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Egyptian Society of Chest Diseases & Tuberculosis The 55 th International Conference 25-28 March 2014 Cairo, Egypt. Treatment of submassive pulmonary embolism Is thrombolysis the best treatment??. Majdy M Idrees Saudi Arabia. Gulf Thoracic Meeting Abu Dhabi, UAE MArch 18-20, 2010 . - PowerPoint PPT Presentation
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Treatment of submassive pulmonary embolism
Is thrombolysis the best treatment??
Gulf Thoracic MeetingAbu Dhabi, UAE
MArch 18-20, 2010
Egyptian Society of Chest Diseases & Tuberculosis The 55th International Conference
25-28 March 2014Cairo, Egypt
Majdy M IdreesSaudi Arabia
Financial disclosure
•Honoraria for lecturing for Actelion, BSP, pfizer, AstraZeneca, MSD & GSK
•Research grant from pfizer & Actelion
•Multi-national RCT sponsored by Actelion, BSP, and pfizer
The 55th ESCT conference
“Venous thrombosis is always a severe disease and is often fatal, because fragments of the thrombi may detach and occlude branches of the pulmonary artery... the occlusion of the main branches of the pulmonary artery causes a striking rise of the blood pressure in these vessels. This rise, which the right heart might fight in order to ensure circulation, may sometimes lead to cardiac arrest.”
Picot 1884 Lecons de Clinique Médicale
The 55th ESCT conference
“In acute diseases, coldness of the
extremities,,
“is a very bad sign”
The aphorisms of Hippocrates
The 55th ESCT conference
•74-year-old lady presented with progressive shortness of breath (WHO functional class IV) over 10-day period
•She had one attack of syncope 2 days before her presentation
•Recent surgery (appendectomy 3 weeks earlier)
The 55th ESCT conference
•BP 155/88, PR 92/min, O2 sat 84% on r/a and
92% on 4 L/min•Physical examination revealed Rt. heart strain
•Doppler US negative •EKG revealed sinus tachycardia with T wave
inversion in the anterior precordial leads•NT-pro BNP 4200
The 55th ESCT conference
Echocardiography:•Dilated RV•Severe TR
•sPAP 84 mmHg•Small posterior PE
The 55th ESCT conference
The 55th ESCT conference
CT angiogram..•PE occluding the
main right PA•RV:LV > 1
Management issues:
.1How severe is this patient’s PE?
.2What is the risk of mortality? Risk-stratifying
.3Is the pathobiology different from massive PE?
.4What is the “best” management approach?
The 55th ESCT conference
RV Dysfunction
SeverityEmbolism sizeCardiopulmonary Status
100
70
30
10
0
Mor
talit
ySudden Death
Cardiac Arrest
Shock
Outcome in pulmonary embolism
Infliction Point Our patient
Goldhaber 1993 23 2 8.7%
Grifoni 2000 61 3 5%
Hamel 2001 64 0 0%
Giannitsis 2000 26 2 7.7%
Viellard-Baron 2002 32 1 3%
Pruszczyk 2003 64 8 12.5%
Pruszczyk 2003 51 10 19.6%
Kucher 2003 19 2 10.5%
340 28 8.2%
Outcomes in hemodynamically-stable, RV-strained PE treated with Heparin
Study Year Number PE Death % Mortality
Massive Pulmonary EmbolismWell-understoodObstructive shock
Sub-massive Pulmonary Embolism
Poorly understood
Different pathophysiology
The 55th ESCT conference
Hemodynamic – PE
-10
0
10
20
120
100
80
60
40
m PAP
Progressive PR occlusion
RAP
Systemic Arterial Pressure
COP RV Pressure
Total OcclusionZero Occlusion
Pre
ssur
e (m
mH
g)
Guyton Cir Res 1954; 2:326-332
PE: Vascular resistance vs. obstruction
0 30
20
30
10
10 20 Miller index
PVR
•• • •
•••
•
•
••
•
°
°
°
°°
°
°
°•
•
••
•
•
••
•
••
Petitpretz Circ 1984; 70:861-866.
Thrombolytic therapy in massive PE
• Randomized trial• Aimed for 40 patients• Patients with massive PE (SBP<90)• IV bolus of SK Vs Heparin
The study was prematurely Terminated.
Throm Thrombolysis 1995
Sur
viva
l
0
20
40
60
80
100
Heparin
Streptokinase
4
Thrombolytic therapy in massive PE
J Throm Thrombolysis 1995
4
Conclusion:Although a small study, it strongly support the current indication for thrombolytic therapy in massive PE.
