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Essentials of CHF Comorbidities and outcomes in CHF.

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Presentation on theme: "Essentials of CHF Comorbidities and outcomes in CHF."— Presentation transcript:

1 Essentials of CHF Comorbidities and outcomes in CHF

2 Anaemia and CHF Prevalence of anaemia in CHF: 1 – varies substantially by grade: less symptomatic 4–23% higher severity grade: 30–61% Incidence of anaemia in CHF: – SOLVD: 2 1 year: 9.6% – Val-HeFT: 3 1 year: 16.9% – COMET: 4 1 year: 14.2% 5 year: 27.5% 1. Tang YD et al. Circulation 2006;113:2454–61; 2. Ishani A et al. J Am Coll Cardiol 2005;45:391–9; 3. Anand IS et al. Circulation 2005;112:1121–7; 4. Komajda M et al. Eur Heart J 2006;27:1440–6

3 Prevalence of Anaemia in CHF: Registry Analyses 1. Cleland JG et al. Eur Heart J 2003;24:442–63; 2. Komajda M et al. Eur Heart J 2003;24:464–74; 3. Adams KF et al. Am Heart J 2005;149: 209–16; 4. Maggioni AP et al. J Card Fail 2005;11:91–8; 5. Horwich TB et al. J Am Coll Cardiol 2002;39:1780–6; 6. Silverberg DS et al. J Am Coll Cardiol 2000;35:1737–44; 7. McClellan W et al. Curr Med Res Opin 2004;20:1501–10; 8. van Tellingen A et al. Neth J Med 2001;59:270–9; 9. Ezekowitz JA et al. Circulation 2003;107:223–5 Patients (%) EHFS-I (Hb <12 g/dL) 1 EHFS-II (Hb <12 g/dL) 2 ADHERE (Hb <12 g/dL) 3 In-CHF (Hb <12 d/dLm, <11 w) 4 Horwich (Hb <12.3 g/dL) 5 Silverberg (Hb <12 g/dL) 6 McClellan (Hct <35%) 7 Golden (Hct <35%) 8 Alberta (ICD-9 codes) 9

4 ADHERE (n=107,920) EURO HF (n=11,327) OPTIMIZE-HF (n=34,059) Mean age (y) 757173 Women (%) 524752 Prior HF (%) 756587 LVEF <40% 514652 Coronary artery disease (%) 576850 Hypertension (%) 725371 Diabetes (%) 442742 Atrial fibrillation (%) 314331 Renal insufficiency (%) 3018NA Fonarow GC. Am Heart J 2008;155:200207 Demographics and Concomitant Diseases of Hospitalised Patients with HF in Registries NA=not available

5 Cardiovascular Health Study: 5808 subjects, aged >65 years, follow-up: 7.3 years 2 Association between Renal Function and CV Outcomes Fried LF et al. J Am Coll Cardiol 2003;41:13641372 1.0 2.0 <1.101.101.291.301.491.501.69 1.70 Serum creatinine mg/dL Hazard ratio and 95% CI for CVD Hazard ratio and 95% CI for CHF 48% 92% Hazard ratio

6 CV Risk: Influences on Renal Dysfunction Excess comorbidities Underuse of cardioprotective therapies Excess toxicities of therapies Abnormal CV biology – RAAS and SNS, proinflammatory activation, oxidative stress, LVH, impaired myocyte contractility) McCullough PA. J Am Coll Cardiol 2003;41:725728

7 20% 40% 60% GFR <60 21% SOLVD-P NYHA I–II (n=3673) 1 SOLVD-T NYHA II–III (n=2161) 1 VALIANT (post AMI, CHF / LVD) (n=14,527) 2 34% 62% Clinical trials (patients with severe RD excluded) GFR <60 36% GFR 6075 GFR 4560 GFR <45 GFR >90 GFR 6090 GFR 3059 GFR <30 ADHERE (acute, decompensated HF) (n=118,465) 3 Real life Renal Dysfunction – a Frequent Comorbidity in CHF 1.Dries DL et al. J Am Coll Cardiol 2000;35:681689 2. Anavekar NS et al. N Engl J Med 2004;351:12851295 3. Heywood JT et al. J Card Fail 2007;13:422430 % of patients with renal dysfunction GFR, glomerular filtration rate

8 Ljungman S et al. Drugs 1990;39(Suppl 4):1021 0 15 20 25 30 35 FF (%) 0 1.2 1.62.02.4 Cardiac Index (L/min/m 2 ) 20 40 60 80 GFR (mL/min/1.73 m 2 ) 0 100 200 300 400 500 RBF (mL/min/1.73 m 2 ) GFR FF RBF CHF Impairs Renal Function RBF=renal blood flow FF=filtration fraction

9 Hillege HL et al. Circulation 2000;102:203210 RR (for mortality) 1.0 3.0 2.0 GFR >76 59–7644–58 <44 1.91 2.85 1.32 1708 CHF patients (NYHA III–IV) from PRIME II Trial GFR was the most predictive of survival at multivariate analysis GFR <60 mL/min, 2.1 risk of mortality Surpassed LVEF, NYHA class, hypotension concomitant medications, diabetes mellitus, tachycardia Renal Dysfunction – A Strong Predictor of Poor Outcome in HF 025050075010001250 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Proportion Survival Days 5976 mL/min 4458 mL/min <44 mL/min >76 mL/min

10 Patients (%) ValHeFT (Hb <12 g.dL m 11 w) 1,2 ELITE-II (Hb <12.5 g/dL) 3 Renaissance (Hb <12 g/dL) 4 COMET men (Hb <13 g/dL) 5 COMET women (Hb <12 g/dL) 5 CHARM (Hb <12 g/dLw, 13 m) 6 1.Cohn JN et al. N Engl J Med 2001;345:1667–75; 2. Anand IS et al. Circulation 2005;112:1121–7; 3. Sharma R et al. Eur Heart J 2004;25:1021–8; 4. Anand I et al. Circulation 2004;110:149–54; 5. Komajda M et al. Eur Heart J 2006;27:1440–6; 6. OMeara E et al. Circulation 2006;113:98694 Prevalence of Anaemia in CHF: Clinical Trials

11 Anaemia (Hb<12 g/dL) Occurs Early in CHF Progression Patients (%) Silverberg DS. J Am Col Cardiol 2000;35:1737–44

12 Anaemia in CHF Adversely Affects Outcomes (1/2) Anaemia is an independent risk factor for mortality – in a meta-analysis of 34 studies involving a total of 153,180 patients with HF, 37% were anaemic – minimum 6-month mortality rates 46.8% among patients with anaemia 29.5% among patients without anaemia OR for increased death in the anaemic group: 1.96 (95% CI: 1.74, 2.21) – anaemia was an independent risk factor for mortality hazard ratio adjusted for anaemia: 1.46 (95% CI: 1.26, 1.69) Groenveld HF et al. J Am Coll Cardiol 2008;52:818–27

13 Anaemia in CHF Adversely Affects Outcomes (2/2) OMeara E et al. Circulation 2006;113:98694 Patients with anaemia Patients without anaemia Mortality 50 100 150 Per 1000 patient-years CVNon-CV Reduced LVEF Preserved LVEF CVNon-CV Hospital admissions 100 200 400 Per 1000 patient-years CVNon-CV Reduced LVEF Preserved LVEF CVNon-CV 300 CHARM study data Anaemia was associated with an increased risk of hospitalisation and death, a relationship observed in patients with both reduced and preserved LVEF

14 Sharma R et al. Eur Heart J 2004;25:1021–8 Non-linear Relationship Between Hb Levels and Mortality in CHF 3.0 2.0 1.5 1.0 0.5 0 2.5 RR 0.986 p<0.001 RR 1.033 p<0.001 Hb (g/dL) 11.5– 12.4 10.5– 11.4 8.0– 10.4 12.5– 13.4 13.5– 14.4 14.5– 15.4 15.5– 16.4 16.5– 17.4 17.5– 20.0 LowHigh ELITE II – RR for death during follow-up (n=3044)

