2/29/2016 1 Management of Acute Heart Failure and Cardiogenic Shock www.fshp.org Brittany D. Bissell, Pharm.D. PGY-2 Critical Care Pharmacy Resident Jackson Memorial Hospital | Miami, Florida DISCLOSURE STATEMENT I have no actual or potential conflicts of interest in relation to this presentation. 2 TECHNICIAN OBJECTIVES • Explain management principles for left ventricular failure • Describe treatment options for end-stage heart failure • List pharmacologic therapies for cardiogenic shock 3 PHARMACIST OBJECTIVES • Assess the hemodynamic dysregulation implicated in the pathophysiology of heart failure • Develop recommendations for preload optimization • Investigate evidence for current options for the management of cardiogenic shock 4
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2/29/2016
1
Management of Acute Heart Failure and Cardiogenic Shock
www.fshp.org
Brittany D. Bissell, Pharm.D.PGY-2 Critical Care Pharmacy Resident
Jackson Memorial Hospital | Miami, Florida
DISCLOSURE STATEMENT
I have no actual or potential conflicts of interest in relation to this presentation.
2
TECHNICIAN OBJECTIVES
• Explain management principles for left ventricular failure
• Describe treatment options for end-stage heart failure
• List pharmacologic therapies for cardiogenic shock
3
PHARMACIST OBJECTIVES
• Assess the hemodynamic dysregulation implicated in the pathophysiology of heart failure
• Develop recommendations for preload optimization
• Investigate evidence for current options for the management of cardiogenic shock
Positive inotrope activity independent of β stimulation
Reduction of pulmonary artery pressure
Significantly higher rates of hypotension compared to placebo
Dose range: 0.25 - 0.75 mcg/kg/min
Tariq, et al. Int J Mol Sci. 2015;16(12):29060-8.
35
MILRINONE
Felker, et al. . J Am Coll Cardiol. 2003;41(6):997-1003
949 patients receiving milrinone or placebo for
48-72 hours
36
MILRINONE
Abraham, et al. J Am Coll Cardiol. 2005;46(1):57-64.
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MECHANICAL
CIRCULATORY SUPPORT
38
MECHANICAL CIRCULATORY SUPPORT
INTRA-AORTIC
BALLOON PUMP
(IABP)
VENTRICULAR
ASSIST DEVICE
(VAD)
EXTRACORPOREAL
MEMBRANE
OXYGENATION
(ECMO)
Inflation facilitates coronary perfusion with increased diastolic pressure
Deflation augments left ventricular (LV) ejection through negative pressure
MECHANICAL CIRCULATORY SUPPORT
Long-term support of cardiac output
Blood removed from left ventricle and returned to ascending aorta
Pulmonary artery return for right ventricular support
Extracorporeal controller and power supply
Blood removed from femoral vein or inferior vena cava
Blood returned to right heart or femoral artery
Separate modes for goal outcomes
Subramaniam, et al. Best Pract Res Clin Anaesthesiol. 2015;29(2):203-27.Pratt, et al. Crit Care Med. 2014; 42:158–168Russell, et al. Circulation. 2009;120(23):2352-7.
