Pulmonary Heart-Pulmonary Embolism PDF

ΠΜΣ «Επεμβατική Καρδιολογία» Πνευμονική καρδία-Πνευμονική εμβολή Ηρακλής Τσαγκάρης Καθηγητής Πνευμονολογίας Εντατικής Θεραπείας Αττικό Νοσοκομείο Pulmonary Circulation Pulmonary Circulation Pressures Distribution of blood circulation 1. 280 billion c...

ΠΜΣ «Επεμβατική Καρδιολογία» Πνευμονική καρδία-Πνευμονική εμβολή Ηρακλής Τσαγκάρης Καθηγητής Πνευμονολογίας Εντατικής Θεραπείας Αττικό Νοσοκομείο Pulmonary Circulation Pulmonary Circulation Pressures Distribution of blood circulation 1. 280 billion capillaries, supplying 300 million alveoli 2. Total volume of blood in all vessels 1. man: 5.4 l (70-80 ml / kg) 2. woman: 4.5 l (65-70 ml / kg) 3. Distribution: 1. Heart 7% 2. Pulmonary circulation 9-10% 3. Systemic circulation 84% 1. from that veins 75% 2. large arteries 15% 3. small arteries 3% 4. capilaries: 7% Two Circulations in the Lung Pulmonary Circulation. Arises from Right Ventricle. Receives 100% of blood flow. Bronchial Circulation. Arises from the aorta. Part of systemic circulation. Receives about 2% of left ventricular output. Pulmonary circulation Pulmonary artery wall 1/3 as thick as aorta RV 1/3 as thick as LV All pulmonary arteries have larger lumen more compliant operate under a lower pressure can accommodate 2/3 of SV from RV Pulmonary veins shorter but similar compliance compared to systemic veins Total Pulmonic Blood Volume 450 ml (9% of total blood volume) reservoir function 1/2 to 2X TPBV shifts in volume can occur from pulmonic to systemic or visa versa e.g. mitral stenosis can  pulmonary volume 100% shifts have a greater effect on pulmonary circulation Systemic Bronchial Arteries Branches off the thoracic aorta which supplies oxygenated blood to the supporting tissue and airways of the lung. (1-2% CO) Venous drainage is into azygous (1/2) or pulmonary veins (1/2) (short circuit) drainage into pulmonary veins causes LV output to be slightly higher (1%) than RV output & also dumps some deoxygenated blood into oxygenated pulmonary venous blood Pulmonary lymphatics Extensive & extends from all the supportive tissue of lungs & courses to the hilum & mainly into the right lymphatic duct remove plasma filtrate, particulate matter absorbed from alveoli, and escaped protein from the vascular system helps to maintain negative interstitial pressure which pulls alveolar epithelium against capillary endothelium. “respiratory membrane” Pulmonary Circulation In series with the systemic circulation. Receives 100% of cardiac output (3.5L/min/m2). RBC travels through lung in 4-5 seconds. 280 billion capillaries, supplying 300 million alveoli. Surface area for gas exchange = 50 – 100 m2 Alveolar Architecture Alveolar Airspace Alveolar Airspace Functional Anatomy of the Pulmonary Circulation Thin walled vessels at all levels. Pulmonary arteries have far less smooth muscle in the wall than systemic arteries. Consequences of this anatomy- the vessels are: Distensible. Compressible. Pulmonary Circulation Pressures Pulmonary Vascular Resistance input pressure - output pressure Vascular Resistance = blood flow PVR = k mean PA pressure - left atrial pressure cardiac output (index) mean PA pressure - left atrial pressure = 10 mmHg mean aorta pressure - right atrial pressure = 98 mmHg Therefore PVR is 1/10 of SVR Vascular Resistance is Evenly Distributed in the Pulmonary Circulation Reasons Why Pressures Are Different in Pulmonary and Systemic Circulations? Gravity and Distance: Distance above or below the heart adds to, or subtracts from, both arterial and venous pressure Distance between Apex and Base Systemic Pulmonary Aorta 100 mmHg Main PA 15 mmHg Head 50 mmHg Apex 2 mmHg Feet 180 mmHg Base 25 mmHg  Reasons Why Pressures Are Different in Pulmonary and Systemic Circulations? Control of regional perfusion in the systemic circulation: Large pressure head allows alterations in local vascular resistance to redirect blood flow to areas of increased demand (e.g. to muscles during exercise). Pulmonary circulation is all performing the same job, no need to redirect flow (exception occurs during hypoxemia). Consequences of pressure differences: Left ventricle work load is much greater than