Right Heart Strain in Life- Threatening Pulmonary Embolism · 2018-01-22 · 1/22/2018 1 Right Heart Strain in Life-Threatening Pulmonary Embolism Mark Favot, MD, FACEP Assistant

1/22/2018

1

Right Heart Strain in Life-

Threatening Pulmonary

EmbolismMark Favot, MD, FACEP

Assistant Professor, Emergency MedicineWayne State University School of

MedicineJanuary 28th, 2018

Incomplete Information

1/22/2018

2



• CT #1:

• Multiple large acute

pulmonary emboli

• Upper, lower & middle

right pulmonary artery

branches

• CT #2:

• Small acute

pulmonary embolism

segmental branch

right upper lobe

1/22/2018

3

Case #1

• 43yo f

• Dyspnea x 1mo

• Preceded by URI sx

• 36o C, 140/64, 84, 18

• SpO2 99% RA

• Lungs CTAB

• No edema

EKG #1

1/22/2018

4

Labs #1

136

4.1

105

22

10

1.0118

Calcium 8.7

Magnesium 2.0

NT-proBNP 58

Troponin I <0.017

8.412.9

38.6

293Lactate 1.6

D-dimer 5.09Diff:

PMN’s 65%

Lymph’s 26%

Echo #1

1/22/2018

5

Questions

• 1. Classify this patients PE:

a) Massive

b) Submassive

c) Low-risk

Questions

• 2. How would you treat this patients PE?

a) Heparin

b) LMWH

c) Systemic thrombolysis

d) Catheter-directed thrombolysis

e) Embolectomy

1/22/2018

6

Case #2

• 74yo m

• Cardiac arrest x 10

min

• Non-shockable

• COPD, CAD, HTN,

CKD, PAD & DVT

EKG #2

1/22/2018

7

Labs #2

136

6.1

98

23

30

2.8124

Calcium 8.6

Magnesium 1.9

NT-proBNP 15,970

Troponin I 0.060

10.18.3

27.2

238ABG:

pH 7.3

pCO2 55

pO2 377

Lactate 8.1

Diff:

PMN’s 65%

Lymph’s 26%

Echo #2

1/22/2018

8

Echo #2: TAPSE

Echo #2: Tricuspid Regurg

1/22/2018

9

Questions

• 1. Classify this patients PE:

a) Massive

b) Submassive

c) Low-risk

Questions

• 2. How would you treat this patients PE?

a) Heparin

b) LMWH

c) Systemic thrombolysis

d) Catheter-directed thrombolysis

e) Embolectomy

1/22/2018

10

Objectives

• Understand hemodynamic principles of providing optimal

supportive care & risk-stratifying patients with PE

1. Reduce PVR

2. Optimize RV preload

3. Increase afterload

4. Improve RV systolic function

5. Avoid intubation

• Have your mind blown!

• Hint: it has nothing to do with t-PA!

Definitions: Intermediate-High Risk

• Massive PE:

• Pulmonary embolism in

a pt with persistent

hypotension or shock

• Submassive PE:

• Pulmonary embolism in

normotensive pt with

signs of Right Ventricular

strain/failure

1/22/2018

11

Size is not Everything

• Traditional thinking:

• Massive: >50%

pulmonary vascular bed

• Contemporary thought:

• Outcome & risk:

1. Clot burden

2. Cardiopulmonary

reserve

Wood et al. Chest 2002

Submassive PE

Massive PE

1/22/2018

12

Who is High Risk?

• Hypotension or shock

• 3x-7x mortality increase

• Normotensive patients (relative

importance):

• SpO2<95% (100)

• Substernal CP (76.5)

• HR>96 (34.6)

• Shock index>0.9 (19.7)

• RR>22 (17.1)

• Syncope

Kline et al. Am J Med ’03

Biomarkers

• BNP: Kucher et al. Circ ‘03

• 73 consecutive pts with acute PE

• 20 pts w/ adverse clinical events, median BNP 194.2 vs 39.1 in pts w/o

• Discriminatory level 90 (OR 8.0)

• Troponin: Kline et al ‘06

• 10/51 pts w/ adverse outcome had + troponin

• Sensitivity 20%

• Specificity 92%

• High NPV in hosp-death

1/22/2018

13

Electrocardiography (not just

S1Q3T3)

• Comparison ECG vs TTE:

