Vztah reperfuze plicních tepen po akutní plicní embolii k rozvoji chronické tromboembolické plicní hypertenze.

• Thesis title in Czech: Vztah reperfuze plicních tepen po akutní plicní embolii k rozvoji chronické tromboembolické plicní hypertenze.
• Thesis title in English: Relation between the reperfusion of pulmonary arteries after an acute pulmonary embolism to the development of chronic thromboembolic pulmonary hypertension.
• Key words: plicní embolie, reperfuze, chronická tromboembolická plicní hypertenze, hemoglobin
• English key words: Pulmonary embolism, reperfusion, chronic thromboembolic pulmonary hypertension, hemoglobin
• Academic year of topic announcement: 2013/2014
• Thesis type: dissertation
• Thesis language: čeština
• Department: 2nd Department of Medicine – Department of Cardiovascular Medicine First Faculty of Medicine Charles University and General University Hospital in Prague (11-00520)
• Supervisor: prof. MUDr. Pavel Jansa, Ph.D.
• Author: hidden - assigned and confirmed by the Study Dept.
• Date of registration: 13.08.2014
• Date of assignment: 13.08.2014
• Confirmed by Study dept. on: 13.08.2014
• Date and time of defence: 12.09.2019 10:00
• Venue of defence: Fyziologický ústav 1. LF UK, Albertov 5, 128 00 Praha 2
• Date of electronic submission: 13.05.2019
• Date of proceeded defence: 12.09.2019
• Course: Defence of the dissertation (B90002)
• Opponents: doc. MUDr. Hana Maxová, Ph.D.

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Preliminary scope of work

Porucha reperfuze, respektive porucha rezoluce tromboembolů, je klíčovým faktorem vedoucím od akutní plicní embolie (PE) k chronické tromboembolické plicní hypertenzi (CTEPH). V naší práci jsme hodnotili incidenci, rizikové faktory a klinický dopad poruchy reperfuze po plicní embolii.
Soubor a metodika: Celkem 85 pacientů po první epizodě PE bylo klinicky, scintigraficky a echokardiograficky sledováno 6, 12 a 24 měsíců po příhodě PE.
Výsledky:Perzistující defekty perfuze na perfuzním scintigramu plic byly přítomny po 6 měsících u 23,5 % pacientů, po 12 měsících u 24,9 % pacientů a po 24 měsících u 18,6 % pacientů. Pacienti s perzistujícími defekty při kontrole v 6. měsíci byli obéznější (BMI 30,8 vs 28,3, kg/m2; p 0,012) a měli vyšší hladinu hemoglobinu při iniciální plicní embolii (143,0 vs 136,0 g/l; p 0,012). Pacienti s perzistujícími defekty ve 12. měsíci byli rovněž obéznější (BMI 31,1 vs 28,5kg/m2; p 0,016) a měli vyšší hladinu hemoglobinu při iniciální plicní embolii (144,0 vs 136,0; p 0,007). Pacienti s perzistujícími defekty perfuze ve 24. měsíci po PE byli starší (67,7 vs 55,0; p 0,02), měli vyšší hemoglobin při iniciální PE (144,5 vs 136,0; p 0,031) a jejich iniciální plicní embolie byla častěji středně nebo vysoce riziková (85,7 vs 47,5 %, p 0,026), s čímž souvisel i větší rozměr pravé komory (36,5 vs 32,5 mm; p 0,044) a významnější trikuspidální regurgitace (2,0 vs 1,5; p 0,018) při vstupním echokardiografickém vyšetření. Pacienti s přetrvávajícími defekty perfuze ve 24. měsíci měli také průměrně vyšší hodnotu systolického tlaku v plicnici (30,0 vs 22,5 mmHg) při echokardiografickém vyšetření provedeném ve 24. měsíci, jinak se od skupiny pacientů bez defektů v klinických, funkčních či echokardiografických parametrech nelišili. U tří pacientů (3,5 %) byla přítomna ve 24. měsíci CTEPH.
Ze získaných dat jsme vytvořili predikční skóre, které na základě dvou parametrů – věku a hladiny hemoglobinu – rozdělilo soubor do tří skupin dle rizika přetrvávání perfuzních defektů. Ve skupině nejnižšího rizika (s hladinou hemoglobinu <140 g/l) bylo ve 24 měsíci dosaženo kompletní reperfuze v 94 % případů, ve skupině středního rizika (s hemoglobinem >140 g/l mladších 65 let) bylo dosaženo reperfuze v 75 % případů a ve skupině s nejvyšším rizikem (hemoglobin >140 g/l a věk >65 let) bylo dosaženo reperfuze jen v 66 % případů. Pacienti ve skupině s nejvyšším rizikem měli 9,4 x vyšší riziko přetrvávání perfuzních defektů než pacienti s nejnižším rizikem.
Závěr:Po 24 měsících po akutní PE byla v našem souboru přítomna nekompletní reperfuze u 18,6 % nemocných. Rizikovými faktory nekompletní reperfuze byly vyšší věk, vyšší BMI, vyšší hladina hemoglobinu a středně a více riziková plicní embolie. Pacienti s inkompletní reperfuzí ve 24. měsíci měli vyšší systolický krevní tlak v plicnici. Dle hladiny hemoglobinu a věku při vstupním vyšetření je možno určit u jednotlivých pacientů vysoké, střední a nízké riziko přetrvávání defektů perfuze.