IABP INDICATIONS FOR USE
40
Acute Coronary Syndromes•Cardiogenic shock in STEMI
•High-risk PCI or CABG
•STEMI and NSTEMI complications
•Refractory angina
Ventricular Arrhythmias
Refractory Heart Failure
Ihdayhid, et al. Curr Opin Cardiol. 2014, 29:285–292
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ANTICOAGULATION WITH IABP
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•Randomized controlled trial
•Heparin vs. placebo
•Ischemia 0.2 vs. 2.4%
•Bleeding 14.2 vs. 2.4%
2003
•Prospective cohort
•Heparin vs. selective
•Ischemia 0.5 vs. 0%
•Bleeding 38.5 vs. 25.4%
2008 •Retrospective study
•No anticoagulation
•Ischemia 3.4%
•Bleeding 4.2%
2012
Anticoagulation warranted for primary indications
Jiang, et al. J Zhejiang Univ Sci. 2003;4:607–11Cooper, et al. Acute Cardiac Care. 2008;10:214–20Kogan, et al. J Card Surg. 2012;27:434-437
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7 - Advanced NYHA III
6 - Exertion limited
5 - Exertion intolerant
4 - Resting symptoms
3 - Inotrope dependent
2 - Progressive decline
1 - Critical cardiogenic shock
Definitive Therapy Required
Months
Hours
Days
Feldman, et al. JHLT. 2013;32:157–187
INTERMACS HEART FAILURE PROFILES
43
MECHANICAL SUPPORT
Kirklin, et al. JHLT. 2014 ; 33(10): 996-1008
44
CRITERIA FOR IMPLANTATION
Peak oxygen consumption <14
mL/kg/minor
Inability to perform exercise
test
NYHA functional class IV
Left ventricular ejection fraction
<25%
Failed optimal management for
45/60 days or
7 days IABP-dependent or
14 days inotrope-dependent
Kirklin, et al. J Heart Lung Transplant. 2014;33:555–564
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MECHANICAL SUPPORT
Destination
Therapy (DT)
HEARTMATE II• Axial flow• Mechanical bearings• Larger in size• FDA approved for BTT: 75-90%
survival• FDA approved for DT: 58-61% survival• Increased hemolysis and thrombosis
HEARTWARE
• Centrifugal flow• Hydrodynamic bearings• Less experience with use• FDA approved for BTT: 90.7% survival• DT trial completed• Increased stroke and bleeding
Mancini, et al. Am Coll Cardiol. 2015;65:2542–55Lalonde, et al. J Card Surg. 2013;28:604–610
46
ANTIPLATELET THERAPY
HEARTWARE ADVANCE TRIAL
• Aspirin (ASA)• Warfarin to INR 2-3• INR<2 or ASA ≤81 mg
associated with increased thrombotic events
• Pump exchange rates decreased 55% with increase to aspirin 325 mg
including hypotension and arrhythmias despite symptom improvement
Tariq, et al. Int J Mol Sci. 2015;16(12):29060-8.
ULARITIDE
55
Synthetic form of urodilatin
with resistance to degradation
Diuresis
Natriuresis
Vasodilation
Hsiao, et al. Prog Cardiovasc Dis. 2016. [Epub ahead of print]
ULARITIDE
56
SIRIUS I
• 15- and 30-ng/kg/min
• Improvement in dyspnea
• Decreased mortality
SIRIUS II
• 15- and 30-ng/kg/min
• Improved dyspnea
• Improvement pulmonary pressures
• Decreased hospitalization
• Decreased mortality
TRUE-AHF
Hsiao, et al. Prog Cardiovasc Dis. 2016. [Epub ahead of print]
2/29/2016
15
TRUE-AHF
57
Co-Primary Outcome:
• Improved global assessment at 6, 24, and 48 hours without meeting criteria for worsening, including:
• Death within 48 hours
• Worsening of disease warranting intervention
• Worsening global assessment
Co-Primary Outcome:
• Freedom from cardiovascular mortality
Secondary Outcomes:
• N-terminal pro-BNP changes
• All-cause mortality and rehospitalization
• Cardiovascular rehospitaliation
Anker, et al. Eur Heart J. 2015;36(12):715-2
SERELAXIN
58
Human recombinant form
of relaxin
Upregulator of endothelin B receptors and nitric oxide production
Inhibition of angiotensin II
and endothelin potentiates
systemic and renal vasodilation
Anti-inflammatory
and anti-fibrotic properties
Hsiao, et al. Prog Cardiovasc Dis. 2016. [Epub ahead of print]
RELAX-AHF
59
Significantly reduced hospital stay, time to dyspnea improvement, and worsening of heart failure
Significant improvement in symptomatic visual analog scale
30 mcg/kg/day serelaxin versus placebo
Teerlink, et al, Lancet. 2013;381(9860):29-39.
