Diagnosis and management of Pulmonary embolism.pptx

Diagnosis and management of Pulmonary embolism, recent advances

1. Diagnosis and management of acute pulmonary embolism- Recent advances Gouthami Chennu MD Cardiology grand rounds 12/14/2023

2. Disclosures: none

3. Pulmonary embolism- the burden Global Trends in PE Incidence and Case Fatality Rates JACC 2016;67:976-90 VTE is the third most frequent acute cardiovascular syndrome globally, next to MI and stroke. Causes of over 100,000 deaths annually However, in comparison to ischemic heart disease or stroke, acute PE does not enjoy robust trials and clinical evidence to guide the management.

4. Pulmonary embolism- Diagnosis Most challenging part of management of pulmonary embolism is knowing when to test for PE Common symptoms: fatigue, breathlessness, chest pain, dizziness, cough, diaphoresis, fever, and hemoptysis. I nitial misdiagnosis is common.

5. Kahn et al, July 2022, NEJM

6. Diagnosis

7. Risk stratification

8. Risk stratification Definition of hemodynamic instability, which delineates acute high-risk pulmonary embolism (one of the following clinical manifestations at presentation)

9. Case: 1 48 years old male presented with acute onset shortness of breath after a 10.5 hour long flight. Associated symptoms: orthostatic symptoms, chest tightness, nausea, diaphoresis. PMH: Hypertension Vitals at the time of presentation: Temperature 97.6- 98F; BP 133-110/68-84; heart rate: 102-111bpm; RR- 20-24/min. SpO2: 91% on 4l O2 supplementation Troponin: 0.32 (normal: <0.03) sPESI score: 2 CTA PE study: “Saddle pulmonary embolism at the bifurcation of the main pulmonary arteries with extension into right and left lobar and segmental branches. There is moderate right heart strain”

10. Case: 2 47 years old female who presented with sudden onset, worsening shortness of breath for 1 day. Associated symptoms: chest tightness, lightheadedness PMH: HTN, hypothyroidism, tobacco use Vitals at the time of presentation: Temperature: 97.9 F; BP135-187/81-115 heart rate: 105-115, RR-25-33 /min. SpO2: 96% without any O2 supplementation. sPESI score: 1 Troponin: 1970 (normal: <53.7) CTA PE study: “Acute bilateral pulmonary emboli scattered diffusely throughout the proximal segmental pulmonary arteries bilaterally with associated right heart strain..”

11. Case: 3 67 years old female who presented with sudden onset shortness of breath after a 19 hr long flight. Associated symptoms: chest tightness, lightheadedness PMH: HTN, HLD Vitals at the time of presentation: Temperature: 98.1F; BP134-143/76-83, heart rate: 75-85, RR-16-20 /min. SpO2: 96% without any O2 supplementation. sPESI score: 0 Troponin: 573 (normal: <53.7) CTA PE study: “Bilateral acute pulmonary emboli involving lobar, segmental and subsegmental branches. Evidence of right heart strain.”

12. Case: 1 48 years old male presented with acute onset shortness of breath after a 10.5 hour long flight. Associated symptoms: orthostatic symptoms, chest tightness, nausea, diaphoresis. PMH: Hypertension Vitals at the time of presentation: Temperature 97.6- 98F; Bp 133-110/68-84; heart rate: 102-111bpm; RR- 20-24/min. SpO2: 91% on 4l O2 supplementation Troponin: 0.32 (normal: <0.03) sPESI score: 2 CTA PE study: “Saddle pulmonary embolism at the bifurcation of the main pulmonary arteries with extension into right and left lobar and segmental branches. There is moderate right heart strain” Clinical course: Underwent Catheter directed thrombolysis on the day of presentation; Went in to PEA cardiac arrest and pronounced dead the day after presentation.

13. Key factors contributing to hemodynamic collapse and death in acute pulmonary embolism

14. Case: 2 47 years old female who presented with sudden onset, worsening shortness of breath for 1 day. Associated symptoms: chest tightness, lightheadedness PMH: HTN, hypothyroidism, tobacco use Vitals at the time of presentation: Temperature: 97.9 F; BP135-187/81-115 heart rate: 105-115, RR-25-33 /min. SpO2: 96% without any O2 supplementation. sPESI score: 1 Troponin: 1970 (normal: <53.7) CTA PE study: “Acute bilateral pulmonary emboli scattered diffusely throughout the proximal segmental pulmonary arteries bilaterally with associated right heart strain..” Clinical course: Was randomized to heparin only group Hi-PEITHO trial. Remained stable hemodynamically. Was discharged home on Apixaban.

