.46, 0.63)) but Hbmass was still significantly elevated 4 weeks after administration compared to baseline (13.7±1.1 g•kg−1, p<0.001). Conclusion Running performance was improved following 4 weeks of rHuEpo and remained elevated 4 weeks after administration compared to baseline. These field performance effects coincided with rHuEpo-induced elevated O2 max and Hbmass.

Association between proteinuria and left ventricular mass index: a cardiac MRI study in patients with chronic kidney disease

BACKGROUND Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. We hypothesized that the level of proteinuria would correlate with left ventricular mass, providing a potential link between elevated protein excretion, left ventricular hypertrophy (LVH) and the increased mortality seen in patients with CKD. In order to do this, we assessed the determinants of left ventricular mass, measured using cardiac magnetic resonance (CMR) imaging, in patients with CKD. METHODS Patients attending the renal clinic with CKD stages 2-4 and diabetic nephropathy (n = 26) and IgA nephropathy (n = 23) were recruited. They underwent detailed demographic, biochemical and vascular phenotyping and CMR imaging. Proteinuria was measured using spot protein:creatinine ratio (PCR). Left ventricular mass index (LVMI) was calculated from short-axis cine imaging using Argus software and adjusted for body surface area. RESULTS Log-PCR correlated significantly with LVMI, as did waist circumference, pulse pressure and systolic blood pressure. LVMI was higher in men. When these variables were entered into a linear regression model, log-PCR (P = 0.006) and systolic blood pressure (P < 0.001) independently predicted LVMI. Renal function was not associated with LVMI. CONCLUSIONS Using volume-independent CMR imaging, we have demonstrated that the level of urinary protein excretion is independently and significantly associated with left ventricular mass in patients with CKD. This relationship was independent of blood pressure. This finding provides a novel link between CKD and increased cardiovascular risk.