UPET ’73 Urokinase 73 73 2.7% (2) 8.2% (6)
Marini ’88 Urokinase 20 10 0% 0%
PIOPED ’90 rt-PA 9 4 11.1% (1) 0%
Levine ’90 rt-PA 33 25 3.0% (1) 0%
PAIMS 2 ’92 rt-PA 20 16 10% (2) 6.3% (1)
Goldhaber ’93 rt-PA 46 55 0% 3.6% (2)
Konstantinides ’02 rt-PA 118 138 3.4% (4) 2.2% (3)
Total 319 321 3.1% (10) 3.7% (12)
Non-shock mortality thrombolytic therapy
Study Lytic Heparin Lytic % (N) Heparin % (N)
Patients Mortality
American Journal of Cardiovascular Drugs 2004, 4(2):69-74
Thrombolytic therapy in patients with non-shock pulmonary embolism?
• Randomized, DB, multicenter trial• 256 pt• PE confirmed by HP V/Q scan, spiral CT or angiogram• Normal BP• RV dysfunction (echo, ECG or RHC)
Primary endpoint:• In-hospital mortality• Worsening circulation• Need for additional therapy
Secondary endpoint:• 30-days mortality• Recurrent PE
Com
posit
e PE
P
0
5
10
15
20
25
Heparin
Alteplase
Heparin TPA
11%
24.6%
Thrombolytic Therapy in patients with non-shock pulmonary embolism?
Am J of Cardiovascular Drugs, 4 (2) 2004 , 69-74
P = 0.0058
In-h
ospi
tal
Mor
talit
y
5
4
3
2
1
0
2.4%
2.1%
P = NS
Non-shock PE: Pathobiology
Observations: • Clinical observation• Lack of response to anti-obstructive lytic
treatment
Science: • Inflammatory neurohormonal mediators’
release bilateral pulmonary vasoconstriction, bilateral V/Q mismatch PVR RV dysfunction
Stein M, Prog Cardiovasc Dis 1974; 17:167-174Malik AB, Physiol Rev 1983; 63: 1114-1207 Alpert JS, Chest 1978; 73: 795-797
Methods:
• Inhaled Iloprost used in 11 patients with Submassive PE, who refused to receive thrombolytic therapy
• NYHA III to IV for duration between 1-14 day• Helical CT angiogram was confirmatory• Echocardiography was used to evaluate the RV
•All patients were stable hemodynamically
• Beside anticoagulation, all patients received inhaled Iloprost, 2.5-5 µg every 4 hours for 3 weeks.
Novel approach for the management of sub-massive pulmonary embolism
Idrees et al. Ann Thorac Med 2012; 7(3):157-161.
SMC fibroblasts monoc T-cellsPMN
vasodilation
Prostanoids
matrixsecretion
TNFIFNIL-2
burstelastaseleuko-trienes
NFkBTNFIL-1IL-10
anti-coagulation
platelets
anti-proliferation
MAPKiNOS
Vessels LeukocytesPlatelets
Olschewski et al. Pharmacol Ther, 2004
Novel approach for the management of sub-massive pulmonary embolism
End points: • Improvement in echocardiographic parameters
for right ventricular strain/PH
• Functional class improvement• Improvement in dyspnea score• Exercise improvement• Biomarker (Pro BNP)• Improvement in oxygenation• Mortality
Idrees et al, ATM, Submitted
Results
Pre IloprostPost Iloprost
sPAP NT - Pro 6MWT Dyspnea NYHA BNP Score
Idrees et al, ATM, Submitted
P < 0.003
lll +
l +
Vlll
ll
P = 0.03
155 m
520 m
P = 0.01
1620
420
P < 0.001P = 0.01
38
89
100
80
60
40
20
1800
1500
1200
900
600
300
0
600 -- 450 --
300 --
150 --0
X
VIII
VI
IV
II
0
IV
III
II
I
0
Novel approach for the management of sub-massive pulmonary embolism
Idrees et al, ATM, Submitted
Conclusion:
• In sub-massive pulmonary embolism, directing therapy towards decreasing PVR is effective in improving the hemodynamics derangement associated with this condition.
• This strategy might turn to be the most effective approach for treating this condition and probably safer than thrombolytic therapy.
• However, these conclusion should be confirmed in a large, randomized, placebo-controlled study
Take Home Messages
The 55th ESCT conference
Summary
•Pulmonary embolism could be a fatal disease•Diagnostic-Therapeutic approach based on risk
stratification is probably the most important step in the management
o RV Dysfunctiono Shock
o Cardiac arresto Sudden arrest
Summary
Thrombolytic therapy in M-PE:
• Accelerated clot lysis• Hemodynamic improvement• May improve
Recurrent embolism CTEPHQuality of life Symptoms Mortality
Thrombolytic therapy in SM-PE:• Controversial issue• Administrating early in the course of sub-
massive pulmonary embolism prevents worsening of the disease
In SM-PE• Directing therapy towards PVR rather than clotting lysis might be
the ideal approach in this patients’ population• Need to be tested in randomized clinical studies
Thank you
Egyptian Society of Chest Diseases & Tuberculosis The 55th International Conference
25-28 March 2014Cairo, Egypt