Case PresentationCase Presentation

• 45f acute CP, dyspnea, near-syncope• Pale, diaphoretic, looks unwell• Afebrile, HR 110, RR 32, BP 118/68• Sats 75% RA, 92% on NRB• JVP elevated• HS Normal• Chest clear

• 45f acute CP, dyspnea, near-syncope• Pale, diaphoretic, looks unwell• Afebrile, HR 110, RR 32, BP 118/68• Sats 75% RA, 92% on NRB• JVP elevated• HS Normal• Chest clear

Portable CXRPortable CXR

ECGECG

Next?Next?

ECHOECHO

• Significant RV dilation• Increased R sided pressures• RV hypokinesis • Clot visible in RV

• Significant RV dilation• Increased R sided pressures• RV hypokinesis • Clot visible in RV

CT-pulmonary angiogramCT-pulmonary angiogram

ManagementManagement

• Heparin PE protocol initiated• Colleague asks why you haven’t

thrombolysed yet

“But she’s not in shock!”“Yeah, but she’s a submassive PE”“…what’s a submassive PE?”

• Heparin PE protocol initiated• Colleague asks why you haven’t

thrombolysed yet

“But she’s not in shock!”“Yeah, but she’s a submassive PE”“…what’s a submassive PE?”

Thrombolysis of the Submassive PE

Thrombolysis of the Submassive PEMichael Kenney MD CCFP(EM)Dept of Emergency Medicine

University of Calgary

Michael Kenney MD CCFP(EM)Dept of Emergency Medicine

University of Calgary

ObjectivesObjectives1. Define submassive PE2. Discuss clinical significance of a

submassive PE3. Determine an evidence-based approach

to identifying the SMPE4. Review the literature regarding efficacy of

thrombolytics in SMPE5. Review contraindications to thrombolytics

in PE6. Local expert opinion on alternate therapy

1. Define submassive PE2. Discuss clinical significance of a

submassive PE3. Determine an evidence-based approach

to identifying the SMPE4. Review the literature regarding efficacy of

thrombolytics in SMPE5. Review contraindications to thrombolytics

in PE6. Local expert opinion on alternate therapy

Massive PEMassive PE

• Pulmonary embolism in the setting of hemodynamic instability (SBP<90)

PE + Shock = Massive PE

• Literature supports thrombolytics

(Kearon et al, Chest 2008)

• Pulmonary embolism in the setting of hemodynamic instability (SBP<90)

PE + Shock = Massive PE

• Literature supports thrombolytics

(Kearon et al, Chest 2008)

Submassive PE (SMPE)Submassive PE (SMPE)

• Pulmonary embolism in the setting of a hemodynamically stable patient with ECHO-proven evidence of right ventricular dysfunction

PE + NBP + RV dysfunction = SMPE

• Pulmonary embolism in the setting of a hemodynamically stable patient with ECHO-proven evidence of right ventricular dysfunction

PE + NBP + RV dysfunction = SMPE

ECHO in Submassive PEECHO in Submassive PE

• RV hypokinesis • RV dilation• Pulmonary hypertension >30mmHg

• Septal shift > RV hypokinesis > RV dilation

(Wolde et al, Arch Int Med 2004; Kline et al, Am Heart

Journal, 2008)

• RV hypokinesis • RV dilation• Pulmonary hypertension >30mmHg

• Septal shift > RV hypokinesis > RV dilation

(Wolde et al, Arch Int Med 2004; Kline et al, Am Heart

Journal, 2008)

ECG Strain RV Dysfunction

ECG Strain RV Dysfunction

Clinical SignificanceClinical Significance

• When compared to patients with PE and normal RV function– Higher mortality (8-13%)– Higher in-hospital complications– Higher long-term cardiopulmonary morbidity

• Pulm hypertension• R CHF

( Kreit et al, Chest 2005)

• When compared to patients with PE and normal RV function– Higher mortality (8-13%)– Higher in-hospital complications– Higher long-term cardiopulmonary morbidity

• Pulm hypertension• R CHF

( Kreit et al, Chest 2005)

