ninth international symposium heart failure & co. rozzano 17-18 aprile 2009 session iv...
TRANSCRIPT
Ninth International Symposium
HEART FAILURE & Co.Rozzano 17-18 aprile 2009
Session IVSession IV
““Advanced Heart Failure Prognosis Guided Clinical Management:Advanced Heart Failure Prognosis Guided Clinical Management:
Definition and Clinical Impact”Definition and Clinical Impact”
Edoardo Gronda, MD, FESCEdoardo Gronda, MD, FESC
Clinical Cardiology Heart Failure UnitClinical Cardiology Heart Failure Unit
Cardiovascular DepartmentCardiovascular Department
IRCCS, Istituto Clinico HumanitasIRCCS, Istituto Clinico Humanitas
Rozzano (Milano)Rozzano (Milano)
Distribution of HF population byDistribution of HF population byACC/AHA staging ACC/AHA staging
B B 34%34%
Structural heart diseaseStructural heart diseaseLVH, MI, low LVEF, cardiac dilatation, valvular LVH, MI, low LVEF, cardiac dilatation, valvular
disease disease
C 11,8%C 11,8% Prior, current Prior, current
symptomssymptoms
DD0,2%0,2%
RefractoryRefractory
A A 22% 22%
High RiskHigh RiskHypertension, coronary disease, diabetes, renal disease, family history, etc.Hypertension, coronary disease, diabetes, renal disease, family history, etc.
Ammar et al Circulation 2007; 115: 1563Ammar et al Circulation 2007; 115: 1563
COMPANION(C) COMPANION(C) COMPANION(C) COMPANION(C)
bl 65%bl 65% bl 65%bl 65%
Class III / IVClass III / IV LVEF 23 %QRS 0,16”
HF-Hospital Adm> 1, < 12 mos
Class III / IVClass III / IV LVEF 23 %QRS 0,16”
HF-Hospital Adm> 1, < 12 mos
19%19%19%19%
T = treatment groupT = treatment groupC = control groupC = control groupT = treatment groupT = treatment groupC = control groupC = control group
% One Year Mortality% One Year Mortality% One Year Mortality% One Year Mortality
30303030
40404040
20202020
10101010
60606060
CRT-DCRT-D - 27%- 27%
1y 1y (14,5%)(14,5%)
CRT-DCRT-D - 27%- 27%
1y 1y (14,5%)(14,5%)
0000
70707070
************
COMPANION(C) COMPANION(C) COMPANION(C) COMPANION(C)
bl 52%bl 52% bl 52%bl 52%
Class IVClass IV LVEF 20,8%QRS 0,16”
HF-Hospital Adm> 1, < 12 mos
Class IVClass IV LVEF 20,8%QRS 0,16”
HF-Hospital Adm> 1, < 12 mos
44%44%44%44%
CRT-DCRT-D - 31%- 31%1y 1y (31%)(31%)
CRT-DCRT-D - 31%- 31%1y 1y (31%)(31%)
80808080
73%73%73%73%
INO 73%INO 73%INO 73%INO 73%
REMATCH ©REMATCH ©REMATCH ©REMATCH ©
Class IVClass IVend stageend stageClass IVClass IVend stageend stage
Refractory HFRefractory HF requiring requiring specialized specialized
interventions interventions (ACC/AHA Stage D)(ACC/AHA Stage D)
Refractory HFRefractory HF requiring requiring specialized specialized
interventions interventions (ACC/AHA Stage D)(ACC/AHA Stage D)
HF SEVERITYHF SEVERITYHF SEVERITYHF SEVERITY
MADIT II (C) MADIT II (C) MADIT II (C) MADIT II (C)
Class II / IVClass II / IVLVEFLVEF<<30%30% bl 70%bl 70%
Class II / IVClass II / IVLVEFLVEF<<30%30% bl 70%bl 70%
Class IVClass IV bl 100%bl 100%Class IVClass IV bl 100%bl 100%
Merit-HF(T)Merit-HF(T)CIBIS 1994 (T)CIBIS 1994 (T)CIBIS- II (T)CIBIS- II (T)
Merit-HF(T)Merit-HF(T)CIBIS 1994 (T)CIBIS 1994 (T)CIBIS- II (T)CIBIS- II (T)
11,6 - 14%11,6 - 14%11,6 - 14%11,6 - 14%
52% QRS >0,12”52% QRS >0,12”52% QRS >0,12”52% QRS >0,12”
Class IIIB / IVClass IIIB / IV
LVEF<25%LVEF<25%
Class IIIB / IVClass IIIB / IV
LVEF<25%LVEF<25%
COPERNICUS COPERNICUS Overall (T)Overall (T)
COPERNICUS COPERNICUS Overall (T)Overall (T)
RALES (T)RALES (T)RALES (T)RALES (T)
Class III / IVClass III / IVLVEF<35%LVEF<35%
Class III / IVClass III / IVLVEF<35%LVEF<35%
bl 11%bl 11% bl 11%bl 11%
18%18%18%18%
CONSENSUS (T) CONSENSUS (T) CONSENSUS (T) CONSENSUS (T)
Heart replacementHeart replacement
Advanced Heart Failure Defined Advanced Heart Failure Defined by:by:
