Epidemiology. Update on Pulmonary Embolism. Keys to PE Management 5/5/2014. Diagnosis. Risk stratification. Treatment

Transcription

1 Update on Pulmonary Embolism Steven M. Dean, DO, FACP, RPVI Program Director- Vascular Medicine Associate Professor of Internal Medicine Division of Cardiovascular Medicine The Ohio State University Keys to PE Management Diagnosis Risk stratification Treatment Epidemiology ,000 cases diagnosed annually 2. PE is the 3 rd most common cardiovascular disease after myocardial infarction and stroke. 3. The death rate from PE exceeds the death rate from myocardial infarction because MI is much easier to detect and to treat 4. 20% die suddenly from PE 5. PE responsible for up to 150,000 deaths/year 1

2 Venous Thromboembolism Location of DVT Incidence of PE % Proximal 45% Distal 44% Tibial 43% Popliteal 47% Femoral 49% Iliac 38% Caval 42% European multicentered, randomized, doubleblind trial of proximal DVT treatment performed baseline V/Q scans DVT is PE in transit % Monreal et al. Chest 1992;102: Meigan et al. Arch Intern Med 2000;160: Frequency of PE in DVT 8-15% symptomatic at presentation New PE after treatment in 3-8% of patients Partsch et al. JVS 1996;24: Borst-Krafek et al. JVS 2003;37: Partsch et al. JVS 1992;16: Pacouret et al. Arch Intern Med 1997;157 Diagnosis 2

3 If there is no contraindication treat while you figure it out Clinical diagnosis of PE is UNRELIABLE! The Pretest probability of disease must be assessed 0bjective imaging is mandatorydicti tools assist with initial assessment Diagnosis of PE Clinical signs and symptoms are nonspecific and lack adequate positive or negative predictive value for diagnosis Stawicki et al. J Clin US 2008;36:

4 The Pretest probability of disease must be assessed <4 Unlikely >4 Likely Christopher Study Investigators. JAMA 2006;295(2):

5 0.5% Pollak. Mayo Clin Proc 2014;89(3): D-Dimer Degradation of terminally cross-linked fibrin Should be used mainly in the outpatient or ED setting in low clinical probability cases to determine the need for further testing Not helpful in malignancy, trauma, post-op, or acute illness/inflammation, sepsis, advanced age Clinical cut-off (<500 mg/dl) depends on the assay high negative predictive value (95-98%) D-Dimer Negative result is helpful to EXCLUDE PE Positive result not helpful Positive D-dimer does NOT rule-in PE Negative D-dimer with a low clinical risk assessment essentially excludes the need for further testing 5

6 Diagnosis of PE High Pre-test Prob & Negative Scan 3 month cumulative PE 1.5% CT pulmonary angiography is the most common imaging modality used to diagnose PE with a high sensitivity & specificity. CT angiography Can help assess RV strain risk stratification Subsegmental branch imaging is rapidly improving Now felt to be as good as arteriography May help provide an alternative diagnosis Ventilation/Perfusion Scanning V/Q is not antiquated nor obsolete V/Q has limitations May be limited availability Most useful with a normal CXR and no significant underlying pulmonary disease Useful when contrast sensitivity, renal issues, or access issues prevail Positive or negative tests are useful Significant difficulties with indeterminate scans ( intermediate probability ) Indeterminate is NOT negative! 6

7 Risk Stratification PE Risk Stratification Useful to predict short-term morbidity/mortality Clinical parameters Cardiac echo Biomarkers RV/LV ratio?useful to direct therapeutic choices 7

8 Massive vs. Submassive PE Massive PE SBP<90mmHg for 15 min Inotropic support Pulselessness Persistent bradycardia (HR < 40 bpm) Circulation 2011;123:1788 Submassive PE SBP 90mmHg RV dysfunction RV dilatation ECHO or CT (RV/LV diameter > 0.9) BNP > 90 pg/ml EKG changes Myocardial necrosis: Troponin I > 0.4 ng/ml Troponin T > 0.1 ng/ml Risk Stratification Piazza et al. Circulation 2006;114:e42-e47. Chest 2008; 133 (suppl) 454S-545S 8

9 Biomarker Risk Stratification Kucher et al. Circulation 2003;108: Biomarkers in PE Becattini meta-analysis Circ troponin elevation in submassive PE: OR = 5.9 Sanchez meta-analysis Eur Heart Jn OR for short term mortality for BNP and N-terminal pro-bnp in submassive PE 9.5 and 5.7, respectively Echocardiography POOR PROGNOSITIC INDICATORS RV dilation and hypokinesis Paradoxical interventricular septal motion RV thrombus Tricuspid regurgitation Pulmonary hypertension McConnell s sign most specific ECHO finding Severe RV free wall hypokinesis with sparing of the apex 9

10 ECHO Risk Stratification 1035 pts from ICOPER registry SBP > 90 mmhg 30-day survival 83.7% with RV hypokinesis 90.6% without RV hypokinesis Kucher et al. Arch Intern Med 2005;165: CT Risk stratification Multiplanar reformatting, 4-chamber reconstructed images RV D /LV D > 0.90 HR 3.4 Schoepf et al. Circulation 2004;110:

