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1.  Effects of Sodium Thiosulfate on Vascular Calcification in End-Stage Renal Disease: A Pilot Study of Feasibility, Safety and Efficacy 
American Journal of Nephrology  2011;33(2):131-138.
Background and Objectives
Vascular calcification is a major contributor to morbidity and mortality in hemodialysis. The objective of this pilot study was to determine the feasibility, safety and efficacy of sodium thiosulfate (STS) in the progression of vascular calcification in hemodialysis patients.
Chronic hemodialysis patients underwent a battery of cardiovascular tests. Those with coronary artery calcium (Agatston scores >50) received intravenous STS after each dialysis for 5 months (n = 22) and the tests were repeated. Changes in MDCT-determined calcification were assessed as the mean annualized rate of change in 3 vascular beds (coronary, thoracic and carotid arteries) and in L1-L2 vertebral bone density.
Although individual analyses showed coronary artery calcification progression in 14/22 subjects, there was no progression in the mean annualized rate of change of vascular calcification in the entire group. The L1-L2 vertebral bone density showed no changes. There were no correlations between rates of progression of vascular calcification and phosphorus, fetuin or C-reactive protein levels. Changes in coronary artery calcification scores correlated with those of the thoracic aorta.
STS treatment is feasible, appears safe and may decrease the rate of progression of vascular calcification in hemodialysis patients. A large, randomized, controlled trial is warranted.
PMCID: PMC3064860  PMID: 21242673
Hemodialysis; Sodium thiosulfate; Vascular calcification
2.  Are Normative Values for LV Geometry and Mass Based on Fundamental Imaging Valid With Use of Harmonic Imaging? 
Multiple studies have reported echocardiographically determined normal reference values for left ventricular mass (LVM) derived using fundamental imaging (FI). Modern ultrasound systems now use harmonic imaging (HI) due to the improved LV endomyocardial definition. However, the 2005 American Society of Echocardiography (ASE) Recommendations noted that the applicability of the reference values to HI-derived measurements has not been established.
LV end-diastolic volume, diameter, wall thickness, and mass were determined using HI in healthy subjects (n=251) including a normal weight (NW, body mass index [BMI] < 25 kg/m2, n=149, 68% women) and an otherwise-healthy overweight (OW, BMI ≥25 and <30 kg/m2, n=102, 41% women) groups. Measurements were compared to ASE-endorsed reference values. The agreement between FI and HI was determined in a prospective cohort of 51 subjects.
2D-derived LV volumes were similar between NW and OW subjects; although M-mode (MM)-derived LV diameters were slightly greater in OW. 2D- and MM-derived LVM was greater in OW compared to NW subjects, including after adjustment by height or height2.7; however, indexing to body surface area eliminated these differences. The partition values for abnormal 2D- and MM-derived LVM were generally greater in NW and OW subjects of both sexes compared with the ASE endorsed values (except MM-derived in NW men). However, there were no significant differences in LVM determined by HI compared to FI in a prospectively studied cohort.
Reference values for LVM derived from NW and OW cohorts are generally higher than the ASE-endorsed referenced values. The difference between NW and ASE-endorsed values is unlikely to result from the use of HI rather than FI since there is excellent agreement between these two imaging modalities. This study emphasizes the need to update normal reference values to reflect modern imaging methods.
PMCID: PMC2993783  PMID: 20863657
echocardiography; fundamental imaging; harmonic imaging; left ventricular mass; body mass index
3.  Central Aortic Pressure is Independently Associated With Diastolic Function 
American heart journal  2010;159(6):1081-1088.
Studies investigating the association between central aortic pressures and diastolic function have been limited.
Consecutive ambulatory patients (n=281, mean age 49±13 yrs, 49% male) with normal LV systolic function were included. LV filling pressure (E/Em) was estimated by Doppler-derived ratio of mitral inflow velocity [E] to septal [Em] by tissue Doppler, LV relaxation by Em, central aortic pressures by radial tonometry. Central aortic systolic (cSBP), diastolic (cDBP), mean (cMAP), and pulse pressure (cPP) were entered individually into stepwise linear regression models to determine their association with E/Em or Em.