15. Case: 3 67 years old female who presented with sudden onset shortness of breath after a 19 hr long flight. Associated symptoms: chest tightness, lightheadedness PMH: HTN, HLD Vitals at the time of presentation: Temperature: 98.1F; BP134-143/76-83, heart rate: 75-85, RR-16-20 /min. SpO2: 96% without any O2 supplementation. sPESI score: 0 Troponin: 573 (normal: <53.7) CTA PE study: “Bilateral acute pulmonary emboli involving lobar, segmental and subsegmental branches. Evidence of right heart strain.” Clinical course: admitted to floors, treated with IV heparin. Discharged home on Apixaban

16. Pathophysiology Acute PE interferes with both circulation and gas exchange.  Hypoxemia: ventilation/perfusion mismatch . Low cardiac output, with resulting low mixed venous oxygen saturation. Increased anatomic or physiologic dead space In about one-third of patients, right-to-left shunting through a patent foramen ovale can be detected by echocardiography- severe hypoxemia, paradoxical emboli Pulmonary infarction- hemoptysis, pleuritis, pleural effusion.

17. PE severity is a continuum and the risk of dying of PE varies within, as well as between, risk categories. It is estimated that 1 in 20 patients with intermediate-high risk acute PE can decompensate hemodynamically during the hospital stay.

18. Future directions in risk stratification of acute PE Giri et al, Circulation 2019 Nov 12

19. NEWS

20. Inclusion criteria Age 18 years or older; acute pulmonary embolism (first symptoms occurring 15 days or less before randomization) confirmed by lung scan, or a positive spiral computed tomogram, or a positive pulmonary angiogram; right ventricular dysfunction confirmed by echocardiography or spiral computed tomography of the chest, myocardial injury confirmed by a positive troponin I or T test.

21. Chatterjee et al., JAMA. 2014 Jun 18

22. Systemic thrombolysis The risks and benefits of systemic thrombolysis are closely counter balanced in the intermediate-risk PE population. The optimal dose and duration of systemic thrombolysis are unknown. PEITHO 3 trial: R andomized, placebo-controlled, double blind, multicenter, multinational trial with long-term follow-up. Designed to assess the efficacy and safety of a reduced dose of thrombolytic therapy given in addition to LMW heparin in patients with intermediate-high-risk acute PE Alteplase or placebo given within 30 minutes of randomization as a 15 min intravenous infusion at a dosage of 0.6 mg/kg with a total dose not exceeding 50 mg.

23. Device therapies A ttempt to rapidly decrease thrombus burden via pharmaco-mechanical means. 2 categories: catheter-directed thrombolysis (CDT) catheter-based embolectomy. Current use of these therapies is predicated on thrombus burden, hemodynamics, overall patient condition, bleeding risk, and operator/institutional preferences and experience.

24. Catheter directed thrombolysis Administration of pharmacological thrombolysis via catheter directed injection of a thrombolytic drug directly into the PA circulation Goal is to achieve similar or improved effectiveness compared with systemic thrombolysis while decreasing the rate of major bleeding.

25. Catheter based embolectomy The Flow- Triever system (Inari Medical, Irvine, CA) is a large-bore device that mechanically engages thrombus through deployment of 3 self-expanding nitinol disks. The disks are retracted back into the catheter with entrapped thrombus while the large-bore guiding catheter is aspirated.

26. Catheter based embolectomy The Flow- Triever system (Inari Medical, Irvine, CA) is a large-bore device that mechanically engages thrombus through deployment of 3 self-expanding nitinol disks. The disks are retracted back into the catheter with entrapped thrombus while the large-bore guiding catheter is aspirated.

27. Catheter based embolectomy The Indigo Thrombectomy System (Penumbra, Inc, Alameda, CA) S maller bore aspiration catheter designed to engage thrombus and extract it with a continuous vacuum pump.

28. Catheter based embolectomy The Indigo Thrombectomy System (Penumbra, Inc, Alameda, CA) is a smaller bore aspiration catheter designed to engage thrombus and extract it with a continuous vacuum pump.

29. Catheter based embolectomy The AngioVac cannula ( AngioDynamics , Inc) is a veno-veno bypass system designed to remove intravascular material via the application of suction. AlphaVac cannula being designed for pulmonary arterial circulation