right ventricle Differences in wall thickness indicates differences in work load. Influences on Pulmonary Vascular Resistance Pulmonary vessels have: -Little vascular smooth muscle. -Low intravascular pressure. -High distensiblility and compressiblility. Vessel diameter influenced by extravascular forces: -Gravity -Body position -Lung volume -Alveolar pressures/intrapleural pressures -Intravascular pressures Influences of Pulmonary Vascular Resistance Transmural pressure = Pressure Inside – Pressure Outside. –Increased transmural pressure-increases vessel diameter. –Decreased transmural pressure-decreased vessel diameter (increase in PVR). –Negative transmural pressure-vessel collapse. Pi Poutside Different effects of lung volume on alveolar and extraalveolar vessels. Effect of Transmural Pressure on Pulmonary Vessels During Inspiration Resistance  Length and Resistance  1/(Radius)4 Effect of Lung Volume on PVR  5th World Symposium on PH: Haemodynamic definition of PAH Mean PAP ≥ 25 mmHg Definition Mean PAP Definition of PAWP of PH ≥ 25 mmHg PAH ≤ 15 mmHg PVR > 3 Wood units PAP: pulmonary arterial pressure; PAWP: pulmonary artery wedge pressure; PVR: pulmonary vascular resistance Hoeper MM, et al. J Am Coll Cardiol 2013; 62:D42-50.  NEW DEFINITION Mean PAP ≥ 20 mmHg Mean PAP PAWP Definition Definition of of PH ≥ 20 mmHg PAH ≤ 15 mmHg PVR > 3 Wood units PAP: pulmonary arterial pressure; PAWP: pulmonary artery wedge pressure; PVR: pulmonary vascular resistance  NEW DEFINITION Mean PAP ≥ 20 mmHg Mean PAP PAWP Definition Definition of of PH ≥ 20 mmHg PAH ≤ 15 mmHg PVR > 2 Wood units PAP: pulmonary arterial pressure; PAWP: pulmonary artery wedge pressure; PVR: pulmonary vascular resistance Αpical 4-chamber Normal PAH Parasternal short axis Normal PAH Tricuspid Regurgitation  PULMONARY EMBOLISM Pulmonary embolus (PE) refers to obstruction of the pulmonary artery or one of its branches by material (eg, thrombus, tumor, air, or fat), originated elsewhere in the body.  ✓ Acute pulmonary embolism (PE) is a form of venous thromboembolism (VTE) that is common and sometimes fatal. (> 50% of pts with proximal DVT have concurrent PE at presentation)1 ✓ 70% of pts with PE have DVT.2 ✓ Most emboli arise from lower extremity proximal veins (iliac, femoral, and popliteal), but may also originate in right heart, inferior vena cava, the pelvic, the renal and upper extremity veins. 1.Moser KM, et al. Frequent asymptomatic PE in pts with deep venous thrombosis. JAMA 1994;271: 223–225. 2.Kearon C. Natural history of venous thromboembolism. Circulation 2003;107(23 Suppl. 1):I22–I30.  Classification (1) Acute : Patients with acute PE typically develop symptoms and signs immediately after obstruction of pulmonary vessels. Subacute : Some patients with PE may also present subacutely within days or weeks following the initial event. Chronic : Patients with chronic PE slowly develop symptoms of pulmonary hypertension over many years (ie, chronic thromboembolic pulmonary hypertension; CTEPH).  Classification (2) Hemodynamically unstable PE (shock) : that which results in hypotension. Often (but not always) caused by large (massive) PE. NOT all patients with massive PE develop hypotension. Hemodynamically stable PE : PE that does not meet the definition of hemodynamically unstable PE. Spectrum of severity : from small asymptomatic PE to mild or borderline hypotension that stabilizes in response to fluid therapy, or “intermediate” PE (presents with right ventricle dysfunction).  Classification (3) Saddle PE : lodges at the bifurcation of the main pulmonary artery, often extending into the right and left main pulmonary arteries. (3-6% of PE patients, 22% are hemodynamically unstable) Lobar PE Segmental PE Subsegmental PE Thrombi in the peripheral segmental or subsegmental branches are more likely to cause pulmonary infarction and pleuritis  Classification (4) Symptomatic PE : presence of symptoms that usually leads to the radiologic confirmation of PE Asymptomatic PE : incidental finding of PE on imaging in a patient without symptoms (eg, contrast-enhanced computed tomography)  Pulmonary Embolism ❖ Epidemiology ❖ Risk factors ❖ Diagnosis ❖ Therapy  Pulmonary embolism (PE) ✓PE is a well-recognised and significant cause of morbidity and mortality, estimated to be associated with more than 300 000 deaths per year in Europe alone (Cohen, Thromb Hemost, 2007). ✓Many fatal cases (7%) are not diagnosed pre mortem because of the nonspecific clinical symptoms with which patients often present. ✓A recent german analysis calculated the cost of the first year of PE treatment to be in excess of €20 000 (Kröger, Vasc Med, 2012).  