In univariate analysis, cPP correlated most strongly with E/Em (Spearman’s rho=0.45, p<0.001), while cSBP correlated most strongly with Em (Spearman’s rho=−0.51, p<0.001). Multivariate analysis demonstrated that the pulsatile component of afterload, cPP, contributed most to E/Em (partial r2=23%); meanwhile the nonpulsatile components (cDBP and cMAP), were significant but small contributors (partial r2 of 6% and 5% respectively) of LV relaxation (Em).
The nonpulsatile components of aortic afterload (central mean aortic pressure (cMAP) and central aortic diastolic blood pressure cDBP), exhibited a weak but significant association with LV relaxation, while the pulsatile component of afterload, central aortic pulse pressure (cPP), exhibited strong association with LV filling pressure.
PMCID: PMC2913412  PMID: 20569723
diastolic function; pulse pressure; aortic blood pressures
4.  Interatrial Conduction Time and Left Atrial Function in Patients with Left Ventricular Systolic Dysfunction: Effects of Cardiac Resynchronization Therapy 
Prolonged inter-atrial conduction time (IACT) can be associated with abnormal left atrial (LA) function but has not been characterized in patients with left ventricular systolic dysfunction (LVSD) and a QRS interval >130 ms.
2D-Doppler echocardiography and tissue Doppler imaging (TDI) was performed in 41 patients with LVSD (LV ejection fraction 26±5%) and 41 similarly-age normal controls (NC). 2D measurements included LV volumes, ejection fraction and LA volumes for determination of LA emptying fraction and LA ejection fraction. IACT was defined as onset of P-wave to onset of the TDI-derived late diastolic (A') velocity at the lateral mitral annulus. 2D-Doppler measurements were re-assessed in LVSD patients 4 ± 2 months after cardiac resynchronization therapy (CRT).
IACT was longer in LVSD patients compared to NC (105±25 vs. 74±12 ms, p <.001);none of the NC had IACT> 100ms.In LVSD patients, IACT correlated modestly with measurements of LA volumes (r =.41-.48, all p <.009) but not with measurements of LA function. LVSD patients with IACT > 100 ms (n=20) prior to CRT had larger LA volumes and lower indices of LA function after CRT compared to the ≤ 100ms group. Significant reductions in LV end-systolic volume and increases in LV ejection fraction occurred in both groups after CRT.
TDI-derived IACT can be prolonged in patients with severe LVSD and a wide QRS interval. An IACT > 100 ms. can affect LA remodeling and function at early follow-up after CRT but does not influence the response in LV end-systolic volume or ejection fraction.
PMCID: PMC2684572  PMID: 19345063
interatrial conduction time; left ventricular systolic dysfunction; left atrial function; cardiac resynchronization therapy
5.  Relation of Serum Fetuin-A Levels to Coronary Artery Calcium in African-American Patients on Chronic Hemodialysis 
Vascular calcium deposition in end-stage renal disease occurs commonly, however its relationship to cardiovascular risk factors and fetuin-A levels in African-Americans is not known. Compliant African-American HD patients (n=17) agreed to undergo a 64-slice multidetector computed tomography for the assessment of coronary artery calcium score (CACS). The relationship between traditional cardiovascular risk factors (i.e., age, gender, dialysis vintage, history of diabetes, means of the previous 3 years of the weekly pre-dialysis blood pressure and hemoglobin, means of monthly values of calcium, phosphorus, alkaline phosphatase, uric acid and albumin, and means of quarterly measures of parathyroid hormone and lipids), and fetuin-A levels and CACS was explored by univariate analyses. Serum phosphorus levels over the previous 3 years were well controlled. The CACS range was 0-3,877 Agatston units (mean: 996; median :196). Among the tested variables, only fetuin-A was significantly and inversely associated with CACS (standardized β = -0.64 [95% confidence limits [CL]: -18.09, -3.62], p=0.006). There was no association between age and fetuin-A level (standardized β = -0.02 [95%CL: -0.10, 0.23]). In conclusion, African-American patients on long-term HD and with good phosphorus control exhibit a strong inverse correlation between fetuin-A levels and CACS which is independent of age.
PMCID: PMC2631229  PMID: 19101228
Fetuin-A; Hemodialysis; Coronary artery calcium score; African-American

Results 1-5 (5)