Pulmonary Hypertension Transplantation Prof Paul A Corris Newcastle University Newcastle Upon Tyne
Pulmonary Hypertension Which of the following statements are true • A breathless patient with normal LV systolic function and whose RHC results show a mean PAP of 30 mmHg and a PCW of 23 mmHg has pulmonary arterial hypertension • iPAH is associated with thyroid disease • Heritable PAH is associated with mutations in the gene EIF2AK4 • Porto pulmonary hypertension is characterised by severe hypoxia due to intra pulmonary shunting • Thrombocytopaenia is a recognised feature of iPAH
Pulmonary Hypertension A 65 year old female with LcSscl presents with progressive breathlessness. Her thoracic CT shows a dilated RV and PA and no lung fibrosis. RHC(mmHg) shows mean PA 50 , PCW 7, RA 17 CO 2.8 L/min Which of following are true? • She has PAH • She has RHC features supportive of HFpEF • She should receive diuretics • She should receive upfront oral combination therapy with an ERA and a PDE5i • She should be anticoagulated
Pulmonary Hypertension Which of the following statements are true • The V/Q scan is the test with the highest sensitivity for excluding CTEPH • The prognosis of PAH in association with CTD is better than for iPAH • The prognosis of PAH associated with CHD is better than for iPAH • PH associated with sarcoid should be treated with targeted PH therapy as in patients with iPAH • Studies have shown an increase in mortality if patients with IPF and PH are treated with endothelin receptor antagonists
Pulmonary Hypertension Which of the following are true statements regarding CTEPH • Increased risk associated with blood group O • Occurs in 20% of patients after an acute PE • Should be treated initially by Thrombolysis • The diagnosis mandates placement of an IVC filter • There is an increased risk of developing CTEPH associated with CSF shunt placement
Pulmonary Hypertension The following are recognised causes of pulmonary hypertension. • Schistosomiasis • Sickle cell disease • Malaria • Cytomegalovirus • Mitral stenosis
Pulmonary Hypertension A 25 year old female presents with a short 3 month history of progressive breathlessness and exertional chest pain with syncope. The cardiologist immediately arranges a cardiac catheter. Left sided pressures are normal RHC pressures are as follows (mmHg) Mean PA 60 RA 12 PCW 8 and CO is 2.8 L/min Which of the following statements are true • The diagnosis is iPAH and no other investigations are required • There is no clinical role for genetic testing • Heart Lung Transplantation should be considered • A trial of high dose Nifedipine should be considered • Her history of developing high altitude sickness when climbing Mt Kilimanjaro during a gap year is irrelevant
Transplantation The most likely underlying diagnosis is A Disseminated nocardiasis B Disseminated aspergillosis C Small cell lung cancer of donor lung origin D Post transplant lymphoproliferative disease E Unknown primary carcinoma A 40 year old man is admitted with severe abdominal pain nine months after bilateral lung transplantation for IPF. His CXR the week before organized by his GP for malaise is shown in figure A His admission erect abdominal film is shown.
PTLD • Usually B cell origin • Early and late presentation (organ transplanted) • Clonality and grade determines therapy • Associated with EBV commonly • Reduce Immunosuppression Rituximab CHOP etc
Transplantation What is single most appropriate advice to give the patient ? A Mycobacterium abscessusis an absolute contraindication to lung transplantation B The presence of this organism confers no added risks for transplantation C The organism must be eradicated prior to transplant referral D Appropriate multidrug antimicrobial therapy should be started E There is a need to undertake BAL to confirm the pathogenic presence of this organism 29 year old man with advanced CF is being prepared for transplant referral. Sputum cultures are positive for Mycobacterium abscessus on 3 occasions
NTM • All CF patients should be screened pre referral • Presence according to guidelines • Molecular typing • Abscessus species problematic • Treat pre referral and continue after transplant ? indefinitely • Multi drug regimen marked drug toxicity • Other NTM much less problematic
Transplantation What is the most likely diagnosis ? A Bronchiolitis obliterans B Acute rejection C Recurrence of his emphysema D Lymphocytic bronchiolitis E Stricture of anastomosis in main bronchus His PEF is A 300 L/min B 180 L/min His MMEF is A > 100 L/min B < 60 L/min A 54 year old man who underwent single lung transplantation for emphysema and alpha 1 antitrypsin deficiency six months previously presents with increasing breathlessness. A flow volume curve shows the appearances above
Transplantation • A 60 year old obese woman with advanced IPF whose BMI is 35 is referred for transplantation. Which one answer below is true ? A She has an increased risk of primary graft dysfunction if accepted and undergoes transplantation B She has no added risks of an adverse outcome providing there are no other relative contraindications C She has 50% less chance of surviving 5 years compared with a 35 year old with a BMI of 24 D She can only be considered for bilateral lung transplantation E She can only be considered for single lung transplantation
Transplantation • A 25 year old woman with cystic fibrosis who has stable lung function and no evidence of BOS 5 years following lung transplantation tells you she is 3 months pregnant. She has a GFR of 50 mls/min. Which of the following statements are correct A She should be advised that continuing her pregnancy is too dangerous for her and her babies health to support on medical grounds B She should be advised that the risk of her delivering a child without serious birth defect is only 20% C She should be advised to stop her immunosuppression immediately D She should be advised that she is at high risk of developing renal failure if her pregnancy continues E She should be advised she has a greater than 50% chance of developing pre eclampsia before she reaches 40 weeks
The Journal of Heart and Lung Transplantation Volume 33, Issue 6, June 2014, Pages 593–598 Original Clinical Science Pregnancy after lung and heart-lung transplantation Mitesh V. Thakrar, MDa, b, , , Katie Morley, RNa, James L. Lordan, MDa, Gerard Meachery, MDa, Andrew J. Fisher, MDa, Gareth Parry, MDa, Paul A. Corris, MDa