1.1. Neurohormonal drugs failure Neurohormonal drugs failure –intolerance.–intolerance.
Ventricular Remodeling & Performance Ventricular Remodeling & Performance consequenceconsequence
Pre
ssu
re (m
m H
g)
Pre
ssu
re (m
m H
g)
Volume (ml)Volume (ml)
E.S.P.V.R
E.S.P.V.R
Kono et al. Am J Cardiol. 1991Kono et al. Am J Cardiol. 1991
Mitral Regurgitation in LV Systolic Mitral Regurgitation in LV Systolic DysfunctionDysfunction
Local LV remodeling Local LV remodeling (apical and posterior displacement of papillary muscles)(apical and posterior displacement of papillary muscles) leads to excess valvular tenting independent of global LV remodeling leads to excess valvular tenting independent of global LV remodeling
which, in turn, impacts global remodelling.which, in turn, impacts global remodelling.
posterior
apical
LV enlarges-loss of LV enlarges-loss of elliptical shape; more elliptical shape; more
sphericalspherical
Mitral annulus dilates
Papillary muscles displace
Chordae tether leaflets
Valve leaflets are not in coaptation…
Functional Functional Mitral Mitral
RegurgitationRegurgitation
Increased LV end Increased LV end diastolic pressurediastolic pressure
Functional MR begets MR in cardiomyopathy:Functional MR begets MR in cardiomyopathy:from local to global remodelling from local to global remodelling
SAVE Study: SAVE Study: Comparison of Ventriculographic Variables.Comparison of Ventriculographic Variables.
No MR (n=586)No MR (n=586)LV EF% LV EF% 3131++ 7 7
M R (n=141)M R (n=141)LV EF% LV EF% 32 32 ++ 7 7
P <P <
LV End DLV End D Vol. mlVol. ml
LV End SLV End S Vol. mlVol. ml
LV LV SphericitySphericity systolic %systolic %
Change%Change%
Lamas et al. Circulation 96:827 (97)Lamas et al. Circulation 96:827 (97)
202202 ++ 68 68
120120 ++ 47 47
3838 ++ 7 7
2828 ++ 7 7
99 ++ 6 6
239239 ++ 84 84
148148 ++ 65 65
4141 ++ 10 10
3434 ++ 11 11
77 ++ 7 7
.001.001 .001.001 .001.001 .001.001 .001.001
LV LV SphericitySphericity diastolic %diastolic %
SAVE Study: SAVE Study: Comparison of Survival on the basis of (mild) MRComparison of Survival on the basis of (mild) MR
Lamas et al., Lamas et al., CirculationCirculation 1997, 96: 827 1997, 96: 827
LVEF% 31+ 7
LVEF% 32 + 7
MR absent
MR present
Relationship between LV SIZE and VT Relationship between LV SIZE and VT
Sutton J et Al.Circulation 2003;
107:2577
Ventricular Shape and Function and Ventricular Shape and Function and Electric VulnerabilityElectric Vulnerability
Electrical Storm
NYHA f.cl. INYHA f.cl. I
Predicting the Long-Term effects of cardiac Predicting the Long-Term effects of cardiac resynchronization therapy on mortalityresynchronization therapy on mortality
Cleland J et al. J Am Coll Cardiol 2008Cleland J et al. J Am Coll Cardiol 2008
Predicting Causes of death in heart failurePredicting Causes of death in heart failureCARE HF post hoc analysisCARE HF post hoc analysis
Uretsky et al. J of Cardiac Fail 2008 Uretsky et al. J of Cardiac Fail 2008
IMR* 1,815 (1,765-2,602) .0012IMR* 1,815 (1,765-2,602) .0012
Advanced Heart Failure Defined Advanced Heart Failure Defined by:by:
