Angela Yee-Moon Wang, MD, PhD Department of Medicine Queen Mary - PowerPoint PPT Presentation

Angela Yee-Moon Wang, MD, PhD Department of Medicine Queen Mary Hospital University of Hong Kong Hong Kong

Disclosures  Received Speaker Honorarium from Genzyme, Roche Diagnostics and Baxter Corporation.  Received grants from Baxter, Genzyme and Abbott Laboratory.  Advisory Board for Genzyme Asia.  Medical advisory board for Baxter Extramural Grant Program.

Prevalence of Heart Failure in Dialysis Population Author, year HD/PD N I or P Prevalence Harnett, 1999 HD + PD 432 I 31 Stack, 2001 HD + PD 4024 I 36 Wang, 2002 PD 246 P 38 Cheung, 2004 HD 1846 P 40 Couchard, 2008 PD 1530 I 34 HD 9285 I 28 Moretti, 2008 PD 298 P 9.9 I, incident; P, prevalent; HD, hemodialysis; PD, peritoneal dialysis; N, number

Heart Failure Increased Risk of Early Death (within 90 days of Dialysis Initiation) in Dialysis Patients Factor Level OR (95% CI) Age 45-64 2.1 (1.4, 3.3) 4.3 (2.8, 6.6) 65-74 75+ 5.0 (3.2, 7.8) Gender Male 1.6 (1.3, 1.9) Albumin (g/L) 35-40 1.4 (0.9, 2.2) 31-34 2.4 (1.5, 3.7) 10-30 4.4 (2.8, 6.9) Heart failure Yes 1.5 (1.2, 1.9) 8.8 (4.2, 18.6) Myocardial infarction by age level <45 45-64 1.4 (0.8, 2.4) 65-74 1.2 (0.8, 1.9) 75+ 1.0 (0.6, 1.6) Hypertension Yes 0.7 (0.6, 0.9) Smoking Yes 1.3 (1.0, 1.7) Activity impairment Severe 2.3 (1.4, 3.6) Soucie JM, et al. J Am Soc Nephrol 1996

Baseline History of Heart Failure Increased Long Term Mortality Risk in Dialysis Patients Harnett JD, et al. Kidney Int 1995

Background Heart Failure Increases Risk of Mortality and Heart Failure in PD Patients Wang AY, et al. Clin J Am Soc Nephrol 2011

Prevalence of De-novo or Recurrent Heart Failure in Relation to Baseline Heart Status in Dialysis Patients PD patients HD + PD patients 61.6% 56% 27.6% 25% Wang AY, et al. J Am Soc Nephrol 2007 Harnett JD, et al. Kidney Int 1995

Factors Predicting Heart Failure in PD Patients P HR (95% CI) Hemoglobin (1 g/dl ↑ ) 0.064 0.87 (0.76, 1.01) Serum albumin (1 g/L ↑ ) 0.014 0.94 (0.89, 0.99) Diabetes mellitus 0.115 1.46 (0.91, 2.35) Systolic blood pressure (1 mmHg ↑ ) < 0.001 1.03 (1.01, 1.04) Atherosclerotic vascular disease 0.026 1.75 (1.07, 2.87) LV mass index (1 g/m 2.7 ↑ ) 0.050 1.006 (1.000, 1.011) Ejection fraction (1 % ↑ ) 0.014 0.97 (0.94, 0.99) Wang AY, et al. Kidney Int 2006

Factors Predicting New Onset and Recurrent Heart Failure in PD Patients Over A 4-year Prospective Follow-up Factors Hazard ratios (95% P -value confidence intervals) New onset heart failure - Diabetes mellitus 2.93 (1.46 – 5.87) 0.002 LV mass index (g/m 2 ) 1.005 (1.000 – 1.010) 0.070 LV volume index (ml/m 2 ) 1.027 (1.004 – 1.050) 0.019 Recurrent heart failure - Serum albumin (g/L) 0.91 (0.86 – 0.97) 0.002 Systolic blood pressure (mmHg) 1.04 (1.02 – 1.06) <0.001 LV volume index (ml/m 2 ) 1.012 (1.001 – 1.024) 0.03 Wang AY, et al. Clin J Am Soc Nephrol 2011

