Upload
jocelyn-parker
View
231
Download
3
Tags:
Embed Size (px)
Citation preview
Essentials of CHF
Comorbidities and outcomes in CHF
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
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
0 20 40 60Patients (%)
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
ADHERE (n=107,920)
EURO HF (n=11,327)
OPTIMIZE-HF (n=34,059)
Mean age (y) 75 71 73
Women (%) 52 47 52
Prior HF (%) 75 65 87
LVEF <40% 51 46 52
Coronary artery disease (%) 57 68 50
Hypertension (%) 72 53 71
Diabetes (%) 44 27 42
Atrial fibrillation (%) 31 43 31
Renal insufficiency (%) 30 18 NA
Fonarow GC. Am Heart J 2008;155:200−207
Demographics and Concomitant Diseases of Hospitalised Patients with HF in Registries
NA=not available
Cardiovascular Health Study: 5808 subjects, aged >65 years, follow-up: 7.3 years2
Association between Renal Function and CV Outcomes
Fried LF et al. J Am Coll Cardiol 2003;41:1364−1372
1.0
2.0
<1.10 1.10−1.29 1.30−1.49 1.50−1.69 1.70
Serum creatinine mg/dL
Hazard ratio and 95% CI for CVD
Hazard ratio and 95% CI for CHF
48%
92%
Hazard
rati
o
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;41:725−728
20%
40%
60%
GFR<6021%
SOLVD-PNYHA I–II
(n=3673)1
SOLVD-TNYHA II–III(n=2161)1
VALIANT(post AMI, CHF / LVD)
(n=14,527)2
34%
62%
Clinical trials (patients with severe RD excluded)
GFR<6036% GFR
60−75GFR
45−60
GFR<45 GFR
>90
GFR60−90
GFR30−59
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;35:681−689 2. Anavekar NS et al. N Engl J Med 2004;351:1285−1295
3. Heywood JT et al. J Card Fail 2007;13:422−430
% o
f p
ati
en
ts w
ith
ren
al d
ysfu
ncti
on
GFR, glomerular filtration rate
Ljungman S et al. Drugs 1990;39(Suppl 4):10−21
0
15
20
25
30
35
FF (
%)
0
1.2 1.6 2.0 2.4
Cardiac Index (L/min/m2)
20
40
60
80
GFR
(m
L/m
in/1
.73
m2)
0
100
200
300
400
500
RB
F (
mL/m
in/1
.73
m2)
GFR
FF
RBF
CHF Impairs Renal Function
RBF=renal blood flowFF=filtration fraction
Hillege HL et al. Circulation 2000;102:203−210
RR
(fo
r m
ort
ality
)
1.0
3.0
2.0
GFR
>76 59–76 44–58 <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
0 250 500 750 1000 12500.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Days
59−76 mL/min
44−58 mL/min
<44 mL/min
>76 mL/min
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. O’Meara E et al. Circulation 2006;113:986−94
Prevalence of Anaemia in CHF: Clinical Trials
Anaemia (Hb<12 g/dL) Occurs Early in CHF Progression
Pati
en
ts (
%)
Silverberg DS. J Am Col Cardiol 2000;35:1737–44
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
Anaemia in CHF Adversely Affects Outcomes (2/2)
O’Meara E et al. Circulation 2006;113:986−94
Patients with anaemia
Patients without anaemia
Mortality
50
100
150
Per
1000 p
ati
en
t-years
CV Non-CV
Reduced LVEF Preserved LVEF
CV Non-CV
Hospital admissions
100
200
400
Per
1000 p
ati
en
t-years
CV Non-CV
Reduced LVEF Preserved LVEF
CV Non-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
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
2.5RR 0.986p<0.001
RR 1.033p<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
Low High
ELITE II – RR for death during follow-up (n=3044)
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 anticoagulationRenal failure
- Reduced EPO productionMedication
- Use of ACE-inhibitors
Haemodilution
Functional ID - Vitamin B12, folate
Absolute ID
- Chronic blood loss- Malabsorption
Pathophysiology of Anaemia in CHF: Possible Aetiologies
Anaemia, CHF and CKD have an Additive Effect on Mortality
Anaemia can increase disease progression, hospitalisation, morbidity, and mortality, in patients with CHF1–3 and with CKD4–8
