1 2.) Pro-BNP Secreted 1.) Stretching / 3.) Pro-BNP Cleaved - - PDF document

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Matthew Strehlow, MD, Clinical Associate Professor EM/Surgery Director, Clinical Decision Unit Stanford University Management Hyper-/normotensive

– NIPPV – Vasodilators – Diuretics

Management Hypotensive

– IV fluids – Inotropes – Vasopressors

Diagnosis

• Clinical predictors
• BNP & NT pro-BNP
• Ultrasound

Disposition

• 80 F with hx of CHF and COPD

complaining of severe SOB

– T 36 HR 90 BP 140/65 RR 30 SaO2 90% – B rales and wheezes – +JVD – BLE edema

• ECG: normal
• CXR: cardiomegaly

Decreased Risk:

• No history of heart failure

– LR = 0.45

• No dyspnea on exertion

– LR = 0.48

• No rales

– LR = 0.51

• No cardiomegaly on CXR

– LR = 0.51

• Normal ECG

– LR = 0.64

Increased Risk:

• History of heart failure

– LR = 5.8

• PND

– LR = 2.6

• S3

– LR = 11

• Congestion on CXR

– LR = 12

• Atrial fibrillation

– LR = 3.8

Wang CS et al. JAMA 2005

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3.) Pro-BNP Cleaved

NH2 NH2 COOH

BNP NT pro-BNP

NH2 COOH COOH

1.) Stretching / Stress

Europa-trail.org

COOH NH2 NH2 NH2

2.) Pro-BNP Secreted

COOH COOH

Specificity (False-Positive)

Moe et al. Circulation 2007

0.0 0.2 0.4 0.6 0.8 1.0 0.0 0.2 0.4 0.6 0.8 1.0

Sensitivity (True-Positive)

Clinical Judgement NT-proBNP Clinical Judgement + NT-proBNP Pre-test Probability Post-test Probability for BNP<105 pg/ml Post-test Probability for BNP>300 pg/ml

Korenstein et al. BMC 2007

10% 2% 46% 30% 5% 77% 50% 12% 88% 70% 25% 95% 90% 56% 99%

Age All <50 50-70 >70 Rule Out

<100+ <300* <300* <1200‡

Sens/Spec

90%/74% 99%/85% 99%/85% 97%/55%

Rule In

>400+ >450* >900* >4500‡

Sens/Spec

81%/90% 93%/95% 91%/80% 64%/86%

+Korenstein BMC Emerg Med 2007 *Januzzi, Jr. et al Am J Cardiol 2005 ‡Berdague et al. Am Heart J 2006

• Renal failure

– BNP as “rule out” (<100 or <200) if GFR <60

• Severe sepsis

– High elevations in both (BNP & NT pro-BNP)

• Pulmonary embolus

– Moderate elevations in large PEs

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• Greatest utility if diagnosis unclear
• Multiple conditions cause “false” elevations

– (especially sepsis and renal failure)

• Know individual test characteristics!
• 80 F with hx of CHF and COPD

complaining of severe SOB

– T 36 HR 90 BP 140/65 RR 30 SaO2 90% – B rales and wheezes – +JVD – BLE edema

• ECG: normal
• CXR: cardiomegaly
• BNP: Pending
• Elevated right heart filling pressures

– Examine IVC or IJ to estimate RAP

• Extravascular lung water

– Examine lungs looking for “B lines” B lines

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Courtesy of Anderson et al. Am J EM 2013

• 2 Lung Zones*

– Both positive - LR 4.73 – Both negative - LR 0.3

• Alternative^

– Sum B lines in all 8 zones, if >10 then LR 2.8

^Anderson et al. Am J EM 2013 *Litelpo et al. Acad Emerg Med 2009

• Elevated right heart filling pressures

– Examine IVC or IJ to estimate RAP

• Extravascular lung water

– Examine lungs looking for “B lines” Distance

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• Elevated RAP (>10mmHg)*

– IVC >2cm - LR 4.7

*Blair JE, et al. Am J Cardiology 2009

• Alternatives^#

– Collapsibility index <20% – Jugular venous pressure >8 cm

^Anderson et al. Am J EM 2013

#Cheng et al. J Emerg Med 2012

• Elevated right heart filling pressures

– Examine IVC or IJ to estimate RAP

• Extravascular lung water

– Examine lungs looking for “B lines”

• Combined lung edema and elevated RAP

– Both positive - LR 13 (for acute heart failure)