1.1. Neurohormonal drugs failure Neurohormonal drugs failure –intolerance.–intolerance.
2.2. Ventricular remodelling leading Ventricular remodelling leading to mitral regurgitation and/or to mitral regurgitation and/or electric instability electric instability
dP/dT
diameter
By the La Place law : By the La Place law :
the energy the energy generationgeneration depends by ventricular depends by ventricular wall wall muscle thicknessmuscle thickness
the energy the energy transfer transfer into intracavitary blood into intracavitary blood (pressure(pressure) depends by ) depends by chamber curvature chamber curvature (zero curvature = no energy transfer).(zero curvature = no energy transfer).
Remodelling and dysfunction Remodelling and dysfunction
Heart and Kidney Heart and Kidney InteractionInteraction
Renal blood flow is maintained over a Renal blood flow is maintained over a wide range of blood pressures auto-wide range of blood pressures auto-regulating mechanisms.regulating mechanisms.
It does not fall until the mean arterial It does not fall until the mean arterial pressure falls below the critical level pressure falls below the critical level ((around 80mm Hgaround 80mm Hg).).
Sistemic Effect of CHFSistemic Effect of CHF
1. R.A.A.S.1. R.A.A.S. ActivationActivation2. Cathecolamine2. Cathecolamine secretionsecretion3. Vasopressin release3. Vasopressin release
Renal Renal UnderperfusionUnderperfusion
Renal fraction of cardiac output Renal fraction of cardiac output normally constitutes about 20% of normally constitutes about 20% of cardiac output.cardiac output.
With low cardiac output, blood is With low cardiac output, blood is shunted from the kidneys to shunted from the kidneys to heart and brain circulation: heart and brain circulation:
the renal fraction of cardiac output is the renal fraction of cardiac output is thereby lowered in a non proportional thereby lowered in a non proportional way.way.
Kidney perfusionKidney perfusionDemand Demand
Car
diac
Out
put
(L/m
in)
Left Ventricular Filling Pressure (mm Hg)
Normal
Heart Failure
Decreas
ed Renal
Function
Decreased
Congestion
0 15 30
5.0
2.5
0
Robert W. Schrier, MDCirc Heart Fail. 2008;1:2-5
Diuretic use may decrease Diuretic use may decrease cardiac outputcardiac output
and impair renal function.and impair renal function.The “Bill”The “Bill”
Lungs congestionLungs congestionusually occurs earlier thanusually occurs earlier thanSBL fall below 80 mm Hg SBL fall below 80 mm Hg
Diuretics and Mortality - PRAISE1Diuretics and Mortality - PRAISE1
0%
25%
50%
75%
100%
0 1 2 3
Years
Figure 2 -KM Survival - Daily Diuretic Dose mg/kg
4 mg/kg
3-4 mg/kg
2-3 mg/kg
1-2 mg/kg
0.5-1 mg/kg
<0.5 mg/kg
p<0.0001
Levy et al Circ 2006Levy et al Circ 2006
Advanced Heart Failure Defined Advanced Heart Failure Defined by:by:
1.1. Neurohormonal drugs failure –Neurohormonal drugs failure –intolerance.intolerance.
2.2. Progression of LV remodelling leading Progression of LV remodelling leading to mitral regurgitation to mitral regurgitation and/or electric and/or electric instability. instability.
3.3. Fluid retention indexed by diuretic Fluid retention indexed by diuretic need and declining Kidney function.need and declining Kidney function.