Incidence is increasing ….and cost. Annual cost of 8.5 billion Euros in the European Union  Mortality is decreasing Increased use of more effective therapies and interventions Better adherence to guidelines  Pulmonary Embolism ❖ Epidemiology ❖ Risk factors ❖ Diagnosis ❖ Therapy Interaction between patient-related—usually permanent—risk factors and setting-related—usually temporary—risk factors  Third-generation combined oral contra- ceptives, containing progestogens such as desogestrel or gestodene, are associated with a higher VTE risk than the second-generation combined oral contraceptives, which contain progesto- gens such as levonorgestrel or norgestrl. On the other hand, hormone-releasing intrauterine devices and some progesterone-only pills (used at contra- ceptive doses) are not associated with a significant increase in VTE risk pancreatic cancer haematological malignancies lung cancer gastric cancer and brain cancer  Pulmonary Embolism ❖ Epidemiology ❖ Risk factors ❖ Diagnosis ❖ Therapy 4.11 Recommendations for diagnosis  Clinical presentation : NOT helpful VTE Other diseases ✓Tachypnea : 70% 70 % ✓Tachycardia : 25% 25 % ✓Temperature : 7% 17% (> 38,5) ✓Cyanosis : 10% 10 % 1. Wells P.S: Ann. Int. Med. 1998;129 2. Stein P.D. Chest 1997; 112  Clinical Signs THERE ARE NO SYMPTOMS WITH > 80% SENSITIVITY VTE Other diseases Dyspnea 80% 60% Pleuritic Pain 50% 40% Cough 25% 25% Hemoptysis 10% 10% Shock 22% 10% It is critical that a high level of suspicion be maintained such that clinically relevant cases are not missed Clinical probability assessment (I) % PE patients 10% 30% 65% Clinical probability assessment (II) % PE patients 10% 30% 65% Of the 2946 patients (85%) in whom PE was ruled out at baseline and who were left untreated, 18 [0.61%, 95% confidence interval (CI) 0.360.96%] were diagnosed with symptomatic VTE during the 3 month follow-up. CTPA was avoided in 48% of the included patients using this algorithm, compared to 34% if the Wells rule and a fixed D-dimer threshold of 500 ng/mL would have been applied  Diagnostic Imaging ✓Chest X-ray ✓Ventilation-perfusion scintigraphy (V/Q scan) ✓Multiple detector computed tomography (MDCT) ✓Conventional angiography ✓MRI ✓Compression venous ultrasonography No means no?  Chest X-ray ✓ Positive, in the majority of cases. (88% in PIOPED study). ✓ Nonspecific findings (cardiomegaly, pleural effusion, elevated hemidiaphragm, pulmonary artery dilatation, parenchymal infiltrates, etc.). ✓ Specific findings, rare (Hampton’s hump, Westermark’s sign).  Ventilation-Perfusion Scan V/Q Scan ✓Ventilation / perfusion mismatch ✓Normal V/Q Scan excludes PE (NPV> 95%) ✓High probability V/Q Scan → Relatively high PPV (85-90%) ✓High prevalence of non – diagnostic tests (40-70%). RIM SIGN RAILROAD TRACK SIGN RIDING OR SADDLE EMBOLUS VESSEL “CUT-OFF” SIGN  Acute PE Infractions ✓ Peripheral , triangular, broad pleural-based lession ✓ No radiocontrast uptake ✓ No airbronchogram ✓Vascular sign RV Dysfunction  CT in PE Mild RV dilation (RV/LV slightly above 0.9) on CT is a frequent finding (>50% of haemodynamically stable PE patients)* A meta-analysis of >13 000 patients with PE confirmed that an increased RV/LV ratio of >_1.0 on CT was associated with a 2.5- fold increased risk for all-cause mortality, and with a five-fold risk for PE-related mortality** *Cote´ B, Jimenez D, Planquette B, Roche A, et L. Prognostic value of right ventricular dilatation in patients with low-risk pulmonary embolism. Eur Respir J 2017;50:1701611. **Meinel FG, Nance JW Jr, Schoepf UJ, et al. Predictive value of computed tomography in acute pulmonary embolism: systematic review and meta-analysis. Am J Med 2015;128:747759.e2. Findings of pre-existing