Preliminary scope of work in English

Incomplete resolution of thromboemboli following acute pulmonary embolism (PE) is a key factor in development of chronic thromboembolic pulmonary hypertension (CTEPH). In our study, we evaluated the incidence, risk factors and clinical impact of incomplete reperfusion after acute PE.
Study population and methods: 85 patients after the first acute PE­ were assessed clinically and by pulmonary scintigraphy and echocardiography at month 6, 12 and 24 after an acute PE.
Results: Incomplete reperfusion was detected in 23.5 % of patients after 6 months, in 24.9 % of patients after 12 months and in 18.6 % of patients after 24 months. At month 6, patients with incomplete reperfusion were more obese when compared with patients with normal reperfusion BMI 30.8 vs 28.3 kg/m²; p=0.012) and their initial hemoglobin levels were higher (143.0 vs 136.0 g/l; p=0.012). Similar results were observed at month 12 – patients with residual perfusion defects were more obese (BMI 31.1 vs 28.5; p=0.016) with higher initial hemoglobin levels (144.0 vs 136.0; p=0.007). Patients with incomplete reperfusion at month 24 were significantly older (67.7 vs 55.0 years; p=0.02), their initial hemoglobin levels were higher (144.5 vs 136.0; p= 0.031) and their PE was more frequently of intermediate or high risk (85.7 vs 47.5%; p=0.026). It was associated with larger diameter of the right ventricle (36.5 vs 32.5 mm; p=0.044) and more significant tricuspid regurgitation (2.0 vs 1.5; p= 0.018) during the initial echocardiography examination. The estimated pulmonary arterial systolic pressure was elevated in patients with perfusion defects persisting at month 24 after the acute PE in comparison with remaining patients (30.0 vs 22.5 mmHg). CTEPH was diagnosed in 3 patients (3.5%) from our cohort.
From the acquired data, we created a clinical risk prediction score for persistence of perfusion defects based on two parameters – hemoglobin levels and age. This prediction score classifies our cohort into 3 groups according to the risk of persistence of perfusion defects.
In the lowest risk group (hemoglobin <140 g/l), a complete reperfusion was achieved in 94% after 24 months; in the intermediate risk group (hemoglobin level >140 g/l and age <65 years), reperfusion was achieved in 75%; and in the high risk group (hemoglobin level >140 g/l and age >65 years), reperfusion was achieved only in 66% of cases. The risk of persisting perfusion defects after 24 months was therefore 9.4 times higher in patients in the highest risk group than the in the lowest risk group.
Conclusions: During the 24 months of observation after an acute PE, incomplete reperfusion was detected in 18.6 % of patients. Higher risk of incomplete reperfusion was associated with higher age, higher BMI, higher initial hemoglobin levels and with intermediate or high risk acute PE. It is possible to predict the low, medium or high risk of persisting perfusion defects at each patient according the hemoglobin level and the age at initial examination.