EchocardiographyEchocardiography
Mitral regurgitation leads leads to high LV end-diastolicto high LV end-diastolicpressure (ROA 0,22 cmpressure (ROA 0,22 cm22))
Restrictive filling patternRestrictive filling patternDrives increasing Pulmonary Artery Drives increasing Pulmonary Artery PressurePressure
Time to death, transplantation, or LVAD implantationTime to death, transplantation, or LVAD implantation in in
patients with patients with lowlow and and highhigh RV systolic pressureRV systolic pressureTedrow UB et al Am J Cardiol. 2006 Jun 15;97(12):1737-40 Tedrow UB et al Am J Cardiol. 2006 Jun 15;97(12):1737-40
Color Doppler:Color Doppler:
• Tricuspid RegurgitationTricuspid Regurgitation
• TAPSE 8TAPSE 8
• Right ventricular Right ventricular
impairment leads toimpairment leads to
progressiveprogressive
Venous congestionVenous congestion
EchocardiographyEchocardiography
Increased MyocardialIncreased MyocardialWall Stress and Wall Stress and EdomyocardialEdomyocardial
IschemiaIschemia
Increased MyocardialIncreased MyocardialWall Stress and Wall Stress and EdomyocardialEdomyocardial
IschemiaIschemia
Right Ventricular Right Ventricular Dilatation andDilatation andRemodelingRemodeling
Right Ventricular Right Ventricular Dilatation andDilatation andRemodelingRemodeling
Increased CardiacIncreased CardiacFillingFilling
PressurePressure
Increased CardiacIncreased CardiacFillingFilling
PressurePressure
Extracellular FluidExtracellular FluidVolume ExpansionVolume Expansion
Extracellular FluidExtracellular FluidVolume ExpansionVolume Expansion
Pulmonary Arterial Pulmonary Arterial Hypertension and Hypertension and Right Ventricular Right Ventricular
FailureFailure
Pulmonary Arterial Pulmonary Arterial Hypertension and Hypertension and Right Ventricular Right Ventricular
FailureFailure
TricuspidTricuspidRegurgitationRegurgitation
TricuspidTricuspidRegurgitationRegurgitation
Septal Shift andSeptal Shift andDecreased LeftDecreased LeftVentricular OutputVentricular Output
Septal Shift andSeptal Shift andDecreased LeftDecreased LeftVentricular OutputVentricular Output
1. R.A.A.S.1. R.A.A.S. ActivationActivation2. Cathecolamine2. Cathecolamine secretionsecretion3. Vasopressin release3. Vasopressin release
1. R.A.A.S.1. R.A.A.S. ActivationActivation2. Cathecolamine2. Cathecolamine secretionsecretion3. Vasopressin release3. Vasopressin release
Renal sodiumWater Retention
Renal sodiumWater Retention
Schrier RW. Clin J Am Soc Nephrol 2008;3:1223-37
Congestion and outcome Congestion and outcome
Damman K et al. J Am Coll Cardiol 2009;53:582–8
Damman K et al. ESC 2008
CIBIS II post hoc analysisCIBIS II post hoc analysisPatients # 2,557
Advanced Heart Failure Defined Advanced Heart Failure Defined by:by:
1.1. Neurohormonal drugs failure –intolerance.Neurohormonal drugs failure –intolerance.
2.2. Progression of LV remodelling leading to Progression of LV remodelling leading to mitral regurgitation mitral regurgitation and/or electric instability. and/or electric instability.
3.3. Fluid retention indexed by diuretic need and Fluid retention indexed by diuretic need and declining kidney function.declining kidney function.
4.4. Pulmonary hypertension leading to Pulmonary hypertension leading to progressive right ventricular dysfunction and progressive right ventricular dysfunction and venous congestionvenous congestion
p < .05
p < .05Raised Venous Pressure:
A direct cause of renal sodium retention
Effect of Increasing Central Venous Pressure on GFR in Dogs Effect of Increasing Central Venous Pressure on GFR in Dogs with Constant BPwith Constant BP
0.5
0.8
1.1
1.4
0 2 4 6 8 0 6.25 12 18.75 25 0 (Central Venous Pressure)
GF
R (
ml/m
in)
GF
R (
ml/m
in)
mm Hg
High CVP significantlyimpairs GFR
Firth et al Lancet 5/7/88
Impact of Venous Congestion on Impact of Venous Congestion on Glomerular Net Filtration PressureGlomerular Net Filtration Pressure
Jessup and Costanzo JACC 2009 Vol. 53, No. 7, 597–9
The net effect is a further decrease in urine flow rate!The net effect is a further decrease in urine flow rate!
14 mm Hg 14 mm Hg 4 mm Hg4 mm Hg
Tubular urea reabsorption and flow dependence of urea clearance.
The decreased distal fluid delivery will slow tubular flow in the collecting duct and enhance the flow-dependent urea reabsorption.
1401401201201001008080
6060
4040
2020
00
Cle
arn
ce m
l/m
in
Urine flow rate ( ml/min)121210108866442200
Inuline
Creatinine
urea
Change in BUN mg /dLChange in BUN mg /dL
UREA not EGFR predicts 60 days UREA not EGFR predicts 60 days mortality in AHF ptsmortality in AHF pts
OPTIME-CHF InvestigatorsCirc Heart Fail. 2008; 1: 25–33
II
IIII
IIIIII
IVIV
JVP>6 cm
67 %
67 %
69 %
78 %78 %P=0,02 P=0,02
significant rise in jugular significant rise in jugular venous pressure asvenous pressure asquartile BUN values rosequartile BUN values rose
significant rise in jugular significant rise in jugular venous pressure asvenous pressure asquartile BUN values rosequartile BUN values rose
Advanced Heart Failure Defined Advanced Heart Failure Defined by:by:
1.1. Neurohormonal drugs failure –intolerance.Neurohormonal drugs failure –intolerance.
2.2. Progression of LV remodelling leading to mitral Progression of LV remodelling leading to mitral regurgitation and/or electric instability. regurgitation and/or electric instability.
3.3. Fuid retention indexed by diuretic need and Fuid retention indexed by diuretic need and declining Kidney function.declining Kidney function.
4.4. Pulmonary hypertension leading to progressive right Pulmonary hypertension leading to progressive right ventricular dysfunction and venous congestionventricular dysfunction and venous congestion
5.5. Increasing venous congestion further impacting Increasing venous congestion further impacting renal failurerenal failure
LVDysfLVDysf
Hemodynamic Derangement and HF Mortality: Hemodynamic Derangement and HF Mortality: a Matter of Multi-Systems Failurea Matter of Multi-Systems Failure% %
deaths / ydeaths / y
ACC/ACC/AHAStagAHAStag
e Be B
ACC/ACC/AHAStagAHAStag
e Be B
HF SeverityHF SeverityHF SeverityHF Severity
ACC/AHAACC/AHAStage CStage C
ACC/AHAACC/AHAStage CStage C
SevereSevereAsymptomaticAsymptomaticAsymptomaticAsymptomatic MildMildMildMild ModerateModerateModerateModerate
LVDysfLVDysf
2020
00
4040
6060
8080
100100
LVDysfLVDysf
ACC/AHAACC/AHAStage DStage D
ACC/AHAACC/AHAStage DStage D
NE RELEASENE RELEASE
RAAS RAAS activationactivation
Liver function in End-stage HF
Centrilobular Necrosis Centrilobular Necrosis
Dual blood supply: 80% portal vein 20% hepatic arteryHaemodynamic failure: flow redistibution
Hypoperfusion small intestine Hypoxic damageHypoxic damage
= MOF – starter
Gut related Gram-movement:sepsi
(Systemic inflammatory response syndrome)
Intrahepatic cholestasis
(Pierro:seminar 2004)(Pierro:seminar 2004)
(Moore:J trauma 1994)(Moore:J trauma 1994)
(Crawford:Hepatology1998)
Centrilobular Necrosis (Wadia JHLT 2005)
LVDysfLVDysf
LVDysfLVDysf
Hemodynamic Derangement and HF Mortality: Hemodynamic Derangement and HF Mortality: a Matter of Multi-Systems Failurea Matter of Multi-Systems Failure% %
deaths / ydeaths / y
ACC/ACC/AHAStagAHAStag
e Be B
ACC/ACC/AHAStagAHAStag
e Be B
HF SeverityHF SeverityHF SeverityHF Severity
ACC/AHAACC/AHAStage CStage C
ACC/AHAACC/AHAStage CStage C
SevereSevereAsymptomaticAsymptomaticAsymptomaticAsymptomatic MildMildMildMild ModerateModerateModerateModerate
LVDysfLVDysf
Periphery
HypoxicHypoxicdamagedamage
2020
00
4040
6060
8080
100100
LVDysfLVDysf
Inflammatory Inflammatory response:response:
IL2,6IL2,6TNF TNF Cytochines = Cytochines = Tissue Tissue NecrosisNecrosis
End Stage End Stage
ACC/AHAACC/AHAStage DStage D
ACC/AHAACC/AHAStage DStage D
NE RELEASENE RELEASE
RAAS RAAS activationactivation