Transcript Nesiritide Use at the Texas Children’s Hospital

Treatment Strategies for ADHF Associated
AKI
John Lynn Jefferies, MD, MPH,
FAAP, FACC
Director, Cardiomyopathy, Advanced Heart Failure, and
Ventricular Assist Device Programs
Co-Director, Cardiovascular Genetics
Associate Professor, Pediatric Cardiology and
Adult Cardiovascular Diseases
The Heart Institute
Cincinnati Children’s Hospital
Jessup et al. Circulation 2009;119:1977-2016.
Pharmacologies in Heart Failure Management
ANP
BNP
NO
Bradykinin
Prostacyclin
Endothelin
Aldosterone
Angiotensin II
Vasopressin
Norepinephrine
Vasoconstriction
Vasodilation
Shah M et al. Rev Cardiovasc Med. 2001;2(suppl 2):S2
Hemodynamic Profile Assessment
Congestion at Rest
No
Yes
Signs/symptoms
of congestion
No
Warm & Dry
Warm & Wet
Yes
Cold & Dry
Cold & Wet
 Orthopnea/PND
 JVD
 Ascites
 Edema
 Rales (rare in HF)
Low
Perfusion
at Rest
Possible evidence of low perfusion
 Narrow pulse pressure
 Cool extremities
 Sleepy/obtunded  Hypotension with ACE inhibitor
 Low serum sodium  Renal dysfunction (one cause)
Stevenson LW. Eur J Heart Fail. 1999;1:251
Patient Selection and Treatment
Congestion at Rest
Low No
Perfusion
at Rest
No
Yes
Warm & Dry
PCWP normal
CI normal
Warm & Wet
PCWP elevated
CI normal
(compensated)
Cold & Dry
Cold & Wet
Yes PCWP low/normal PCWP elevated
CI decreased
CI decreased
Normal
SVR
Inotropic Drugs
Dobutamine
Milrinone
Calcium Sensitizers
Natriuretic
Peptide
Nesiritide
or
Vasodilators
Nitroprusside
Nitroglycerin
High
SVR
Stevenson LW. Eur J Heart Fail.
1999;1:251
Proven Outcomes for Heart Failure
Therapies
• Improve Survival
–
–
–
–
ACE inhibitor
ARB
Beta blocker
Aldosterone receptor
antagonist
– Hydralazine/longacting nitrates
• Reduce Hospitalization
–
–
–
–
ACE inhibitor
ARB
Beta blocker
Aldosterone receptor
antagonist
– Hydralazine/long-acting
nitrates
– Digoxin
Intravenous Agents for Heart Failure
CO
PCWP
BP
ArrhythHR
mia












+++
+++
+++
0
0
0
?
?

Dobutamine









+++
0

Milrinone





+
++

Nitroglycerin





+++
0

Nesiritide





++
++

Nitroprusside





++++
0

Therapy
Dopamine
(ng/kg/min)
Low (<3)
Mod (3–7)
High (7–15)
Shorter
Onset
Longer DiureOffset
sis
Young JB. Rev Cardiovasc Med .2001;2(suppl 2):S19
Ventricular Remodeling
Ventricular Remodeling After Acute Infarction
Global remodeling
(days to months)
Initial infarct
Expansion of infarct
(hours to days)
Ventricular Remodeling in Diastolic and Systolic HF
Normal heart
Dilated heart
(systolic HF)
Hypertrophied heart
(diastolic HF) Jessup M et al. N Engl J Med. 2003;348:2007
Pharmacologies in Heart Failure
Management
Cardiac
 Lusitropic
 Antifibrotic
 Antiremodeling
Hemodynamic
(balanced vasodilation)
 Veins
 Arteries
 Coronary arteries
Neurohormonal
  aldosterone
  endothelin
  norepinephrine
Renal
  sodium and water excretion
Abraham WT et al. J Card Fail. 1998;4:37
Clemens LE et al. J Pharmacol Exp Ther. 1998;287:67
Marcus LS et al. Circulation. 1996;94:3184
Tamura N et al. Proc Natl Acad Sci U S A. 2000;97:4239
Zellner C et al. Am J Physiol. 1999;276(3 pt 2):H1049
Sites of Action for HF Therapies
Beta blockers
Heart
Digoxin,
inotropes
Cardiacresynchronization
therapy
ACE inhibitors,
angiotensin receptor blockers,
aldosterone antagonists
Diuretics, aldosterone
antagonists,
nesiritide
Kidney
ACE inhibitors,
angiotensin receptor blockers,
vasodilators, alpha blockade,
Jessup M, Brozena S. N Engl J Med. 2003;348:2007
nesiritide, exercise
Peripheral
Arteries
Current Heart Failure Strategies
• “Primum non nacere” (First, do no harm)
• Factors predicting quality outcomes
– Correct diagnosis
– Appropriate management strategies
• Timing is everything
– Utilization of available resources
thoughtfully
– Learn from the adult literature…
Management of End-Stage Heart Failure
Jessup et al. Circulation 2009;119:1977-2016.
Management of End-Stage Heart Failure
Jessup et al. Circulation 2009;119:1977-2016.
Management of End-Stage Heart Failure
Jessup et al. Circulation 2009;119:1977-2016.
Patients with Reduced Left
Ventricular Function
Jessup et al. Circulation 2009;119:1977-2016.
Ventricular Assist Devices
The Next Frontier
Ultrafiltration
• Ultrafiltration (UF) is a potentially attractive
treatment strategy for patients with volume
overload with CRS
– UF has no effect on serum electrolytes
– Results are rapid
– Volume removed is easily controlled and
predictable
– Does not stimulate the neurohormonal system
– Restores responsiveness to diuretics in patients
with diuretic resistance
Costanzo et al. Semin Nephrol 2012;32:100-111.
Ultrafiltration
Costanzo et al. J Am Coll Cardiol 2007;49:675-683
Costanzo et al. J Am Coll Cardiol 2007;49:675-683.
Costanzo et al. Semin Nephrol 2012;32:100-111
Bart et al. J Card Fail 2012;18:176-182.
Vasopressin Antagonists
• Arginine vasopressin (AVP) levels are often
elevated in heart failure
• Leads to water retention, hyponatremia,
vasoconstriction, and myocardial fibrosis
• AVP antagonists (Conivaptan and Tolvaptan)
are available in the US
• Enhance free water clearance without
electrolyte loss
• No effect on renal function
Udelson et al. J Cardiac Fail 2011;17:973-981.
Udelson et al. J Cardiac Fail 2011;17:973-981.
Conclusions
• Current treatment of decompensated heart
failure involves multiple possible
therapeutic strategies
• Many of these are harmful to the kidney
and may worsen AKI
• Newer technologies may favorably impact
markers of AKI and result in less long-term
morbidity and mortality
Conclusions
• The treatment of acute decompensated heart
failure requires recognition that HF is a
syndrome involving complex interactions
• Preservation of kidney function is critical to
avoidance of readmission and survival
• Consultation with Cardiologists that have
recognized expertise in the management of HF
is strongly recommended