chronic thromboembolic pulmonary hypertension on computed tomography pulmonary angiography SPECT CT Main new recommendations 2019 RV Dysfunction  Pulmonary Embolism ❖ Epidemiology ❖ Risk factors ❖ Diagnosis ❖ Therapy The myth A missed PE a dead patient PESI (Pulmonary embolism severity index) Case 1: Risk?? PESI 1/ sPESI 0  - Until the clinical implications of such discrepancies are clarified, patients with signs of RV dysfunction or elevated cardiac biomarkers, despite a low PESI or an sPESI of 0, should be classified into the intermediate-low-risk Category. Recommendations for prognostic assessment Main new recommendations 2019 Treatment of right ventricular failure in acute high-risk pulmonary embolism Eur Respir J. 2019 Apr Recommendations for acute-phase treatment of high-risk pulmonary embolism Int J Card 2018 Int J Card 2018 Recommendations for multidisciplinary pulmonary embolism teams Yevgeniy Brailovsky et al. J Am Coll Cardiol 2021; 77:1691-1696. D.F.Sosa et al Overview of Pulmonary Embolism Management in the Context of Risk Stratification. SR Kahn, K de Wit. N Engl J Med 2022;387:45-57. Reduced-Dose Intravenous Thrombolysis for Acute Intermediate-High-risk Pulmonary Embolism: Rationale and Design of the Pulmonary Embolism International THrOmbolysis (PEITHO)-3 trial O.Sanchez, S.Konstantinides et al PEITHO-3 Investigators Patients with intermediate-high-risk PE will also fulfill at least one clinical criterion of severity: systolic blood pressure ≤110 mm Hg, respiratory rate >20 breaths/min, or history of heart failure The primary efficacy outcome is the composite of all-cause death, hemodynamic decompensation, or PE recurrence within 30 days of randomization. Further outcomes include PE-related death, hemodynamic decompensation, or stroke within 30 days; dyspnea, functional limitation, or RV dysfunction at 6 months and 2 yrs The study is planned to enroll 650 pts Thromb Haemost 2022; 122(05): 857-866 Methods: 1. Confirmed acute PE 2. Evidence of RV dysfunction on imaging 3. Positive cardiac troponin test 4. Clinical criteria indicating an elevated risk of early death or imminent hemodynamic collapse Pharmaco-mechanical reperfusion strategies Sista AK et al JACC Cardiovascular interventions 2021;14(3):319-329 Recommendations for acute-phase treatment of intermediate- or low-risk pulmonary embolism Recommendations for acute-phase treatment of intermediate- or low-risk pulmonary embolism Recommendations for inferior vena cava filters Case 2 - What is the risk of this patient? 36 year old lady, arrives at the hospital alone, on foot Presents with a swollen leg, mild retrosternal discomfort. Patient’s family doctor just diagnosed DVT by CUS and sent her to the hospital. At the hospital: BP: 130/80 mm Hg; HR: 80/min, regular SO2: 98% under room air Heart and lungs normal Patient wants to go home right away, she “feels good”! What to do now? Patient with confirmed DVT and dyspnoea: a) CTPA is now necessary to diagnose PE. b) No further tests necessary, this patient has DVT, and thus VTE, and is stable; start rivaroxaban and let her go home right away! c) I will keep her in the hospital and on the monitor for 2 days to make sure she will not decompensate d) I need more information to decide  Home treatment: Check risk, feasibility AND RV status! NO haemodynamic instability ✓ NO need for oxygen ✓ NO need for parenteral analgesia ✓ NO extreme obesity ✓ NO serious comorbidity ✓ Patient compliance with treatment ✓ Support from family/social environ. ✓ NO RV dysfunction on CT or echo! Recommendations for early discharge and home treatment Case 3 :A patient presenting 6 months after PE 63 year-old lady, 163 cm, 60 kg ❖ She was healthy until December 2018 ❖ She suffered acute PE after flying from Athens to London (a little less than 4 hours) ❖ Was given rivaroxaban 20 mg once daily; treatment well tolerated ❖ Came to our PE outpatient service last week: She would like to stop the anticoagulant, but she is also afraid of a new PE episode What is your advice? a) Yes, she can stop now, this was provoked PE (economy class syndrome!) b) No, she should continue treatment lifelong, this prevents life-threatening PE