RELAX-AHF
60
Felker, et al. J Am Coll Cardiol. 2014 ;64(15):1591-8.
2/29/2016
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Medication correlation with decompensation
Half-life longer than initial
critical period
Paradoxical activation of sympathetic
nervous system
61
BETA-BLOCKER CONSIDERATIONS
Jondeau , et al. JACC Heart Fail. 2015;3(8):654-6
62
BETA-BLOCKER THERAPY
IN-HOSPITAL MORTALITY
Prins, et al. JACC Heart Fail. 2015;3(8):647-53.
63
BETA-BLOCKER THERAPY
SHORT-TERM MORTALITY OR REHOSPITALIZATION
Prins, et al. JACC Heart Fail. 2015;3(8):647-53.
ASSESSMENT QUESTION
Increasing preload and/or inotropy are strategies for optimization of cardiac
output.
64
2/29/2016
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A primary principle in the management of left heart failure is
reduction of venous congestion.
65
ASSESSMENT QUESTION
The patient receives a HeartMate II ventricular assist device. The patient
should be bridged with heparin.
66
ASSESSMENT QUESTION
Management of Acute Heart Failure and Cardiogenic Shock
www.fshp.org
Brittany D. Bissell, Pharm.D.PGY-2 Critical Care Pharmacy Resident
Jackson Memorial Hospital | Miami, Florida
• Abraham WT, Adams KF, Fonarow GC, et al. In-hospital mortality in patients with acute decompensated heart failure requiringintravenous vasoactive medications: an analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). J Am CollCardiol. 2005;46(1):57-64.
• Anker SD, Ponikowski P, Mitrovic V, Peacock WF, Filippatos G. Ularitide for the treatment of acute decompensated heart failure: frompreclinical to clinical studies. Eur Heart J. 2015;36(12):715-2
• Brodie D, Bacchetta M. Extracorporeal membrane oxygenation for ARDS in adults. N Engl J Med. 2011;365(20):1905-14.• Cooper HA, Thompson E, Panza JA. The role of heparin anticoagulation during intra-aortic balloon counterpulsation in the coronary
care unit. Acute Cardiac Care 2008;10:214–20.• Cotter G, Felker GM, Adams KF, Milo-Cotter O, O'Connor CM. The pathophysiology of acute heart failure--is it all about fluid
accumulation? Am Heart J. 2008;155(1):9-18.• Cove ME, MacLaren G. Clinical review: mechanical circulatory support for cardiogenic shock complicating acute myocardial infarction.
Crit Care. 2010;14(5):235.• Di Somma S, Magrini L. Drug Therapy for Acute Heart Failure. Rev Esp Cardiol. 2015;68(8):706-13.• Esper SA, Levy JH, Waters JH, Welsby IJ. Extracorporeal membrane oxygenation in the adult: a review of anticoagulation monitoring
and transfusion. Anesth Analg. 2014;118(4):731-43• Feldman D, Pamboukian SV, Teuteberg JJ, et al. The 2013 International Society for Heart and Lung Transplantation Guidelines for
mechanical circulatory support: executive summary. J Heart Lung Transplant. 2013;32(2):157-87.• Felker GM, Benza RL, Chandler AB, et al. Heart failure etiology and response to milrinone in decompensated heart failure: results from
the OPTIME-CHF study. J Am Coll Cardiol. 2003;41(6):997-1003.• Felker GM, Teerlink JR, Butler J, et al. Effect of serelaxin on mode of death in acute heart failure: results from the RELAX-AHF study. J
Am Coll Cardiol. 2014 ;64(15):1591-8.• Gadepalli SK, Hirschl RB. Extracorporeal life support: updates and controversies. Semin Pediatr Surg. 2015;24(1):8-11.• Howlett JG. Acute heart failure: lessons learned so far. Can J Cardiol. 2011;27(3):284-95.• Hsiao R, Greenberg B. Contemporary Treatment of Acute Heart Failure. Prog Cardiovasc Dis. 2016 Jan 4. [Epub ahead of print]• Ihdayhid AR, Chopra S, Rankin J. Intra-aortic balloon pump: indications, efficacy, guidelines and future directions.Curr Opin Cardiol.