High risk findings

– Hx of CHF – PND – S3 – Congestion (CXR) – A-fib

Low risk findings

– No hx of CHF – No DOE – No rales – No cardiomegaly – Normal ECG

• BNP – consider if unsure of diagnosis
• Ultrasound – B lines and elevated RAP

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• 80 F with hx of CHF and COPD

complaining of severe SOB

• ECG: normal
• CXR: cardiomegaly
• BNP: 450
• US: + B lines &

elevated RAP

• 57 yo male with a history
• f CHF c/o severe SOB.
• PE:

– HR 120, BP 185/110, RR 30, SaO2 85% RA – Diaphoretic – Bilateral rales – BLE edema Which of the following methods of O2

delivery decreases mortality?

• A. Non-rebreather face mask
• B. Bi-level positive airway pressure

(BiPAP)

• C. Continuous positive airway pressure

(CPAP)

• D. All of the above are equivalent

Which of the following methods of O2

delivery decreases mortality?

• A. Non-rebreather face mask
• B. Bi-level positive airway pressure

(BiPAP)

• C. Continuous positive airway pressure

(CPAP)

• D. All of the above are equivalent

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Noninvasive Ventilation in Acute Cardiogenic Pulmonary Edema

ESTABLISHED IN 1812 JULY 10, 2008 VOL 359 NO. 2

• 1069 ED patients randomized to 2 hrs of:
• BiPAP
• CPAP
• Oxygen by NC or FM

62/367 (17%) Patients Crossed Over!!!

• Improves symptoms of dyspnea
• Consider in patients with:

– Significant respiratory symptoms – O2 saturation <90%

• Unclear effect on mortality and ETI

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How much IV furosemide should be given to this patient as part of his initial stabilization? His outpatient regimen is 80 mg/day.

• A. None
• B. 40 mg
• C. 80 mg
• D. 160 mg

How much IV furosemide should be given to this patient as part of his initial stabilization? His outpatient regimen is 80 mg/day.

• A. None
• B. 40 mg
• C. 80 mg
• D. 160 mg
• 1. Low cardiac output and over-diuresis

leads to WRF

• 2. WRF during hospitalization for AHF leads

to increased mortality

• Double-blind RCT with 308 patients
• Administered loop diuretics for 72 hrs by
• Bolus or Infusion
• High or Low doses
• Outcomes: symptoms & rising creatinine

Diuretic Strategies in Patients with Acute Decompensated Heart Failure

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• No difference between groups

(bolus vs infusion or high vs low dose)

• Symptoms
• Creatinine
• Adverse outcome (death, ED visits, and

rehospitalization)

Diuretic Strategies in Patients with Acute Decompensated Heart Failure

• 1. Low cardiac output and over-diuresis

leads to WRF

• 2. WRF during hospitalization for AHF leads

to increased mortality

• 1. Low cardiac output and over-diuresis

leads to WRF

• 2. WRF during hospitalization for AHF leads

to increased mortality

• 1. Elevated CVP and venous congestion

lead to worsening renal failure

• 2. Transient WRF may not lead to increased

mortality How much IV furosemide should be given to this patient as part of his initial stabilization? His outpatient regimen is 80 mg/day.

• A. None
• B. 40 mg
• C. 80 mg
• D. 160 mg

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• Delayed onset

– 45 to 120 minutes

• Diuretic

resistance

– Daily users

LOOP DIURECTICS - Minutes to Onset of Action

30 60 90 120

Healthy CHF

Mattu et al. Emerg Med Clin North Am 2005

• Venous dilation

– Healthy subjects – Maximized at 20 mg IV

• Arterial constriction

– CHF patients – Predominates early FUROSEMIDE EFFECT ON CARDIAC PHYSIOLOGY

PVR SVR MAP HR RAFP SV

• 25-50% of

patients in AHF are intravascularly volume low

• Improves symptoms of dyspnea
• Caution using as a single agent during

initial stabilization

• Effect on outcomes is unknown
• Adverse cardiovascular effects early

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“Intravenous Nitrates in the Prehospital Management of Acute Pulmonary Edema”

• Bertini, et al., Ann Emerg Med. 1997

“Intravenous Nitroglycerin Boluses in Treating Patients with Cardiogenic Pulmonary Edema”

• Nashed, et al., Am J Emerg Med.