• RBBB

• S1Q3 +/- T3

• TWI V1-V3

• 130/386 pts with RV strain:

• 12/386 (3%) died during

hospitalization, 8 with RV

strain (p=0.025)

Vanni S et al. Am J Med ‘09

Echocardiography

• 30-day deaths:

– Right heart failure

• 2 small cohort studies:

PPV 4% & 5%

• ICOPER, RV hypokinesis

– 1035 pts SBP>90, echo

within 24h

– 405pts w/ RV hypokinesis

– 30 day mortality:

-9% w/ RV hypokinesis

• -3.6% in pts w/o

hypokinesis

Kucher N et al. Arch Int Med ‘05

1/22/2018

14

1/22/2018

15

1/22/2018

16

High Risk Features1. Hypoxemia (SpO2

<95%)

2. ECG:

i. RBBB

ii. S1Q3T3

iii. T wave inversions

(anterior/inferior)

3. Elevated troponin

4. Elevated BNP

5. Abnormal Echo:

i. RV dilation (RV:LV>1.0)

ii. RV hypokinesis

iii. Paradoxical Septal

motion (D-sign)

iv. Tricuspid Regurgitation

v. TAPSE (<17mm)

EKG + Echo

Vanni S et al. Am J Med ‘09

1/22/2018

17

Complexities of the RV

Wood et al. Chest ‘02

RV Death Spiral

Marti et al Eur Heart J 2014

1/22/2018

18

Management Principles

• 1. Clot

Dissolution/Extraction

I. Systemic thrombolysis

II. Directed thrombolysis

III. Mechanical retrieval

IV. Embolectomy

• 2. Hemodynamic

Support

I. Pulmonary Vascular

resistance

II. Preload

III. Afterload

IV. Contractility

Management Principles

• 1. Hemodynamic

Support

I. Pulmonary Vascular

resistance

II. Preload

III. Afterload

IV. Contractility

• 2. Clot

Dissolution/Extraction

I. Systemic thrombolysis

II. Directed thrombolysis

III. Mechanical retrieval

IV. Thrombectomy

1/22/2018

19

Hemodynamic Support

1. Decrease Pulmonary

Vascular Resistance

2. Optimize LV preload

3. Increase LV afterload

4. Improve RV

Contractility Wood et al. Chest 2002

RV Exquisitely Sensitive to Afterload

Friedman 2014.

1/22/2018

20

Wood et al. Chest 2002

RV CO = LV CO

Remember the Septum

Pulmonary Vascular Resistance

1. High pCO2/low pH in

pulmonary artery

2. Low mixed venous O2

(SVO2)

3. High sympathetic

tone: α-receptor

agonism

4. High plateau

pressures

5. * Endothelial injury

6. Hypoxic

vasoconstriction

7. Micro- &

Macrothrombosis

1/22/2018

21

Decrease Pulmonary Vascular Resistance

• Relieving Obstruction:

• THE CLOT

• Neurohumoral effects

• Thromboxane A2

• Platelet activating factor

• Serotonin

• C3a, C5a, thrombin

Inhaled Nitric Oxide• Weak evidence

• cGMP pathway smooth

muscle relaxation

1. Vasodilation

2. Bronchodilation

3. Antiinflammatory effect

• 10-20ppm

• Improves V/Q mismatch

• Reduce shunting

1/22/2018

22

Kline et al. BMJ 2014.

Addressing the Clot

1. Systemic

Thrombolysis

2. Cather-directed:

i. Lysis

ii. Extraction

3. Surgery:

i. Embolectomy

1/22/2018

23

The Modern Era (post-2012)

• MOPETT: ½ dose t-PA submassive PE

– RV dysfunction resolved

– Almost no bleeding

• TOPCOAT: tenecteplase

– Stopped early, composite endpoint

– Global health assessment improved

• PEITHO: tenecteplase

– 1000 pts; “great caution”; composite endpoint

– NNT: 33 & NNH: 55

SEATTLE II Study

1/22/2018

24

SEATTLE II

Seattle II: Conclusions

• Safe:

– 0 ICH’s

• Early hemodynamic

improvement

• Worthy of further study

• Submassive PE pts die

infrequently

1/22/2018

25

Hemodynamic Support


Vascular Resistance



4. Improve RV


2. Optimize LV Preload

• Volume loading:

• CAUTION

• Mercat et al. Crit Care

Med 1999.