recurrence! c) I would continue, but the dose can be reduced now to 10 mg once daily d) I do not know, let the patient decide  Most pts candidates for extended anticoagulation i) patients in whom a strong (major) transient or reversible risk factor, most commonly major surgery or trauma, can be identified as being responsible for the acute (index) episode; (ii) patients in whom the index episode might be partly explained by the presence of a weak (minor) transient or reversible risk factor, or if a non-malignant risk factor for thrombosis persists; (iii) patients in whom the index episode occurred in the absence of any identifiable risk factor (the present Guidelines avoid terms such as ‘unprovoked’ or ‘idiopathic’ VTE); (iv) patients with one or more previous episodes of VTE, and those with a major persistent pro-thrombotic condition such as antiphospholipid antibody syndrome; (v) patients with active cancer  Indefinite anticoagulant treatment Patients who are carriers of some forms of hereditary thrombophilia, notably those with confirmed deficiency of antithrombin, protein C, protein S, homozygous factor V Leiden homozygous prothrombin G20210A mutation, are often candidates for indefinite anticoagulant treatment after a first episode of PE occurring in the absence of a major reversible risk factor.  Thrombophilia testing Testing for thrombophilia (including antiphospholipid antibodies and lupus anticoagulant) may be considered in patients in whom VTE occurs at a young age (e.g. aged 3 mmHg/L/min) during exercise or dead space ventilation Eur Heart J, Volume 43, Issue 3, 14 January 2022, Pages 183–189  The most relevant potentially Incomplete thrombus resolution modifiable risk factors for occurs in 25–50% of patients bleeding: renal insufficiency,liver after acute PE despite adequate disease,thrombocytopenia, anaemia, anticoagulation, but bears no hypertension, antiplatelet or NSAI clinical significance in most drugs cases. After the first 3–6 months, Follow-up studies have shown estimation of the risk of bleeding that 40% of PE survivors have becomes relevant for patients at persistent perfusion defects - high risk of recurrent venous only a very small proportion are thromboembolism (VTE), for whom ultimately diagnosed with CTEPH indefinite treatment is considered Eur Heart J, Volume 43, Issue 3, 14 January 2022, Pages 183–189 Eur Heart J, Volume 43, Issue 3, 14 January 2022, Pages 183–189  Τι άλλαξε ουσιαστικά? Ρόλος της δεξιάς κοιλίας ↑↑ Διακλινική ομάδα αντιμετώπισης Θρομβόλυση/εμβολεκτομή-ECMO NOACs Κύηση Διάρκεια θεραπείας - Χρόνιες επιπλοκές Jimenez D, Am J Respir Crit Care Med. 2023 M.E. Farkouh et al. J Am Coll Cardiol 2022; 79:917-928.  (A) Clinical outcomes in the strata of noncritically ill hospitalized patients Left. Survival until hospital discharge without receiving organ support. Right. Major bleeding tended to be Survival Major increased with therapeutic-dose bleeding anticoagulation (B) Clinical outcomes in the strata of critically ill hospitalized patients Left.The secondary outcome of survival to hospital discharge (posterior probability of inferiority: 89.2%) Major Survival Right. Major bleeding tended to be bleeding increased with therapeutic-dose anticoagulation. Michael E. Farkouh et al. J Am Coll Cardiol 2022; 79:917-928. 3.600 patients  Summary of the ERS guideline for management of hospitalised patients with COVID-19 N. Roche et al. Eur Respir J doi:10.1183/13993003.00803-2022  The previous version of the guideline made a strong recommendation to use a form of anticoagulation in hospitalized patients with COVID-19, ….but was unable to determine whether prophylactic or treatment dose was superior due to a lack of data No mortality benefit is evident but a reduction in major thrombotic events is balanced by an increase in major bleeding The panel therefore concluded that anticoagulation should continue to be standard care for hospitalized COVID-19 patients … but that the evidence currently does not conclusively favor either prophylactic or therapeutic dose and so both may be appropriate in different patients based on their risk of bleeding versus embolic complications Ευχαριστώ για την προσοχή σας