“Emergency Treatmet of Severe Cardiogenic Pulmonary Edema with Intravenous Isosorbide-5- Mononitrate”

• Harf, et al., Am J Cardiol. 1988

“Comparison of Nitroglycerin, Morphine and Furosemide in Treatment of Presumed Pre-hospital Pulmonary Edema”

• Hoffman, et al., Chest. 1987

Nitrate Properties  Venous and arterial dilation  Recommended in cardiac ischemia  Rapid onset of action  Short half-life  Minimal side effects

What is optimal method of nitrate administration in this patient?

• A. Nitropaste

1” to chest wall

• B. Nitro SL

0.4mg Q 5 min x 3

• C. Nitro infusion

20 mcg/min titrated 10mcg/min Q 5 min

• D. Nitro infusion

100 mcg/min titrated 20mcg/min Q 3 min

What is optimal method of nitrate administration in this patient?

• A. Nitropaste

1” to chest wall

• B. Nitro SL

0.4mg Q 5 min x 3

• C. Nitro infusion

20 mcg/min titrated 10mcg/min Q 5 min

• D. Nitro infusion

100 mcg/min titrated 20mcg/min Q 3 min

*Death, Mechanical Ventilation, Myocardial Infarction p<0.05

Cotter et al. Lancet 1998

• 3 mg isosorbide

dinitrate IV Q 5 min (600 mcg/min)

• No hypotension

requiring treatment

• No SBP <85mmHg

ADVERSE EFFECTS* - Isosorbide Dinitrate vs. Furosemide

13 24 10 20 30 40 50

Isosorbide DiNitrate Furosemide

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• Nitropaste

– Erratic absorption – Slow onset of action

• Nitropaste

– Erratic absorption – Slow onset of action

• Nitroglycerin SL

– Equivalent to 60 to 80 mcg/min

• Nitropaste

– Erratic absorption – Slow onset of action

• Nitroglycerin SL

– Equivalent to 60 to 80 mcg/min

• Nitroglycerin Infusion

– Start ≥100 mcg/min and rapidly titrate to:

• symptom improvement
• 30% reduction in MAP
• MAP <90
• First line therapy
• Use in patients with hyper-/normotensive
• High doses are safe and effective

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Which is the most appropriate therapy in

addition to oxygen for this patient’s acute heart failure?

• A. Morphine 4mg IV
• B. Serelaxin 30 mcg/kg/day infusion
• C. Nesiritide 2 mcg bolus and 0.01

mcg/kg/min infusion

• D. Captopril 25 mg SL

Which is the most appropriate therapy in

addition to oxygen for this patient’s acute heart failure?

• A. Morphine 4mg IV
• B. Serelaxin 30 mcg/kg/day infusion
• C. Nesiritide 2 mcg bolus and 0.01

mcg/kg/min infusion

• D. Captopril 25 mg SL
• Indirect venodilator
• Little outcomes data but…

– Increased rate of intubations – Increased rate of ICU admissions

Hoffman et al. Chest 1987 Sacchetti et al. Am J Emerg Med 1999

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• Double-blind RCT with 1161 patients
• Administered serelaxin infusion for 48 hrs in

addition to standard therapy

• 30 mcg/kg/day
• Initiated within 16 hours of presentation
• Primary outcomes: Improvement of symptoms

Teerlink et al. Lancet 2013

• No difference in Likert scale of symptoms
• All cause mortality was decreased at 6 months
• placebo, 65 deaths; serelaxin, 42; HR 0.63,

95% CI 0.42–0.93; p=0.019

p=0.04 Sackner-Bernstein et al. Circulation 2005 p=0.003 Sackner-Bernstein et al. JAMA 2005

MORTALITY Nesiritide vs. Control

4.0% 7.2% 0.0% 1.0% 2.0% 3.0% 4.0% 5.0% 6.0% 7.0% 8.0%

Nesiritide Control WORSENING RENAL FUNCTION Nesiritide vs. Control

21% 15% 0% 5% 10% 15% 20% 25%

Nesiritide Control

Effect of Nesiritide in Patients with Acute Decompensated Heart Failure

ESTABLISHED IN 1812 JULY 7, 2011 VOL 365 NO. 1

• Double-blind RCT of Nesiritide vs placebo
• 7141 patients
• Addition to standard therapy
• Results: No difference in outcomes trend

towards symptom improvement

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• Decrease

– Preload – Afterload – MAP

• Increase

– Cardiac output – Stroke volume

• No effect

– Heart rate

P=0.002 Sacchetti et al. Am J Emerg Med 1999

Risk of Admission and ETI with ACEI

• Nesiritide - 2nd line
• ACE Inihibitor - 3rd line or as an adjunct
• Serelaxin - Safety profile established,

small symptom benefit

• Morphine - not recommended
• CPAP & BiPAP
• Improves symptoms
• Loop Diuretics
• Bolus dosing appropriate
• Caution during initial stabilization
• Nitrates
• High doses are safe and effective
• 60 yo F with severe