Prevalence of LV Hypertrophy and Cardiac Dysfunction in Dialysis Patients Author, yr HD or PD I or P No. Prevalence Prevalence of of LVH (%) Systolic Dysfunction (%) Greaves 1994 HD + PD P 84 NS 36 (FS ≤ 25%) Foley 1996 HD + PD I 432 74 18 (FS ≤ 25%) Mallamaci HD + PD P 254 77 22 (EF ≤ 45%) 2000 Wang 2006 PD P 246 95 33 (EF < 50%) HD, hemodialysis; PD, peritoneal dialysis; P, prevalent; I, incident; LVH, left ventricular hypertrophy, FS, fractional shortening, EF, ejection fraction; NS, not stated.

Systolic ¡Dysfunc.on ¡Predicts ¡Sudden ¡Cardiac ¡Death ¡in ¡ ESRD ¡Pa.ents ¡ cTnT ≤ 0.01 µ g/L cTnT between 0.01 – 0.99 µ g/L cTnT ≥ 0.1 µ g/L P=0.001 Wang AY, et al. Hypertension 2010

Cardiac Hypertrophy and Dilatation

Myocyte Capillary Mismatch in the Heart of Uremic Patients control Essential HT CRF patient Amann K, et al. J Am Soc Nephrol 1998

Cardiac Pathology in Hemodialysis Patients with Dilated Cardiomyopathy Aoki, et al. Kidney Int 2005

Factors Predicting Heart Failure in Multivariable Cox Regression Model P=0.038 P=0.017 P=0.02 Model 1 + Model 2 + Model 3 + Hb, SAlb, LVM index LV EF cardiac DM, SBP troponin T and background AVD Models Wang AY, et al. Kidney Int 2006

Cardiac Troponin T Enhances the Predictive Value of Systolic Dysfunction and LV Hypertrophy for Heart failure in PD Patients P Adjusted HR* 95% CI TnT > 0.06 µ g/L, LV EF > 50% 0.034 1.88 1.05, 3.38 TnT ≤ 0.06 µ g/L, LV EF ≤ 50% 0.398 1.42 0.63, 3.19 TnT > 0.06 µ g/L, LV EF ≤ 50% <0.001 3.10 1.71, 5.63 Vs ref group : TnT ≤ median (0.06 µ g/L), LV EF > 50% P Adjusted HR** 95% CI TnT > 0.06 µ g/L, LVMi < median 0.097 1.91 0.89, 4.10 TnT ≤ 0.06 µ g/L, LVMi ≥ median 0.148 1.72 0.83, 3.58 TnT >0.06 µ g/L, LVMi ≥ median 0.003 2.68 1.39, 5.19 Vs ref group : TnT ≤ median (0.06 µ g/L), LVMi < median Adjusting for SBP, atherosclerotic vascular disease, Wang AY, et al. Kidney Int 2006 hemoglobin, serum albumin, *LV mass index and **LV EF.

Risk Factors for Left Ventricular Hypertrophy Extra-cellular Hypertension Inflammation volume expansion Anemia Arterial stiffening Sympathetic Renin-angiotensin Overactivity system Left Diabetes ventricular Uremic milieu Old Age hypertrophy Abnormal calcium*phosphorus Hypoalbumin metabolism Asymmetric dimethyl arginine Hyperparathyroidism Local growth Vitamin D factors deficiency Myocardial ischemia

Effect of Sodium and Fluid Removal on Survival of Peritoneal Dialysis Patients Sodium Removal (mmol/24 h/ Fluid Removal (mL/24 h/1.73 m 2 ) 1.73 m 2 ) - - group I, <130 group I, <1265 group II, 130 to 181 group II, 1265 to 1570 group III, 181 to 232 group III, 1570 to 2035 group IV, > 232 group IV, > 2035 Ates K, et al. Kidney Int 2001