30. Key trials Trial n Randomized Treatment and comparator Follow-Up, days Intermediate-Risk PE, n (%) Mean Age (Range or SD), y Efficacy ULTIMA, 2013 59 tPA -USAT (20 mg) vs Heparin 90 59 (100) 63.01 (13.51) RV/LV ratio reduced from 1.28±0.19 to 0.99±0.17 at 24 h (P<0.001) SEATTLE II, 2015 150 tPA -USAT (24 mg)  (Single arm) 30 119 (79) 59 (16.1) RV/LV ratio reduced from 1.55 to 1.13 at 48 h (P<0.0001), PASP 51.4 reduced to 36.9 mm Hg (P<0.0001) at 48 h PERFECT, 2015 101 tPA or urokinase, CDT (variable dosing; mean, 28 mg tPA )  (Single arm) 30 73 (72) 60.3 (14.9) PASP 51.17±14.06 to 37.23±15.81 mm Hg (P<0.0001) OPTALYSE PE,  2018 101 tPA -USAT (8–24 mg)  Compared 4 tPA protocols 3 101 (100) 60.0 (29–77) RV/LV ratio reduced in all arms FLARE, 2018 106 FlowTriever  (Single arm) 30 104 (100) 55.6 (13.6) RV/LV ratio 1.53 to 1.15 in 48 h PEITHO, 2014 1006 Tenecteplase, systemic (30–50 mg)  vs Heparin/LMWH/fondaparinux 30 1005 (100) 66.15 (15.29) Death/decompensation at 7 d: 2.6% tenecteplase vs 5.6% placebo (odds ratio, 0.44; 95% CI, 0.23–0.87; P=0.02)

31. P rimary analysis, 2259 patients (N = 1577 USCDT, N = 682 MT) and for the C ontemporary analysis 1798 patients (N = 1137 USCDT, N = 661 MT ) Conclusion: Major bleeding derived from direct laboratory and transfusion data occurred more frequently with MT vs USCDT. Intracranial hemorrhage was more common among MT-treated patients.

32. Ongoing clinical trials in PE Study details Inclusion criteria outcomes Hi-PEITHO Multicenter prospective, randomized trial USCDT vs anticoagulation Acute PE involving at least 1 main or proximal lobar PA 2 out of following 3 HR>100bpm SBP </=110mmHg for 15 minutes or more RR >20/min or SpO2<90% while on RA RV/LV ratio >/+1.0 on CTPA Elevated serum troponin levels PE related death, cardiorespiratory decompensation or collapse or recurrence of PE by Day 7 All cause mortality at 7days, 30 days, 6 months and 1 year STORM PE Multicenter prospective randomized trial AC alone vs AC + Mechanical Aspiration with Indigo Aspiration system Acute PE Intermediate high risk PE: RV/LV >/=1 on CTPA Elevated troponin, BNP and/or NT-pro BNP Change in RV/LV ratio at 48 hours assessed by CTPA MAEs within 7 days, QOL, PE related mortality, all cause mortality at 90 days APEX AV Prospective multicenter single arm study Acute PE RV/LV >/=0.9 SBP : 90mmHg or higher HR </= 130bpm prior to the procedure Primary efficacy and safety endpoints- change from baseline in RV/LV ratio Rate of any major adverse events PE TRACT (NIH) Prospective multicenter RCT CDT+ AC vs AC Intermediate risk PE Proximal thrombus Peak VO2 at 3 months (via cardiopulmonary exercise testing), NYHA class at 12 months PEERLESS Prospective multicenter RCT Large bore MT ( Flowtriever ) vs CDT Acute PE SBP >90mmHg RV dysfunction One of following Elevated troponin h/o heart failure h/o chronic lung disease HR>110bpm SBP<100mmHg RR>/=30/min Spo2<90% Syncope Elevated Lactate At 7 days, All cause mortality Intracranial hemorrhage Major bleeding per ISTH definition Clinical deterioration ICU length of stay

33. Case 4 19 years old female who presented to the ER for evaluation of lower back and bilateral lower extremity pain. PMH: Sickle disease, h/o Pain crisis with multiple hospital admissions, Large ASD with moderate RV dilatation, s/p surgical repair 1 year ago. Was admitted to the GMF for management of pain crisis Vitals: Temp: 37.1; HR 106/114bpm; RR 26/min; BP- 124-134/82-96 mmHg, SpO2 99% on supplemental O2 at 2l/min About 7 hours later, patient was found to be persistently tachycardiac and a CTA chest was ordered for suspicion of acute PE CTA chest : “Linear non occlusive embolus in the main right PA, extending into the main right upper lobe PA and posterior segmental branches of right lobe PA. Straightening of interventricular septum and enlarged right atrium and right ventricle, suggesting right heart strain, uncertain etiology.” Consult was placed to Vascular surgery and Cardiology teams. During evaluation, patient rapidly decompensated and became hemodynamically unstable  PEA cardiac arrest was pronounced dead about 20 hrs after admission.

34. PE response teams The rapidly evolving proliferation of therapeutic options and interventional devices makes choosing among different advanced therapeutic options challenging. Specific therapeutic decisions are left to individual clinicians, who may be prone to their own biases and influenced by their previous experiences. PERT – created to address the treatment and knowledge gaps

35. Studies are needed to explore the impact of PERT involvement in acute PE care on clinical outcomes It is Important to distinguish between impact of PERT involvement and impact of individual therapies

36. Take home points: