1. A.Postadzhiyan, MD, PhD St Anna University Hospital, Sofia, Bulgaria
Pulmonary embolism
A.Postadzhiyan, MD, PhD
St Anna University Hospital, Sofia, Bulgaria

2. The problem

3. Treatment Anticoagulation (UFH, LMWH, Fondaparinux)
Systemic thrombolysis
Catheter-directed thrombolysis
Mechanical and pharmacomechanical interventions
Surgical embolectomy

4. Standard of care for PE

5. Patient risk stratification (per AHA 2011 guidelines)
Pulmonary Embolism
Patient risk stratification (per AHA 2011 guidelines)
Massive PE
Submassive PE
Minor/Nonmassive PE
High risk
Moderate risk
Low risk
Sustained hypotension (systolic BP <90 mmHg for 15 min)
Inotropic support
Pulselessness
Persistent profound bradycardia (HR <40 bpm with signs or symptoms of shock)
Systemically normotensive (systolic BP 90 mmHg)
RV dysfunction
Myocardial necrosis
No RV dysfunction
No myocardial necrosis

6. “Saddle PE” - AngioVac

7. Patient risk stratification (per AHA 2011 guidelines)
Pulmonary Embolism
Patient risk stratification (per AHA 2011 guidelines)
Massive PE
Submassive PE
Minor/Nonmassive PE
High risk
Moderate risk
Low risk
Sustained hypotension (systolic BP <90 mmHg for 15 min)
Inotropic support
Pulselessness
Persistent profound bradycardia (HR <40 bpm with signs or symptoms of shock)
Systemically normotensive (systolic BP 90 mmHg)
RV dysfunction
Myocardial necrosis
No RV dysfunction
No myocardial necrosis

8. Thrombolytic Therapy
Circulation. 2005;112:e28-e32

9. Kadner et al. J Thorac Cardiovasc Surg. 2008 Aug;136(2):448-51.
Premise for use of CDT
Systemic lysis
8% Fail Lytics
33% have contraindications for lytics
Bleeding risks
Surgical Therapy for Massive and Submassive PE
Low study numbers in recent literature n = 25-47
Mortality 6-8%
Should be considered if local expertise available
MAPPET JACC 30(5) 1997,
Kadner et al. J Thorac Cardiovasc Surg Aug;136(2):

10. Mechanical Fragmentation
Catheter Techniques: “Pharmacomechanical” Therapy Rapidly achieve central clot debulking to improve pulmonary perfusion
Mechanical Fragmentation
Hydrodynamic
Ultrasound-Accelerated Fibrinolysis
Suction Embolectomy

11. Results with CDT (“success” without vs with limited lytic)
Jaff MR, McMurtry MS, et al. Circulation 2011, 123: , p 1799
Summary of review of reports on CDT treatment of 348 pts with massive PE.
Technique
Without Lytic
With Lytic
Aspiration
81%
100%
Fragmentation
82%
90%
Rheolytic
75%
91%
New
??%
Some lytic good, even better if prolonged.
Lower dose associated with less bleeding.

12. Heparin vs Lysis (for Massive PE)
Lysis >> Heparin (despite ACCP opposition)
Restoration of lung 24 hrs
30-35%  if Rx with lysis
Interventional better? Probably, but more data needed.
0.05% if Rx with heparin
But, BOTH 7 days.
So, ACCP says no to Lysis unless death imminent.
Recurrent PE/DEATH
19% if Rx with heparin alone
9.4% if Rx with lytic
??% if Interventional Rx (CDT)  Need data
Potentially BIG ROLE, especially if safer.
Wan et al. Circulation. 2004; 110:

13. Patient risk stratification (per AHA 2011 guidelines)
Pulmonary Embolism
Patient risk stratification (per AHA 2011 guidelines)
Massive PE
Submassive PE
Minor/Nonmassive PE
High risk
Moderate risk
Low risk
Sustained hypotension (systolic BP <90 mmHg for 15 min)
Inotropic support
Pulselessness
Persistent profound bradycardia (HR <40 bpm with signs or symptoms of shock)
Systemically normotensive (systolic BP 90 mmHg)
RV dysfunction
Myocardial necrosis
No RV dysfunction
No myocardial necrosis
RV dysfunction
RV/LV ratio > 0.9 or RV systolic dysfunction on echo
RV/LV ratio > 0.9 on CT
Elevation of BNP (>90 pg/mL)
Elevation of NTpro-BNP (>500 pg/mL)
ECG changes
new complete or incomplete RBBB
anteroseptal ST elevation or depression
anteroseptal T-wave inversion

14. Adverse event rate: 54% if RVD/LVD ratio < 0.9
Patients with right heart dysfunction defined as RVD/LVD > 0.9 have a significantly higher chance of adverse events within 30 days.
Quiroz R, Kucher N, Schoepf J, et. al. Circulation. 2004;109:
Adverse event rate:
54% if RVD/LVD ratio < 0.9
82% if RVD/LVD ratio ≥ 0.9
OR : (p=0.041)

15. PE related mortality rate at 3 years:
PE patients with right ventricle dysfunction (RVD) unresolved prior to discharge suffered 3-times the mortality rate than patients whose RVD was resolved
Grifoni S, Vanni S, Magazzini S, et al. Arch Intern Med 2006; 166:
PE related mortality rate at 3 years:
13.3% if RVD unresolved at discharge
4.4% if RVD resolved at discharge

16. Pulmonary Embolism-3 Trial: Heparin plus Alteplase Compared with Heparin Alone in Patients with Submassive Pulmonary Embolism
Konstantinides et al. N Engl J Med 2002; 347:

17. Heparin vs Lysis (for Submassive PE)
Mortality
3.0% if Rx with Heparin
<1.0% if Rx with IV lysis
Hard for Interventional to make a BIG improvement
Prob better to differences in long term
Persistent RV dysfunction
Chronic thromboembolic pulmonary hypertension
(CTEPH)
Impaired Quality of Life

18. Pulm HTN and Submassive PE
118 treated with heparin alone
21 worsened and received lytic
F/U = 180 survivors of which 162 evaluated (90%)
Heparin alone Lytic
RVSP > 40 at diag 35% 61%
6 mo RVSP > baseline 27% 0%
6 mo NYHA class > 3 46%
in pts with elevation
Kline et al. Chest Nov;136(5):

19. Recommendations for Catheter Embolectomy and Fragmentation for PE
Level of Evidence
Depending on local expertise, either catheter embolectomy and fragmentation or surgical embolectomy is reasonable for patients with massive PE and contraindications to fibrinolysis
Class IIa; Level of Evidence C
Catheter embolectomy and fragmentation or surgical embolectomy is reasonable for patients with massive PE who remain unstable after receiving fibrinolysis
For patients with massive PE who cannot receive fibrinolysis or who remain unstable after fibrinolysis, it is reasonable to consider transfer to an institution
experienced in either catheter embolectomy or surgical embolectomy if these procedures are not available locally and safe transfer can be achieved
Either catheter embolectomy or surgical embolectomy may be considered for patients with submassive acute PE judged to have clinical evidence of adverse prognosis (new hemodynamic instability, worsening respiratory failure, severe RV dysfunction, or major myocardial necrosis)
Class IIb; Level of Evidence C
Catheter embolectomy and surgical thrombectomy are not recommended for patients with low-risk PE or submassive acute PE with minor RV dysfunction, minor myocardial necrosis, and no clinical worsening
Class III; Level of Evidence C
Circulation 2011, 123:

21. The Ekosonic Endovascular System with Mach4e rapid pulse modulation
Lower energy US dissociate fibrin strands to allow more effective thrombolysis with shorter and lower dose administration
5.4 fr Intelligent side-hole drug delivery catheter
Ultrasound-assisted catheter-directed thrombolysis is administered with the aide of the EKOS catheter. A, The console, the catheter with multiple side-holes, and the ultrasound-emitting fiber. B, The catheter is placed in the right and left lung. Note the multiple ultrasound emitters along the length of the catheter (arrow
Filament with multiple US transducers 21

23. The SEATTLE II Trial
Submassive and massive pulmonary Embolism treatment with ultrasound AccleraTed ThromboLysis thErapy
SEATTLE II (Single-arm, prospective)
Purpose:
Determine if EKOS therapy will decrease the ratio of RV to LV within 486 hours in patients with massive or submassive PE
Treatment:
24 mg of rt-PA delivered through the EkoSonic Endovascular System
Primary Outcome measures:
RV/LV diameter ratio (baseline and 486 after baseline)
Major bleeding (within 72 hours of treatment initiation)

24. Our Anecdotal Experience
N = 50 patients in last 5 years
High risk markers, echo, troponin,
Ultrasound guided access of vein
Tromfragmentation +/- thrombaspiration with 8 f PTCA guiding catheter
Half dose lythic Tx
Results
average drop of the heart rate form 107 bpm to 88 bpm
SaO2 has increased from 90 up to 94%
the systolic pressure in the pulmonary artery dropped to 51 mmHg from 77 mmHg
the systolic arterial pressure has increased to 105 mmHg from 89 mmHg.
No in-hospital and 30-day mortality
Mean hospital stay 5 days

25. If in patients with massive or high risk submassive PE we adopt the same strategy as in ACS with an early diagnosis and more aggressive Tx what will be the impact of short and long term prognosis ?

26. Cardiac cathlab provides a proper environment for such procedures – all the necessary equipment and trained staff are already there
Cost and time – similar with the average for a PTCA in ACS