There is an additive effect of each of anaemia, CKD and CHF affecting mortality risk6,9,10 and progression to ESRD9,10
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
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 CKI 7.7 0.1
Anaemia 16.6 0.1
CHF 26.1 0.2
CHF and anaemia 34.6 0.3
CKI 16.4 2.6
CKI and anaemia 27.3 5.4
CHF and CKI 38.4 3.5
CHF, CKI and anaemia 45.6 5.9
Note: the additive effect of anaemia, CHF and CKI on the mortality rate and on the incidence of ESRD
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
Pre
dic
ted
pro
bab
ilit
y
of
in-h
osp
ital d
eath
Admission Hb (5–20 g/dL)
4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
1,136,201 patients in the 5% Medicare database
– anaemia, CKD and CHF contribute significantly to mortality rates
34.6
CHF andanaemia
Patients with CRAS have a 2-year Mortality Rate of ~46%
0
10
20
30
40
50
7.7
Noanaemia
CHF or CKI
16.1
Anaemia
26.6
CHF
27.3
CKI andanaemia
38.4
CHF andCKI
45.6
Anaemia,CHF and
CKI
2-y
ear
mort
ality
(%
)
Silverberg D et al. Nephrol Dial Transplant 2003;18(suppl 8):viii7–viii12
16.4
CKI
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
CKI0
2
4
6
5.4
CKI and
anaemia
3.5
CHF and CKI
5.9
Anaemia,CHF and
CKI
2-y
ear
incid
en
ce o
f ES
RD
(%
)
No anaemia,CHF or
CKI
0.1
Anaemia
0.2
CHF
0.2
CHF and anaemia
0.3
The Prognostic Value of Anaemiain Patients with Diastolic Heart Failure
Tehrani F et al. Texas Heart J 2009;36:220–225
0
0
Su
rviv
al d
istr
ibu
tion
fu
ncti
on
(%
)
10
Survival time (months)
0.2
0.6
0.4
0.8
1.0
20 30 40 50 60 70
No anaemia (n=132)
Anaemia (n=162)
Anaemia in Diastolic HF
Felker GM et al. Am Heart J 2006;151:457–462
0.3
0.1
0
0
Su
rviv
al p
rob
ab
ilit
y
1
Years
2 3 4 5 6 7
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
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 years1
1. Go AS et al. N Engl J Med 2004;351:1296–1305
Ag
e-s
tan
dard
ised
rate
of
death
fro
m a
ny c
au
se
(per
100
pers
on
years
)
0.76
≥60
1.08
45–59 30–44 15–29 <15
eGFR (mL/min/1.73 m2)
15
10
5
0
Mortality (N=51,424)
Ag
e-s
tan
dard
ised
rate
of
CV
even
ts
(per
100
pers
on
years
)
2.11
≥60
3.65
45–59 30–44 15–29 <15
eGFR (mL/min/1.73 m2)
40
20
0
CV events (N=138,291)
Hospitalisation (N=554,651)
Ag
e-s
tan
dard
ised
rate
of
hosp
italisati
on
(p
er
100
pers
on
years
)
13.54
≥60
17.22
45–59 30–44 15–29 <15
eGFR (mL/min/1.73 m2)
150
100
50
0
30
1011.29
21.80
36.60
4.76
11.36
14.14
42.26
86.75
144.61
Rapid Declines in Kidney Function* are Associated with Greater Incidence of CV Events
Cohort of 4378 patients aged ≥65 years recruited from Medicare eligibility lists1
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;20:2625–2630MI, myocardial infarction; PAD, peripheral arterial disease
*defined as cystatin C-based eGFR >3 mL/min/1.73 m2/year
CV Morbidity and Mortality Increase with Worsening Kidney Function
CKD progression leads to a requirement for dialysis and/or kidney transplantation1
However, most patients with CKD die prematurely of CVD2
– CV morbidity and mortality increases with decreasing kidney function3–5
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
Juenger J et al. Heart 2002;87:235–41
CHF: Impact on QoL Compared with Other Diseases
SF-3
6 s
core
* (%
)
n=906 n=502 n=70 n=120 n=205
* General health perceptions
Juenger J et al. Heart 2002;87:235–41
QoL in Relation to NYHA ClassSF-
36 s
core
* (%
)
n=906 n=24 n=98 n=83
* General health perceptions
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
Pati
en
ts (
%)
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