Transplantation • Which of the following statements is/are true of all surviving recipients 5 years post Lung Transplantation? A 40% have developed hypertension B 25% have evidence of renal dysfunction C 40% have diabetes D 20% have dyslipidaemia E 70% have Bronchiolitis Obliterans Syndrome (BOS)
Transplantation • A 29 year old man with CF who is negative for CMV serologically received lungs from a donor who was CMV positive. Which of the following statements is/are true ? A Transplantation should not have been carried out because all patients have to be CMV matched B Post operative blood transfusion should have utilised irradiated blood to ensure viral transfer does not occur C The patient should be given valgancicloviras soon as symptoms of CMV infection occur typically at 14 days D CMV hyperimmune globulin should be given twice weekly for 3 months E Prophylactic valganciclovir should be given immediately for at least 3 months
Transplantation • 50 year old patient who received bilateral lung transplantation for iPAHand was very well presents at 12 months with acute onset fever cough and breathlessness . She is hypoxic and has CXR above. Her creatinine is 150. Which of the following is/are True A Acute rejection is most likely diagnosis B Patient should have a CTPA since PE most likely C Pneumocystis infection is most likely D Therapy should be commenced empirically using high doses of both apenicillin and macrolide E Therapy should be commenced empirically with a penicillin and a quinalone
Transplantation (Exam) • Which of the statements below is/are true ? • Donor lungs have to be both ABO compatible and tissue type matched for the recipient to receive donor lungs . • Patients who are HIV positive have an absolute contraindication to lung transplantation. • Long term results of bilateral lung transplantation are better than single lung transplantation in patients with COPD • A potential recipient should have class 1 and class 2 HLA antibody status measured pre listing. • The GFR of a potential recipient should be greater than 50 mls/min before accepting a patient for lung transplantation.
Transplantation (Exam) A 27 year old man with CF presents with acute abdominal pain, malaise, breathlessness and fever 18 weeks after lung transplantation. His routine 12 week biopsy showed no evidence of rejection. He has new onset leucopenia and looks unwell. CT scan is as above. He was a CMV negative recipient of an organ from a CMV positive donor and is on prophylactic valganciclovir. • Which statements is/ are true • He most likely has acute vascular rejection and should have iv steroids empirically • He most likely has CMV disease and should initially have empirical treatment dose valganciclvir and PCR of blood to quantify CMV viral load. • He should be scheduled for urgent bronchoscopy with biopsy and lavage • CMV pneumonitis is best diagnosed by PCR of BAL fluid. • He most likely has pseudomonal pneumonia
Transplantation (Exam) • A 58 year old patient with IPF and UIP on lung biopsy and traction bronchiectasis reported on CT with a mean pulmonary artery pressure of 30 mmHg is referred for transplant assessment. Which statements is/are true? • He has a better survival outlook in UK after listing if he is offered single lung transplantation. • He is only suitable for consideration of bilateral lung transplantation. • He should receive treatment with targeted PH therapy if placed on waiting list • He should be routinely listed to have cardiopulmonary bypass if accepted for transplant surgery. • He is not a suitable candidate for transplant surgery.
Transplantation (Exam) • A 49 year old woman otherwise fit with severe PiZZ associated emphysema and an asymptomatic 20% stenosis of her LAD coronary artery and no pressure change across the lesion is referred for transplantation. Which statement below is true ? • She should be offered heart lung transplantation . • She should be offered single lung transplantation after coronary stenting. • She should be offered bilateral lung transplantation after coronary stenting. • She should be offered bilateral lung transplantation without need for stenting • She is not suitable for further consideration of transplantation.
Pulmonary Physiology T or F A 34 year old male presents with breathlessness and has widespread alveolar shadowing. His arterial PaO2 is 5.5 Kpa and PaCO2 3.2 Kpa breathing air. VC is 60% predicted and TLCO is 150% predicted • The blood gases are more likely to be venous • His A-a gradient is >10 Kpa • Most likely he has cardiogenic pulmonary oedema • He should be managed on an HDU • He should initially be given 24% oxygen via venturi mask
Pulmonary Physiology • The Total lung capacity as measured by body plethysmography is determined by inspiratory muscle strength and recoil pressure of the lung • Lung fibrosis results in a reduced lung compliance and increased recoil pressure • The hypoxia seen at rest in lung fibrosis is principally due to impaired gas exchange due to the thickened alveolar walls • Flow is constant throughout expiration during a maximal effort • Peak flow shows diurnal variation in normal subjects
Pulmonary Physiology A 44 year old chronically breathless patient has an FEV1 of 30%p an FVC 0f 60% p a TLC of 250%p and a TLCO of 25% p • He has mixed obs. restrictive disease • He most likely has asthma • His VC (relaxed) is most likely to be greater than his FVC • His RV is most likely to be normal • The physiology is typical of advancedLangerhans Cell Granulomatosis
Pulmonary Physiology Cardiopulmonary exercise test in a 37 yr old female shows a VO2P of 65% pred. HR max was 70% pred. And VE max was 50% pred. The RER at the end of exercise was 0.9 and lactate was 1.2 • The test was limited by the onset of premature anaerobic respiration • The test was limited by respiratory disease • The result suggests a mitochondrial myopathy • The test indicated a cardiac limitation to exercise • The test results are in keeping with a suboptimal effort
Pulmonary Physiology In normal human subjects • Tidal volume increases before respiratory rate on exercise • The increase in ventilation is linear until nearing maximum • Expiratory flow is principally governed by lung recoil pressure during tidal breathing • The intercostal muscles principally determine inspiratory volume • I am as confident of success in the exam as the England cricketteam has of success in next test at Lords