PathophysiologyPathophysiology

Identifying the SMPEIdentifying the SMPE

1. Clinical2. ECG3. Cardiac biomarkers• Troponins• BNP

4. CT Scan

1. Clinical2. ECG3. Cardiac biomarkers• Troponins• BNP

4. CT Scan

Clinical Clues Clinical Clues

• Syncope• Significant tachycardia• Significant hypoxia• P/E

– JVD– Parasternal heave– Split P2– TR murmur

• Syncope• Significant tachycardia• Significant hypoxia• P/E

– JVD– Parasternal heave– Split P2– TR murmur

ECG in SMPEECG in SMPE

• Strain pattern (T inversion V1-V4)*• S1-Q3-T3• RAD• RBBB

• Insensitive and mostly non-specific• Strain pattern specific for RV strain

RV dysfunction

• Strain pattern (T inversion V1-V4)*• S1-Q3-T3• RAD• RBBB

• Insensitive and mostly non-specific• Strain pattern specific for RV strain

RV dysfunction

Cardiac MarkersCardiac Markers

• Troponins• BNP

• Troponins• BNP

Cardiac MarkersCardiac Markers• Troponins

– Correlates with presence of RV dysfunction

– Predictive of complicated in-hospital course

– Associated with increased mortality in setting of PE

– NPV 93-97% for 30 day mortality

(Konstantinides, Circulation 2002; La Vecchia et al Heart, 2005; Askey et al, Am J or Emer Med 2007)

• Troponins– Correlates with presence of RV

dysfunction– Predictive of complicated in-hospital

course– Associated with increased mortality in

setting of PE – NPV 93-97% for 30 day mortality

(Konstantinides, Circulation 2002; La Vecchia et al Heart, 2005; Askey et al, Am J or Emer Med 2007)

Cardiac MarkersCardiac Markers• BNP

– Correlates with RV dysfunction– 95-99% NPV for complicated in-

hospital course– Predictive of elevated 30 day mortality– Significantly predicted greater dyspnea

at rest, decreased exercise tolerance at 6 months

(Wolde et al, Circulation, 2003; Binder, Circulation 2005; Kline et al, Am Heart Journal, 2008)

• BNP– Correlates with RV dysfunction– 95-99% NPV for complicated in-

hospital course– Predictive of elevated 30 day mortality– Significantly predicted greater dyspnea

at rest, decreased exercise tolerance at 6 months

(Wolde et al, Circulation, 2003; Binder, Circulation 2005; Kline et al, Am Heart Journal, 2008)

Cardiac MarkersCardiac Markers

• Negative markers = lower risk, more favorable course

• Positive markers = ECHO

• Use clinical judgement• Serial testing

• Negative markers = lower risk, more favorable course

• Positive markers = ECHO

• Use clinical judgement• Serial testing

CT ScanCT Scan

• RV enlargement on the CT angiogram defined as RV diameter >90% LV diameter, appears to be an independent risk factor for death and nonfatal clinical complications

(Kucher et al, Circulation, 2006; Schoepf et al Circulation, 2005)

• RV enlargement on the CT angiogram defined as RV diameter >90% LV diameter, appears to be an independent risk factor for death and nonfatal clinical complications

(Kucher et al, Circulation, 2006; Schoepf et al Circulation, 2005)

ED assessment of the Hemodynamically Stable

PE

ED assessment of the Hemodynamically Stable

PE

TherapyTherapy

1. Anticoagulation (heparin)2. Thrombolytic therapy

1. Efficacy2. Choice of agent3. Absolute Contraindications4. Risk factors for Major Bleeding

3. Catheter embolectomy4. Surgical embolectomy

1. Anticoagulation (heparin)2. Thrombolytic therapy

1. Efficacy2. Choice of agent3. Absolute Contraindications4. Risk factors for Major Bleeding

3. Catheter embolectomy4. Surgical embolectomy

Efficacy of Thrombolytics in SMPE

Efficacy of Thrombolytics in SMPE

The Literature– <800 patients overall – Not all randomized controlled– Some studies lysed all PE’s – SMPE not consistently defined– UK, SK, tPA

The Literature– <800 patients overall – Not all randomized controlled– Some studies lysed all PE’s – SMPE not consistently defined– UK, SK, tPA

Efficacy of Thrombolytics in SMPE

Efficacy of Thrombolytics in SMPE

Cardiopulmonary Physiology– Markedly improves PAP, RV function

and pulmonary perfusion– Only one study long-term

• benefit persists @ 7years

Cardiopulmonary Physiology– Markedly improves PAP, RV function

and pulmonary perfusion– Only one study long-term

• benefit persists @ 7years

Efficacy of Thrombolyitics in SMPE

Efficacy of Thrombolyitics in SMPE

Clinical Outcome Measures– Lower inhospital complication

•Fewer recurrent PE•Less use of vasopressors, intubation,

rescue embolectomy– Trends toward improved mortality– No study or meta-analysis large enough

to clearly show mortality benefit

Clinical Outcome Measures– Lower inhospital complication

•Fewer recurrent PE•Less use of vasopressors, intubation,

rescue embolectomy– Trends toward improved mortality– No study or meta-analysis large enough

to clearly show mortality benefit

Major BleedMajor Bleed

1. Intracranial Hemorrhage2. Any bleed leading to shock

– GI and retroperitoneal most common

3. Any bleed leading to transfusion > 2U PRBCs or surgery

1. Intracranial Hemorrhage2. Any bleed leading to shock

– GI and retroperitoneal most common

3. Any bleed leading to transfusion > 2U PRBCs or surgery

ContraindicationsContraindications

Absolute• Hx of hemorrhagic CVA• Active intracranial neoplasm• Recent (<2 months) intracranial surgery

or trauma• Recent (<2 weeks) major GI bleed or

major surgery

Tapson et al, Chest, Oct 2008

Absolute• Hx of hemorrhagic CVA• Active intracranial neoplasm• Recent (<2 months) intracranial surgery

or trauma• Recent (<2 weeks) major GI bleed or

major surgery

Tapson et al, Chest, Oct 2008

Risk Factors for ICHRisk Factors for ICH• Age > 70• Female• Weight < 70kg• SBP >170 or DBP >95• PHx ischemic CVA• DM• Elevated INR• PLT < 100

RF 0-1 = 0.5-1% 2-4 = 2.5% >5 = 4%

• Age > 70• Female• Weight < 70kg• SBP >170 or DBP >95• PHx ischemic CVA• DM• Elevated INR• PLT < 100

RF 0-1 = 0.5-1% 2-4 = 2.5% >5 = 4%

Thrombolytics cause Intracranial Hemorrhage

Thrombolytics cause Intracranial Hemorrhage

1%1%

Choice of ThrombolyticChoice of Thrombolytic

• tPA only lytic approved• tPA 100mg

– 10mg bolus, remaining 90mg over 2 hours– most widely studied and accepted in PE

• TNK has not been studied adequately in PE– 0.5mg/kg (50mg max)– One study 22 patients, equivalent to tPA

• tPA only lytic approved• tPA 100mg

– 10mg bolus, remaining 90mg over 2 hours– most widely studied and accepted in PE

• TNK has not been studied adequately in PE– 0.5mg/kg (50mg max)– One study 22 patients, equivalent to tPA

Bottom Line of Thrombolytics in SMPE

Bottom Line of Thrombolytics in SMPE

• tPA• Trends but no definitive mortality

benefit in SMPE• Case-by-case, not routine• Benefit vs bleeding risk

assessment• Involve intensivist early• Involve patient and family

• tPA• Trends but no definitive mortality

benefit in SMPE• Case-by-case, not routine• Benefit vs bleeding risk

assessment• Involve intensivist early• Involve patient and family

EmbolectomyEmbolectomy

• Percutaneous Catheter Extraction– Pigtail rotational catheter– Usually tPA in addition– May take hours– Angiojet coming

• Surgical Embolectomy– Rare benefit over percutaneous – If absolute contraindications and IR unable

• Percutaneous Catheter Extraction– Pigtail rotational catheter– Usually tPA in addition– May take hours– Angiojet coming

• Surgical Embolectomy– Rare benefit over percutaneous – If absolute contraindications and IR unable

IVC Filter PlacementIVC Filter Placement

• Reduces short term risk of recurrent PE

• Consider in PE– Little cardiac reserve– Significant extremity clot burden– Contraindications to lytics, or high

risk for bleeding

• Reduces short term risk of recurrent PE

• Consider in PE– Little cardiac reserve– Significant extremity clot burden– Contraindications to lytics, or high

risk for bleeding

SummarySummary Submassive PE = normal BP +

RVD Significant morbidity and mortality

associated Reviewed clinical clues, ECG

findings, and cardiac markers helpful in identifying the patient with SMPE

ECHO if RV dysunction suspected

Submassive PE = normal BP + RVD

Significant morbidity and mortality associated

Reviewed clinical clues, ECG findings, and cardiac markers helpful in identifying the patient with SMPE

ECHO if RV dysunction suspected

SummarySummary Thrombolytics

• improve cardiopulmonary hemodynamics

• lower in-hospital complications• Trends, but no clear mortality benefit

Reviewed absolute contraindications and risk factors for major bleed

Discussed non-medical therapeutic options

Thrombolytics• improve cardiopulmonary

hemodynamics• lower in-hospital complications• Trends, but no clear mortality benefit

Reviewed absolute contraindications and risk factors for major bleed

Discussed non-medical therapeutic options

Questions?Questions?