• N=13, C.I. <2.5L/min/m2

• 500mL IV dextran

• Δ C.I. inversely related to

RVEDV

1/22/2018

26

Diuretics?!?!

Really doctor, diuretics?

• Nonrandomized

• Retrospective

• Submassive PE

• N=70

• Physician discretion

• Lasix 40mg

– Repeat q4h if urine o/p

<0.5ml/kg

1/22/2018

27

Ternacle et al. ‘14

• Endpoints:

– Echocardiographic

improvement

– Shock index

– PESI

Lasix (n=40)

Normal Saline (n=30)

Troponin elevation

70% 64%

NT-proBNP

77% 67%

LVEF 57% 58%

Meandose

78+/-42mg 1.6+/-0.9L


1/22/2018

28


Airway Management

• Avoid Intubation

• If possible

• afterload (meds)

• preload to RV & LV

• pulmonary vascular

resistance (PPV)

• All hands on deck:

• pressors

1/22/2018

29

Hemodynamic Support


Vascular Resistance



4. Improve RV


3. Increase LV Afterload

• Goal: optimize perfusion to RV through RCA

• Limit RV ischemia

• RV CPP= MAP – RV Pressure

• RV Pressure = PA pressure

• Vasopressors:

• afterload

• venous return

1/22/2018

30

RV Exquisitely Sensitive to Afterload

Friedman 2014.

LV perfused in DiastoleRV perfused in Diastole & Systole

1/22/2018

31

Vasopressors

DrugCardiac Output

Pulmonary Vascular

Resistance

Systemic Vascular

Resistance

Norepinephrine + +/- ++

Phenylephrine - + +

Vasopressin - - ++

Epinephrine ++ - +

Hemodynamic Support


Vascular Resistance



4. Improve RV


1/22/2018

32

Septal Dyskineisa

Septal Dyskinesia

1/22/2018

33

Tricuspid Regurgitation

Tricuspid Regurgitation

1/22/2018

34

TAPSE- RV hypokinesis

4. Improve RV Contractility

• After BP improves

1. Dobutamine

• Max 5μg/kg/min

• Synergistic with iNO

• Low CO state:

• Cool, low ScVo2, narrow

pulse pressure

1/22/2018

35

Inotropes

DrugCardiac Output

PulmonaryVascular

Resistance

Systemic Vascular

Resistance

Dobutamine ++ - -

Epinephrine ++ +/- ++

Milrinone ++ - -

Dopamine + +/- +

VA ECMO

1/22/2018

36

Summary

• Post-diagnosis risk

stratification:

• Biomarkers, echo, EKG,

hypoxemia, BP

• Aggressive early or watch and

wait?

• Mortality low

• To lyse or not to lyse?

• Weak data

• Hemodynamic Optimization:

1. Reduce pulmonary vascular

resistance (iNO)

2. Don’t worsen the preload

3. Increase systemic vascular

resistance (NE)

4. Increase RV contractility

• YOU can make the difference

• Catch-up Phenomenon

References

• Levine, M et al. A Randomized Trial of a Single Bolus Dosage Regimen of Recombinant Tissue Plasminogen Activator in Patients with Acute Pulmonary Embolism. Chest 96; 6,

December 1990:1473-1479

• Tibbutt, DA, et al. Comparison by Controlled Clinical Trial of Streptokinase and Heparin in Treatment of Life-threatening Pulmonary Embolism. British Medical Journal, 1974, 1, 343-347

• The Urokinase Pulmonary Embolism Trial: a national cooperative study. Circulation 1973; 47(supp): II1-II108

• Dalla-Volta S, et al. PAIMS-2: Alteplase Combined With Heparin Versus Heparin in Treatment of Acute Pulmonary Embolism. Plasminogen Activator Italian Multicenter Study 2. Journal

of American College of Cardiology 1992;20:520-6

• Kline JA, et al. Tenecteplase to treat pulmonary embolism in the emergency department. Journal of Thrombosis and Thrombolysis (2007) 23:101-105

• Goldhaber SZ, et al. Alteplase versus heparin in acute pulmonary embolism: a randomized trial assessing right-ventricular function and pulmonary perfusion. Lancet 1993; 341:507-511.