11 Treatment Goals of PE Therapy Restore cardiopulmonary hemodynamics Avoid chronic thromboembolic pulmonary hypertension Reduce recurrence Prevent death Initial Anticoagulation of Pulmonary Emboli o Acute, nonmassive PE: LMWH is preferred over IV UFH [Grade IA] o Massive PE/thrombolysis candidate: IV UFH [Grade 2C] preferred over other anticoagulants 11

12 The Facts Approximately 20% of patients with PE die before diagnosis or on the first day after diagnosis. For those surviving more than one day, up to 11% may die in the first three months, even with adequate therapy. Heit JA et al. Arch Int Med. 1999;159(5): PE Mortality (ICOPER) 52.4%* 14.7% *62.5% from recurrent PE Kucher et al Massive PE Circulation All comers - Lytic and no Lytic Submassive PE Is there a role for systemic thrombolysis for sub-massive PE? Should sub-massive PE be treated more aggressively? 12

13 What is the Dose of IV tpa? Guidelines Recommend: IV tpa 100 mg over a 2 hour continuous infusion.. A Major Disadvantage of Systemic Dosed IV tpa is: BLEEDING Thrombolysis Bleeding Risk: Controlled Trials Adapted from Konstantinides 13

14 Thrombolysis Bleeding Risk: Registries/RetrospectiveTrials (3%) 142/669 (21.2%) 16/669 (2.4%) Adapted from Konstantinides Pharmacology 101 The Larger the Dose The Higher the Risk AHA Scientific Statement March 2011 Meta-Analysis of 13 randomized trials of thrombolysis vs anticoagulation alone. No significant reduction in recurrent PE or death with thrombolytic therapy. Alteplase treatment was associated with a significantly higher rate of hemorrhage than anticoagulation alone. Neither recurrent PE nor death was significantly different in the alteplase versus placebo groups. 14

15 Thrombolytic Therapy for Pulmonary Embolism Meta-analysis of 8 randomized trials (679 pts); stable pts with acute PE who received thrombolysis followed by heparin were compared to those who received heparin alone. No statistically significant differences between Rx groups in terms of: Mortality: OR 0.89; 95% CI Recurrent PE: OR 0.63; 95% CI Dong et al. Cochrane Database Syst Rev 2006; CD PEITHO Trial ACC 2013 Randomized double blind 1006 patients Evaluated efficacy and safety of single IV bolus TNK vs anticoagulation in normotensive PE patients Primary endpoint: Death from any cause Circulatory collapse Konstantinides March 2013 ACC PEITHO Trial ACC 2013 Results: It s a wash The benefits of TNK equals risks from bleeding Primary endpoint decreased by 56% with TNK Major bleeding significant with TNK (6.3 vs 1.5 %) 10 hemorrhagic strokes with TNK 1 hemorrhagic stroke with anticoagulation alone Konstantinides March 2013 ACC 15

16 Systemic Thrombolysis Real World Systemic thrombolysis has absolute and relative contraindications. Up to 2/3 of patients with PE do not receive therapy due to contraindications. In patients without contraindications, up to 20% major hemorrhagic complications and 3 5% of intracranial bleeds have been reported. Goldhaber ICOPER 1999 Fiumara Am J Card 2006 So Why Interventional Therapy for PE? Total dose of thrombolytic agent much less Catheter directed therapy much more efficient More rapidly restores systemic perfusion Access to IVC allows placement of IVC filters to prevent recurrent PE EKOS Technology Microsonic energy breaks the fibrin strands making the thrombus more permeable to the thrombolytic drug 16

17 Prospective evaluation of right ventricular function and functional status 6 months after acute submassive pulmonary embolism 200 patients with submassive PE All treated with anticoagulation 21/200 received thrombolysis due to worsening clinical status Baseline RVSP measured in all patients 6 month F/U of RVSP, NYHA class, and 6 min walk test Kline et al. Chest Nov;136(5): Prospective evaluation of right ventricular function and functional status 6 months after acute submassive pulmonary embolism RVSP was higher than baseline in 27% who received anticoagulation alone at 6 months. 46% of these pts had a NYHA class > 3 and poor 6 minute walking distance at 6 months. The RVSP at follow-up was not higher than at the time of diagnosis in any of the thrombolytic patients. Six months after experiencing submassive PE, a significant proportion of patients had echocardiographic and functional evidence of pulmonary hypertension Kline et al. Chest Nov;136(5): Should We be More Aggressive in Patients with Sub-Massive PE? 209 consecutive patients with PE Shock or cardiac arrest: 13% Hypotension without shock: 9% Normotensive without RVD 47% Normotensive with RVD 31% 10% who were normotensive with RVD deteriorated, and 50% died. Grifoni S. Circulation 2000:101;

18 So Why Interventional Therapy for PE? Total dose of thrombolytic agent much less Catheter directed therapy much more efficient Thrombectomy (when needed) more rapidly unloads RV and restores perfusion to lungs More rapidly restores systemic perfusion Access to IVC allows placement of IVC filters to prevent recurrent PE Thank You 18