Transcript 25% 53 year old man admitted with weight gain and dyspnea

Chronic Heart Failure
When Should You be Worried?
James C. Fang, MD
Heart Failure, Transplantation, and Circulatory
Assistance Program
University Hospitals/Case Medical Center
Heart Failure
Progressive, incurable, and ultimately fatal
• Stage A At high risk for HF but no
structural heart disease
• Stage B Structural heart disease but
w/o signs or symptoms of HF
• Stage C Structural heart disease with
prior or current symptoms
• Stage D Refractory HF requiring
specialized interventions
Hunt et al., Circulation 2001;104:2996
• HTN, DM, CAD,
cardiotoxins
• LVH, LVSD, MI, asx
valve dz
• Sx LVSD or asx on Tx
• Recurrent hosp, need
for Tx/VAD
Heart Failure is Increasing
Baker, WH et al. Circulation, Feb 2006; 113: 799 - 805
And Heart Failure Mortality Remains High
Levy D et al. N Engl J Med 2002;347:1397-1402
Mortality in
End-Stage Heart Failure
One-year survival rates





AIDS: 90%
Leukemia: 64%
Lung cancer: 42%
Pancreatic cancer: 21%
End-stage heart failure with optimum medical management:
25%
• 53 year old man admitted with weight gain and dyspnea
despite increasing loop diuretics
–
–
–
–
Third admission this year
Idiopathic CMP (EF 25%)
PAF w/ inappropriate ICD shocks
CRT 6 months prior
• Meds: carvedilol, digoxin, torsemide, aldactone, coumadin
– No ACEI/ARB because of worsening renal function
• BP 100/80, HR 85, R 22, JVD to jaw, clear lungs, S3, TR, MR,
loud P2, palp liver edge, distended abd, no edema
• Hct 30%, Na 130, BUN 55, Cr 2.5, EKG afib, QRS 130 msec
HF hospitalization is ominous
Risk of death increases three-fold after
HF hospitalization
Solomon SD, et al. Circulation 2007;116:1482-1487
• 53 year old man admitted with weight gain and dyspnea
despite increasing loop diuretics
–
–
–
–
Third admission this year
Idiopathic CMP (EF 25%)
PAF w/ inappropriate ICD shocks
CRT 6 months prior
• Meds: carvedilol, digoxin, torsemide, aldactone, coumadin
– No ACEI/ARB because of worsening renal function
• BP 100/80, HR 85, R 22, JVD to jaw, clear lungs, S3, TR, MR,
loud P2, palp liver edge, distended abd, no edema
• Hct 30%, Na 130, BUN 55, Cr 2.5, EKG afib, QRS 130 msec
CRT Nonresponders
So What?
For CRT nonresponders,
Consider
1)
2)
3)
4)
5)
It’s common (25-33%)
Definition of NR
Lead review or revision
Reprogramming
Advanced HF referral
Cha, Yong-Mei, et al. J Cardiovasc Electrophysiol 2007;18:1015-1019
• 53 year old man admitted with weight gain and dyspnea
despite increasing loop diuretics
–
–
–
–
Third admission this year
Idiopathic CMP (EF 25%)
PAF w/ inappropriate ICD shocks
CRT 6 months prior
• Meds: carvedilol, digoxin, torsemide, aldactone, coumadin
– No ACEI/ARB because of worsening renal function
• BP 100/80, HR 85, R 22, JVD to jaw, clear lungs, S3, TR, MR,
loud P2, palp liver edge, distended abd, no edema
• Hct 30%, Na 130, BUN 55, Cr 2.5, EKG afib, QRS 130 msec
ACE Inhibitor Intolerance:
Marker of Severe Disease
ACEI
No ACEI
• 259 consecutive HF
Age
55
60
admissions to BWH
If they can’t tolerate
RAS antagonists,
CAD
43%
65%
• 23% not on ACEI at d/c due
Duration
2
5
Be
very
worried
to circulatory-renal
NYHA 3-4
50%
82%
limitations:
Creatinine
1.2
2.5
– symptomatic  BP
– renal insufficiency
Death*
22%
57%
– hyperkalemia
*median follow-up, 8.5 months
Pinto et al., JACC 2003
• 53 year old man admitted with weight gain and dyspnea
despite increasing loop diuretics
–
–
–
–
Third admission this year
Idiopathic CMP (EF 25%)
PAF w/ inappropriate ICD shocks
CRT 6 months prior
• Meds: carvedilol, digoxin, torsemide, aldactone, coumadin
– No ACEI/ARB because of worsening renal function
• BP 100/80, HR 85, R 22, JVD to jaw, clear lungs, S3, TR, MR,
loud P2, palp liver edge, distended abd, no edema
• Hct 30%, Na 130, BUN 55, Cr 2.5, EKG afib, QRS 130 msec
If you hear a third heart sound in
the office…
SOLVD treatment Trial
• 2569 pts w/ CHF
• Enalapril vs placebo
• Baseline examinations
• Death or Hospitalization for CHF
• RR 1.30 (1.11-1.53, p<0.005)
• Adjusted for EF, NYHA, BP, HR,
Na, Cr, Age
Drazner MH, NEJM 2001;345:574
• 53 year old man admitted with weight gain and dyspnea
despite increasing loop diuretics
–
–
–
–
Third admission this year
Idiopathic CMP (EF 25%)
PAF w/ inappropriate ICD shocks
CRT 6 months prior
• Meds: carvedilol, digoxin, torsemide, aldactone, coumadin
– No ACEI/ARB because of worsening renal function
• BP 100/80, HR 85, R 22, JVD to jaw, clear lungs, S3, TR, MR,
loud P2, palp liver edge, distended abd, no edema
• Hct 30%, Na 130, BUN 55, Cr 2.5, EKG afib, QRS 130 msec
Escalating Creatinine
in Heart Failure Populations
2
1.9
1.8
1.7
1.6
1.5
1.4
1.3
1.2
1.1
1
SOLVD
CONSENSUS
RALES
COPERNICUS
ESCAPE
REMATCH
SOLVD: Impact of Renal Insufficiency
*
Total Mortality, %
50
40
*p<0.001
30
20
*
10
0
SOLVD Prevention
CrCl > 60
SOLVD Treatment
CrCl < 60
Dries et al., J Am Coll Cardiol 2001
Mortality Risk of
Decompensated
Heart Failure
1) BUN > 43 mg/dL
2) SBP <115 mmHg
1) BUN > 43 mg/dL
2) SBP <115 mmHg
3) SCr > 2.75 mg/dL
3) SCr > 2.75 mg/dL
Fonorow G, et al. JAMA 2005
Decompensated Heart Failure
CART analysis
Azotemia confers a high mortality
Fonorow G, et al. JAMA 2005
Prognostic Significance of Worsening
Renal Function During HF Admission
*Worsening Renal Function = Cre   0.3
No WRF
(n=731)
WRF
(n=273)
LOS > 10 days
9%
28%
Complication
20%
38%
Mortality
1%
7%
Gottlieb et al., J Card Failure 2002:8;136
When the Creatinine Rises…
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•
•
•
•
•
•
•
•
Patient can’t go home
Diuretic doses are often decreased
ACE inhibitors/ARBs are often discontinued
Other medications are renally dosed
Inotropes may be initiated
PA catheter may be placed
Foley catheter may be re-placed
Cardiac US may be ordered
Renal US may be ordered (and is rarely helpful)
Worsening Renal Function and CHF
Who’s at risk?
Hazard
Ratio
Weight
H/o CHF
1.3
1
DM
1.4
SBP>160
% WRF
RR
0
9.8
1.0
1
1
18.7
1.9
1.4
1
2
20.3
2.1
1.5 ≤ Cr ≤ 2.5
2.1
2
3
30.3
3.1
Cr ≥ 2.5
3.5
3
4+
52.8
5.4
Risk Factor
Forman, JACC 04
Score
P<0.001
Diuretics Decrease GFR in HF
15
10
GFR (% change)
N = 16
NYHA III
LVEF = 28%
Placebo
5
0
-5
80 mg IV Furosemide
-10
-15
-20
-25
0
500
1000
1500
2000
2500
Cumulative Urine Output, 0–8 h (mL)
Gottlieb et al., Circulation 2002;105:1348
Hemodynamic Response to IV Furosemide
in Heart Failure
Hemodynamic
Baseline
20 min after
Lasix 40 mg IV
P
PAWP (mm Hg)
28 ± 7
33 ± 9
<0.01
SVI (mL/min/m2)
27 ± 8
24 ± 7
<0.01
HR (bpm)
87 ± 13
91 ± 16
<0.01
MAP (mm Hg)
90 ± 15
96 ± 15
<0.01
SVR (dyne • s/cm5)
1454 ± 394
1676 ± 415
<0.01
PRA (ng/mL)
9.9 ± 8.5
17.8 ± 16
<0.05
PNE (pg/mL)
667 ± 390
839 ± 368
<0.01
Francis et al., Ann Int Med 1985;103:1
Diuretics and arrhythmic death?
Cooper HA, et al. Circulation 1999;100:1311-1315
Diuretic Resistance
“a clinical state in which diuretic response is diminished or lost
before the therapeutic goal of relief from edema has been reached”
“Braking Phenomenon”
A decrease in response to a diuretic
after the first dose
Mechanisms
1)
2)
3)
4)
5)
Poor oral bioavailability
Tubular hypertrophy to compensate for salt loss
Renal insufficiency
Neurohormonal mechanisms
Reduced renal blood flow
Brater DC. N Engl J Med. 1998;339:387
When the Diuretics Don’t Work….
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•
•
•
•
Restrict daily fluid intake (1.0-1.5 L)
Aggressive restriction of daily salt intake (≤2 g)
Stop NSAIDs
Decrease beta blockade
Give PO short-acting loop diuretic in several divided
(and increasing) doses, bolus, or continuous IV administration
• ?Nesiritide
• Use sequential nephron blockade by adding to loop diuretic
– thiazide diuretic
– Aldosterone antagonist
– short-term acetazolamide
More than 50% of Patients Have Little or no
Weight Loss During Hospitalization
33%
35
Patients (%)
30
24%
25
20
13%
15
10
7%
15%
6%
5
3%
2%
(5 to 10)
(>10)
0
(<-20)
(-20 to -15) (-15 to -10) (-10 to -5)
(-5 to 0)
(0 to 5)
Change in Weight (lbs)
Fonarow GC. Rev Cardiovasc Med. 2003; 4 (Suppl. 7): 21
Inotropic Therapy: Variable Effects
Colucci et al., Circulation 1986;73:III175
Mortality in Large Placebo-Controlled Trials
of Inotropes for Heart Failure
Trial
Inotrope
NYHA
N
Mortality vs Placebo
VEST
Vesnarinone
III, IV
3833
11% Increase
Xamoterol
Xamoterol
III, IV
516
Hazard ratio: 2.5
PRIME II
Ibopamine
III, IV
1906
Hazard ratio: 1.26
PICO
Pimodendan
II, III
317
Hazard ratio: 1.8
Inotropes should not be used for the
PROMISE
Milrinone
III, IV 1088 28% Increase
routine management of the cardiorenal syndrome
PROMISE = Prospective Randomized Milrinone Survival Evaluation; VEST = Vesnarinone Trial;
PRIME = Prospective Randomized Ibopamine Mortality Evaluation; PICO = Pimobendan in
Congestive Heart Failure
Felker GM, O’Connor CM. Am Heart J. 2001;142:393–401.
Hemodynamics and
Aggravated Renal Dysfunction
No ARD
+ ARD
RAP
12
9
12
10
Cardiac index
2.1
2.4
2.3
2.3
SVR
1470 1100
1400 1200
Renal Perf Press
67
66
61
64
No obvious hemodynamic difference…..
Weinfeld, Chertow, Stevenson Am Heart J 1999
Neurohormonal Regulation of
Renal Function in CHF
SNS
RAAS
Endothelin
Arginine Vasopressin
Adenosine
Natriuretic Peptides
Prostaglandins
Nitric Oxide
Bradykinin
Vasocontrictors
Na/H20 Retentive
Vasodilators
Na/H20 Excretory
Decompensated HF
No Standard of Care
• Wide variability in clinical practice
• Few randomized controlled trials
• Guidelines focus on:
– stable outpatients
– systolic (“low EF”) HF
• Intravenous versus oral agents
• Unclear endpoints to hospitalization
• What is appropriate post-discharge care?
What are the options?
