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

The problem

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

Standard of care for PE

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

“Saddle PE” - AngioVac

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

Thrombolytic Therapy Circulation. 2005;112:e28-e32

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) 1997,1165-1171 Kadner et al. J Thorac Cardiovasc Surg. 2008 Aug;136(2):448-51.

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

Results with CDT (“success” without vs with limited lytic) Jaff MR, McMurtry MS, et al. Circulation 2011, 123: 1788-1830 , 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.

Heparin vs Lysis (for Massive PE) Lysis >> Heparin (despite ACCP opposition) Restoration of lung perfusion @ 24 hrs 30-35%  if Rx with lysis Interventional better? Probably, but more data needed. 0.05% if Rx with heparin But, BOTH 65-70% @ 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: 744-749.

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

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;109:2401-2404. Adverse event rate: 54% if RVD/LVD ratio < 0.9 82% if RVD/LVD ratio ≥ 0.9 OR : 4.02 (p=0.041)

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; 166:2151-2156 PE related mortality rate at 3 years: 13.3% if RVD unresolved at discharge 4.4% if RVD resolved at discharge

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; 347:1143-115

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 look @ differences in long term Persistent RV dysfunction Chronic thromboembolic pulmonary hypertension (CTEPH) Impaired Quality of Life

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. 2009 Nov;136(5):1202-10

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, 123:1788-1830

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

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)

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

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 ?

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