2014, 29:285–292• Jiang CY, Zhao LL, Wang JA, Mohammod B. Anticoagulation therapy in intra-aortic balloon counterpulsation: does IABP really need
anti-coagulation? J Zhejiang Univ Sci 2003;4:607–11.• Jondeau G, Milleron O. Beta-Blockers in Acute Heart Failure: Do They Cause Harm? JACC Heart Fail. 2015;3(8):654-6
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REFERENCES
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• Kirklin JK, Naftel DC, Pagani FD, et al. Sixth INTERMACS annual report: a 10,000-patient database. J Heart Lung Transplant.2014;33:555–564
• Kogan A, Preisman S, Sternik, et al. Heparin-free management of intra-aortic balloon pump after cardiac surgery. J Card Surg2012;27:434-437.
• Kreuziger LM. Management of anticoagulation and antiplatelet therapy in patients with left ventricular assist devices. J ThrombThrombolysis. 2015;39:337–344.
• Lalonde SD, Alba AC, Rigobon A, et al. Clinical Differences Between Continuous Flow Ventricular Assist Devices: A ComparisonBetween HeartMate II and HeartWare HVAD. 2013; J Card Surg, 28: 604–610
• Liu C, Liu K. Effects of glucocorticoids in potentiating diuresis in heart failure patients with diuretic resistance. J Card Fail.2014;20(9):625-9.
• Mancini D, Colombo PC. Left Ventricular Assist Devices: A Rapidly Evolving Alternative to Transplant. J Am Coll Cardiol.2015;65(23):2542-55
• Mebazaa A, Tolppanen H, Mueller C, et al. Acute heart failure and cardiogenic shock: a multidisciplinary practical guidance. IntensiveCare Med. 2016 Feb;42(2):147-63.
• Pratt AK, Shah NS, Boyce SW. Left ventricular assist device management in the ICU. Crit Care Med. 2014; 42:158–168• Prins KW, Neill JM, Tyler JO, Eckman PM, Duval S. Effects of Beta-Blocker Withdrawal in Acute Decompensated Heart Failure: A
Systematic Review and Meta-Analysis. JACC Heart Fail. 2015;3(8):647-53.• Russell SD, Rogers JG, Milano CA, et al. Renal and hepatic function improve in advanced heart failure patients during continuous-flow
support with the HeartMate II left ventricular assist device. Circulation. 2009;120(23):2352-7.• Slaughter MS, Naka Y, John R, et al. Post-operative heparin may not be required for transitioning patients with a HeartMate II left
ventricular assist system to long-term warfarin therapy. J Heart Lung Transplant. 2010;29, 616–624.• Subramaniam K. Mechanical circulatory support. Best Pract Res Clin Anaesthesiol. 2015;29(2):203-27.• Teerlink JR, Cotter G, Davison BA, et al. Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a
randomised, placebo-controlled trial. Lancet. 2013;381(9860):29-39.• Tariq S, Aronow WS. Use of Inotropic Agents in Treatment of Systolic Heart Failure. Int J Mol Sci. 2015;16(12):29060-8.• ter Maaten JM, Valente MA, Damman K, Hillege HL, Navis G, Voors AA. Diuretic response in acute heart failure-pathophysiology,
evaluation, and therapy. Nat Rev Cardiol. 2015;12(3):184-92.• Wiesen J, Ornstein M, Tonelli AR, Menon V, Ashton RW. State of the evidence: mechanical ventilation with PEEP in patients with