•
•
•
•
•
•
Hemodynamic guided management
Vasopression antagonists (“Vaptans”)
Adenosine antagonists
Natriuretic peptides
Ultrafiltration
Advanced HF referral
Ultrafiltration for Fluid Retention
in Heart Failure
•
•
•
•
•
•
Acute reductions in filling pressures
CO - no change or increased
Serum norepinephrine levels decreased
Improved lung compliance
Improved exercise capacity
Mixed effects on renal function
Guazzi et al 1987,1990
Fauchald et al, 1986
Simpson et al,1985
Agostini et al,1993
Inoue et al, 1992
UF in refractory CHF
• 24 pts with Class IV HF
– >5 kg weight gain
– oliguria
• Single UF session in CCU
– mean time 9 hours
– mean volume removed
4,880 ml
• Results
– No hypotension
– Increased CO
– Decrease SVR
Marenzi JACC 2001
Ultrafiltration in Diuretic Resistance
Decreasing Length of Stay
EUPHORIA Trial
19 pts w/ CHF and diuretic
resistant
• Furosemide > 80 mg
• SCr > 1.5 mg/dl
• Before IV diuretics
Avg 8367  4232 cc removed
2.6 treatments
No readm w/in 30d
CHF Solutions
•
•
•
•
•
•
•
•
•
Ultrafiltration, not dialysis
Two Peripheral IVs (CL preferred)
100-500 ml/hr fluid removal over 24 hrs
Extracorporeal blood volume ~ 40 ml
Little hemodynamic effect
Systemic anticoagulation suggested
Limited need for nursing support
Minimal electrolyte shifts (isotonic filtrate)
Greater total body Na removal than
diuretics for given volume
The UNLOAD Trial

Efficacy
• Weight loss at 48 hours after randomization
• Dyspnea score at 48 hours after randomization

Safety
• Changes in serum blood urea nitrogen,
creatinine, and electrolytes at 8, 24, 48 and 72
hours after randomization, discharge, 10, 30 and
90 days
• Episodes of hypotension during the first 48
hours after randomization
The UNLOAD Trial
• Ultrafiltration arm
• Ultrafiltration rate ≤ 500 cc/hour
• Duration/rate of fluid removal decided by treating
physicians
• IV diuretics prohibited during ultrafiltration
• Standard Care arm
• IV diuretics as bolus or continuous infusions
• IV doses ≥ 2 times daily PO dose for the first 48
hours after randomization
Primary
PrimaryEnd
End Point
Point
Weight
Weight Loss
Loss at
at 48
48 Hr
Hr
Freedom From
Re-hospitalization for Heart
Failure
UF decreased:
1) % pts requiring re-hospitalization
2) Number of HF re-hospitalizations
3) Days of re-hospitalization for HF
4) ED and unscheduled office visits
Safety End Points: Change in
Serum Creatinine
• 53 year old man admitted with weight gain and dyspnea
despite increasing loop diuretics
–
–
–
–
Third admission this year
Idiopathic CMP (EF 25%)
PAF w/ inappropriate ICD shocks
CRT 6 months prior
• Meds: carvedilol, digoxin, torsemide, aldactone, coumadin
– No ACEI/ARB because of worsening renal function
• BP 100/80, HR 85, R 22, JVD to jaw, clear lungs, S3, TR, MR,
loud P2, palp liver edge, distended abd, no edema
• Hct 30%, Na 130, BUN 55, Cr 2.5, EKG afib, QRS 130 msec
When to get worried…
•
•
•
•
•
Recurrent hospitalizations
CRT nonresponders
Persistence
of thirdget
heart
sound with
on exam
(It won’t
better
time)
Inability to tolerate RAS antagonists and/or beta blockers
Renal insufficiency is present
•
•
•
•
•
Poor or worsening functional capacity
RV dysfunction is present
High BNP levels
Recurrent ventricular arrhythmias
“Diastolic HF” in absence of hypertension
Medically Refractory
Heart Failure?
• Persistent symptoms despite:
–
–
–
–
RAS antagonism with ACEI/ARB/Aldo antagonists
Beta blockers titrated to target doses
Device therapy (ie. ICD/CRT)
Addressing comorbidities (e.g. sleep apnea, anemia,
etc.)
– Participation in HF Disease Management Program
• Inability to establish euvolemia without
aggravating renal function
• Inability to keep out of the hospital