Worse Echocardiographic Measures in PD Patients with History of Volume Overload History of volume No history of volume P overload (N=98) overload (N=152) LV mass index (g/m 2 ) 262 ± 89 205 ± 75 <0.001 LV end diastolic diameter (cm) 5.29 ± 0.82 4.84 ± 0.79 <0.001 LV end systolic diameter (cm) 3.70 ± 0.93 3.16 ± 0.76 <0.001 LV ejection fraction 0.65 ± 0.13 0.71 ± 0.11 <0.001 LV fractional shortening 0.31 ± 0.09 0.35 ± 0.08 <0.001 Diastolic Function (%) - Normal 22 21 0.001 - Abnormal relaxation pattern 61 77 Pseudo-normal 1 0 - - Restrictive filling pattern 16 2 Wang AY, et al. Am J Clin Nutr 2003

NT-pro-BNP – A Powerful Predictor of Heart Failure in PD Patients 1st Quartile 2nd Quartile 3rd Quartile Variable Adjusted hazard ratios P-value Quartile NT-pro-BNP level (95% confidence intervals) 4th Quartile 1 st ≤ 1927 pg/ml Diabetes 1.87 (1.19, 2.92) 0.006 2 nd ≥ 1928 - 5667 pg/ml Systolic blood pressure (1 mmHg) 1.02 (1.01, 1.04) 0.001 Coronary artery disease 1.68 (1.02, 2.76) 3 rd ≥ 5668 - 17533 pg/ml 0.041 P<0.001 NT-pro-BNP 4 th ≥ 17534 pg/ml - 2 nd Quartile versus 1 st Quartile 1.98 (0.85, 4.63) 0.114 - 3 rd Quartile versus 1 st Quartile 2.30 (1.00, 5.32) 0.050 - 4 th Quartile versus 1 st Quartile 7.17 (3.22, 15.99) <0.001 Wang AY, et al. J Am Soc Nephrol 2007

Extra-Cellular Volume Determined by Bromide Dilution in relation to Residual GFR Konings CJ, et al. Nephrol Dial Transplant 2003

Association between Residual Renal Function and Cardiac Hypertrophy in Peritoneal Dialysis Patients P=0.001 P=0.001 P=0.86 Wang AY, et al. Kidney Int 2002

Left Ventricular Filling Pressure (as Denoted by E/E’ ratio) is Inversely Associated with Residual Renal Function and Predicts Mortality in PD Patients Factors Unit ↑ OR 95% CI P LV volume index 1ml/m 2 1.06 1.04 - 1.09 <0.001 Residual GFR 1ml/min per 1.73m 2 0.76 0.62 - 0.93 0.009 Age 1 yr 1.05 1.02 - 1.08 0.002 LV ejection fraction 1% 0.94 0.88 - 0.99 0.026 Diabetes mellitus .. 2.06 0.94 – 4.50 0.071 E/E’, ratio of early transmitral inflow velocity to early diastolic mitral annular velocity Wang AY, et al. Hypertension 2008

Incremental Value of E/Em ratio (a non-invasive marker of Left Ventricular Filling Pressure) in Predicting Long- Term Outcomes of PD Patients Wang AY, et al. Hypertension 2008

Cardio-Renal Link in PD Patients ↑ Uremic milieu and middle Hyperphosphatemia Extracellular volume molecule uremic toxins overload 25(OH)D deficiency Hypoalbuminemia Anemia Inflammation Loss of Residual Renal Resting Function hypermetabolism ↑ Oxidative Stress Accelerated Cardiac hypertrophy & Valvular/vascular atherosclerosis dilatation calcification Systolic & diastolic Malnutrition Arterial stiffening dysfunction ↑ Overall Mortality and Cardiovascular Death Wang AY, et al. Kidney Int 2006

Progression to Heart Failure in ESRD Traditional Framingham Kidney disease-related risk factors risk factors LV hypertrophy Coronary ischemia ? Immune activation Non-immune factors Hemodynamic factors Neurohumoral activation Metabolic factors RAS activation LV remodeling Progressive LV dilatation Acute Chronic Heart Failure

Levine B, et al. N Engl J Med 1990

Tumor Necrosis Factor and the Failing Heart Yokoyama T, et al. J Clin Invest 1993

LV Remodeling and Collagen Content in a Transgenic Mouse Model with Targeted TNF Over-expression Mann DL, et al. Circ Res 2002