15 van der Meer P et al. Eur Heart J 2004;25:285–91 Anaemia Malnutrition Chronic blood loss Bone marrow - Insensitivity to EPO - Cytokines (TNF-) - Chronic disease - Inflammation - Use of anticoagulation Renal failure - Reduced EPO production Medication - Use of ACE-inhibitors Haemodilution Functional ID - Vitamin B12, folate Absolute ID - Chronic blood loss - Malabsorption Pathophysiology of Anaemia in CHF: Possible Aetiologies

16 Anaemia, CHF and CKD have an Additive Effect on Mortality Anaemia can increase disease progression, hospitalisation, morbidity, and mortality, in patients with CHF 1–3 and with CKD 4–8 There is an additive effect of each of anaemia, CKD and CHF affecting mortality risk 6,9,10 and progression to ESRD 9,10 1. Vasu S et al. Clin Cardiol 2005;28:454–458; 2. He WS & Wang LX. Congest Heart Fail 2009;15:123–130; 3. Lindenfeld J. Am Heart J 2005;149:391–401; 4. Xia H et al. J Am Soc Nephrol 1999;10:1309–1316; 5. Levin A et al. Nephrol Dial Transplant 2003;18(suppl 4):358:393–394;6. Herzog CA et al. J Card Fail 2004;10:467–472; 7. Ma JZ et al. J Am Soc Nephrol 1999,10:610–619; 8. Thorp M et al. Nephrology 2009;14:240–246; 9. Efstratiadis G et al. Hippokratia 2008;12:11–16; 10. Silverberg D et al. Nephrol Dial Transplant 2003;18(suppl 8):viii7–viii12 ESRD, end-stage renal disease

17 CRAS – an Ominous Coexistence 2-year mortality and incidence of ESRD in a 5% sample of Medicare patients from the USA (1.1 million patients) Gilbertson D. J Am Soc Nephrol 2002;13:SA848 2-year mortality (%) 2-year incidence of ESRD (%) No anaemia, CHF or CKI7.70.1 Anaemia16.60.1 CHF26.10.2 CHF and anaemia34.60.3 CKI16.42.6 CKI and anaemia27.35.4 CHF and CKI38.43.5 CHF, CKI and anaemia 45.65.9 Note: the additive effect of anaemia, CHF and CKI on the mortality rate and on the incidence of ESRD

18 Relation of Hb levels to Mortality in Patients Hospitalized With HF (Insight from the OPTIMIZE-HF Registry) Young JB et al. Am J Cardiol 2008;101:223–230 0.11 0.10 0.09 0.08 0.07 0.06 0.05 0.04 0.03 0.02 0.01 0.10 Predicted probability of in-hospital death Admission Hb (5–20 g/dL) 456789101112131415161718192021

19 1,136,201 patients in the 5% Medicare database – anaemia, CKD and CHF contribute significantly to mortality rates 34.6 CHF and anaemia Patients with CRAS have a 2-year Mortality Rate of ~46% 0 10 20 30 40 50 7.7 No anaemia CHF or CKI 16.1 Anaemia 26.6 CHF 27.3 CKI and anaemia 38.4 CHF and CKI 45.6 Anaemia, CHF and CKI 2-year mortality (%) Silverberg D et al. Nephrol Dial Transplant 2003;18(suppl 8):viii7–viii12 16.4 CKI

20 Patients with CRAS have a 2-year ESRD Incidence Rate of ~6% 1,136,201 patients in the 5% Medicare database – anaemia, CKD and CHF contribute significantly to the incidence of ESRD Silverberg D et al. Nephrol Dial Transplant 2003;18(suppl 8):viii7–viii12 2.6 CKI 0 2 4 6 5.4 CKI and anaemia 3.5 CHF and CKI 5.9 Anaemia, CHF and CKI 2-year incidence of ESRD (%) No anaemia, CHF or CKI 0.1 Anaemia 0.2 CHF 0.2 CHF and anaemia 0.3