CHF and SOB

• Physical exam

– HR 100 – SBP 95/50 – RR 25 – SaO2 98% FM

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Gheorghiade M, et al. JAMA 2006

Which of the following medications would you administer in this patient’s initial management?

• A. Nitroglycerin 20-50 mcg/kg/min IV
• B. NS 250 mL IV bolus
• C. Dobutamine 5-25 mcg/kg/min
• D. Dopamine 5-25 mcg/kg/min
• BP (100-110 mmHg), other

perfusion signs normal

• BP (80-100 mmHg), other

perfusion signs abnormal

• BP (<80 mmHg), other

perfusion signs abnormal

• Nitrates – moderate dose
• Diuretics – consider low dose
• IV fluid – trial small bolus
• Inotrope – consider if BP<90
• IV fluid – trial small bolus
• Vasopressor – severe shock
• Clinical effect

– Increases cardiac output – May increase dysrhythmias and myocardial necrosis – No beneficial effect on mortality

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• No difference in overall mortality
• Cardiogenic shock patients receiving

Dopamine had a higher mortality (p=0.03) and more dysrhythmias

• BP (100-110 mmHg), other perfusion signs

normal

– Nitrates and diuretics

• BP (80-100 mmHg), other perfusion signs

abnormal

– IV fluids and dobutamine

• BP (<80 mmHg), other perfusion signs

abnormal

– IV fluids and norepinephrine

• 1 million ED visits for AHF annually

– 80% admitted (800,000 admits/year)

• Cost estimated US 40 billion dollars

annually

• Highest readmission rate of any ED

diagnosis (≈25% at 30 days)

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• Prevention Quality Indicator #8

– Rate of heart failure admissions

• 1. Prevent the initial admission
• 2. Prevent re-admission
• 80 yo F with CHF and acute heart failure

– T 36 HR 90 BP 140/65 RR 30 SaO2 90

• ECG: normal
• CXR: cardiomegaly
• BNP 450
• K+ 3.4
• Cr 1.7
• TnI 0.01
• What is this patient’s 7-day mortality

rate?

• A. 2%
• B. 5%
• C. 8%
• D. 12%
• What is this patient’s 7-day mortality

rate?

• A. 2%
• B. 5%
• C. 8%
• D. 12%

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EHMRG 7-Day Risk Score Risk score 41 7-day mortality 1.8%

Lee et al. Annals Intern Med 2012

• Pre-existing heart failure
• Stable hemodynamic and respiratory status

– SBP >120 mmHg, RR <32, no NIPPV currently

• Labs and ECG

– BUN <40 mg/dL – Creatinine <3 mg/dL – Troponin not elevated – BNP <1000 pg/mL or NT-BNP <5000 pg/mL – ECG unremarkable

• Initial response to therapy (sxs, urine output)
• Adequate availability of follow-up

Peacock et al. Acute Cardiac care 2009

• Observe response to therapy
• Identify high-risk features

– Serial Troponin, ECG, electrolytes and renal function

• Diagnostic testing

– Echocardiography is not previously performed

• Heart failure education

– Heart failure education team (e.g. nurse)

• Guideline directed medical therapy

– Evaluate for appropriate outpatient management

• Arrange early follow-up
• Optimize medication regimen

Collins et al. J Am Colleg Cardiol 2013

High risk findings

– Hx of CHF – PND – S3 – Congestion (CXR) – A-fib

Low risk findings

– No hx of CHF – No DOE – No rales – No cardiomegaly – Normal ECG

• BNP – consider if unsure of diagnosis
• Ultrasound – B lines & elevated RAP

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Hyper-/normotensive

• Nitrates

– High doses are safe and effective

• Diuretics

– Consider after vasodilation

Hypotensive

• Assess perfusion and degree of shock
• Treat with

– Nitrates and diuretics – IV fluids, inotropes, vasopressors