• Konstantinides S. et al. Heparin Pluse Alteplase Compared with Heparin Alone in Patients with Submassive Pulmonary Embolism. New England Journal of Medicine, vol. 347, no. 15, Oct

10, 2002; 1143-1150

• PIOPED Investigators. Tissue plasminogen activator for the treatment of acute pulmonary embolism: a collaborative study by the PIOPED Investigators. Chest 1990; 97:528-533

• Worster, A et al. Thrombolytic Therapy for Submassive Pulmonary Embolism? Annals of Emergency Medicine. 2007, vol 50; no. 1:78-84

• Come, PC. Echocardiographic Evaluation of Pulmonary Embolism and Its response to Therapeutic Interventions. Chest 101, 4, April 1992; 151S-162S.

• Todd, JL, et al. Thrombolytic Therapy for Acute Pulmonary Embolism: A Critical Appraisal. Chest. 135/5/ May 2009; 1321-1329

• Kline et al. Pulse Oximetry to Predict In-Hospital Complications from Pulmonary Embolism. The American Journal of Medicine. August 15, 2003. Volume 115

• Kucher, N. et al. Prognostic Role of Brain Naturietic Peptide in Acute Pulmonary Embolism. Circulation. 2003; 107; 2545-2547

• Caldicott D, et al. Case Report: Tenecteplase for Massive Pulmonary Embolus. Resuscitation 55 (2002) 211-213.

1/22/2018

37

References

• Vanni, S. et al. Prognostic Value of ECG Among Patients with Acute Pulmonary Embolism and Normal Blood Pressure. The American Journal of Medicine, vol. 122, No. 3, March 2009

• Kucher, N. et al. Prognostic Role of Echocardiography Among Patients with Acute Pulmonary Embolism and a Systolic Arterial Pressure of 90mm Hg or Higher. Archives of Internal

Medicine. 2005; vol 165; Aug 8/22

• Konstantinides S, et al. Comparison of Alteplase Versus Heparin for Resolution of Major Pulmonary Embolism. American Journal of Cardiology. 1998; 82:966-970

• Goldhaber SZ et al. Acute Pulmonary Embolism: Clinical Outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet vol. 353, April 24 1999; 1386-1389

• Konstantinides S. Clinical Practice: Acute Pulmonary Embolism. The New England Journal of Medicine 359;26, December 25 th 2008. 2804-2813.

• Meneveau, N, et al. In-hospital and Long-term Outcome After Submassive and Massive Pulmonary Embolism Submitted to Thrombolytic Therapy. European heart Journal (2003) 24,

1447-1454

• Stevinson BG, et al. Echocardiographic and Functional Cardiopulmonary Problems 6 Months after First-time Pulmonary Embolism in Previously Healthy Patients. European Heart

Journal (2007) 28, 2517-2524.

• Kline JA, et al. Surrogate Markers for Adverse Outcomes in Normotensive Patients with Pulmonary Embolism. Critical Care Medicine. 2006, vol. 34, no. 11;2773-2780

• Becattini C, et al. Bolus Tenecteplase for Right Ventricle Dysfunction in Hemodynamically Stable Patients with Pulmonary Embolism. Thrombosis Research 125 (2010) e82-e86.

• Miniati M, et al. Value of Transthoracic Echocardiography in the Diagnosis of Pulmonary Embolism: Rsults of a Prospective Study in Unselected Patients. The American Journal of

Medicine. May 2001, vol. 110;528-535

• Kucher N, et al. Incremental Prognostic Value of Troponin I and Echocardiography in Patients with Acute Pulmonary Embolism. European Heart Journal (2003) 24;1651-1656

• Tebbe U, et al. Desmoteplase in Acute Massive Pulmonary Thromboembolism. Thrombosis and Haemostasis. 2009; 101:557-562

• Kline JA, et al. Prospective Evaluation of Right Ventricular Function and Functional Status 6 Months after Acute Submassive Pulmonary Embolism. Chest 2009; 136:1202-1210

• Kucher N and Goldhaber SZ. Cardiac Biomarkers for Risk Stratification of Patients with Acute Pulmonary Embolism. Circulation. 2003; 108:2191-2194

Documents

Right Heart Strain in Life- Threatening Pulmonary Embolism · 2018-01-22 · 1/22/2018 1 Right Heart Strain in Life-Threatening Pulmonary Embolism Mark Favot, MD, FACEP Assistant