21 The Prognostic Value of Anaemia in Patients with Diastolic Heart Failure Tehrani F et al. Texas Heart J 2009;36:220–225 0 0 Survival distribution function (%) 10 Survival time (months) 0.2 0.6 0.4 0.8 1.0 203040506070 No anaemia (n=132) Anaemia (n=162)

22 Anaemia in Diastolic HF Felker GM et al. Am Heart J 2006;151:457–462 0.3 0.1 0 0 Survival probability 1 Years 234567 0.2 0.6 0.4 0.5 0.9 0.7 0.8 1 Anaemia/ISF No anaemia/PSF Anaemia/PSF No anaemia/ISF

23 KPRR=Kaiser Permanente Renal Registry;HR=hazard ratio Risk of CV Events and Hospitalisation Increases with Declining Kidney Function Cohort of 1,120,295 pre-dialysis patients from the KPRR studied for 2.84 years 1 1. Go AS et al. N Engl J Med 2004;351:1296–1305 Age-standardised rate of death from any cause (per 100 person years) 0.76 60 1.08 45–5930–4415–29<15 eGFR (mL/min/1.73 m 2 ) 15 10 5 0 Mortality (N=51,424) Age-standardised rate of CV events (per 100 person years) 2.11 60 3.65 45–5930–4415–29<15 eGFR (mL/min/1.73 m 2 ) 40 20 0 CV events (N=138,291) Hospitalisation (N=554,651) Age-standardised rate of hospitalisation (per 100 person years) 13.54 60 17.22 45–5930–4415–29<15 eGFR (mL/min/1.73 m 2 ) 150 100 50 0 30 10 11.29 21.80 36.60 4.76 11.36 14.14 42.26 86.75 144.61

24 Rapid Declines in Kidney Function* are Associated with Greater Incidence of CV Events Cohort of 4378 patients aged 65 years recruited from Medicare eligibility lists 1 Incidence of CV events was significantly higher in patients with rapid declines in kidney function (p<0.001) 1 Rapid declines in kidney function were independently associated with higher risk for heart failure, MI and PAD but not stroke 1. Shlipak MG et al. J Am Soc Nephrol 2009;20:2625–2630 MI, myocardial infarction; PAD, peripheral arterial disease *defined as cystatin C-based eGFR >3 mL/min/1.73 m 2 /year

25 CV Morbidity and Mortality Increase with Worsening Kidney Function CKD progression leads to a requirement for dialysis and/or kidney transplantation 1 However, most patients with CKD die prematurely of CVD 2 – CV morbidity and mortality increases with decreasing kidney function 3–5 1. Zhang Q-L & Rothenbacher D. BMC Public Health 2008;8:117; 2. Besarab A et al. N Engl J Med 1998;339:584–590; 3. Go AS et al. N Engl J Med 2004;351:1296–1305; 4. Shlipak MG et al. JAMA 2005;293:1737–1745; 5. Keith DS et al. Arch Intern Med 2004;164:659–663

26 Juenger J et al. Heart 2002;87:235–41 CHF: Impact on QoL Compared with Other Diseases SF-36 score* (%) n=906 n=502 n=70 n=120 n=205 * General health perceptions

27 Juenger J et al. Heart 2002;87:235–41 QoL in Relation to NYHA Class SF-36 score* (%) n=906 n=24 n=98 n=83 * General health perceptions

28 CHF Patients Willing to Trade Length of Life for Better QoL Lewis EF et al. J Heart Lung transplant 2001;20:1016–24 Patients are more willing to trade their time for improved QoL when symptoms are poor Patients (%)

29 QoL as a CHF Management Target? CHF reduces QoL at least as much as other chronic medical conditions (e.g., diabetes, arthritis, chronic lung disease) Treatment in CHF focuses on symptomatic improvement preventing the transition of asymptomatic cardiac dysfunction to symptomatic CHF, modulating the progression of CHF and reducing mortality Despite some recent evidence of improved prognosis after first hospitalisation for heart failure, pharmacological treatment does not impressively improve the high morbidity and mortality rates associated with CHF Thus QoL is a worthwhile target for patients with CHF


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