Πνευμονική Αρτηριακή Υπέρταση

Πνευμονική Αρτηριακή Υπέρταση Αλλαγές στη διαγνωστική προσέγγιση και στο screening ομάδων υψηλού κινδύνου Ελένη Τριανταφυλλίδη Επιμελήτρια A Β Πανεπιστημιακή Καρδιολογική Κλινική Νοσοκομείο ΑΤΤΙΚΟΝ 36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015

There is no conflict of interest 36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015

The term PAH describes a group of PH patients characterized haemodynamically by the presence of pre-capillary PH, defined by a pulmonary artery wedge pressure (PAWP) 15 mmhg and a PVR >3 Wood units (WU) in the absence of other causes of pre-capillary PH such as PH due to lung diseases, CTEPH or other rare diseases. 36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015

36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015

Epidemiology and risk factors The lowest prevalence of PAH and IPAH are 15 cases and 5.9 cases/million adult population. The lowest estimate of PAH incidence is 2.4 cases/million adult population/year. In Europe, PAH incidence is in the range of 15 60 subjects/million population and 5 10 cases/ million/year. Half of PAH patients have idiopathic, heritable or drug-induced PAH while in APAH the leading cause is CTD, mainly Systemic Sclerosis. IPAH corresponds to sporadic disease, without any familial history of PAH or known triggering factor. While the mean age of patients with IPAH in 1981 (NIH) was 36 years, PAH is now more frequently diagnosed in elderly patients (50-65 years). Furthermore, the female predominance is quite variable among registries and may not be present in elderly patients, and survival appears to have improved over time. 36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015

36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015 Pulmonary hypertension diagnosis

36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015 Pulmonary hypertension diagnosis

Echocardiography The estimation of systolic PAP is based on TRV taking into account RAP (based on the diameter and respiratory variation in diameter of the IVC): IVC diameter <2.1 cm that collapses >50% with a sniff suggests a normal RA pressure of 3 mmhg (range 0 5 mmhg), IVC diameter >2.1 cm that collapses <50% with a sniff or <20% on quiet inspiration suggests a high RA pressure of 15 mmhg (range 10 20 mmhg). In scenarios in which the IVC diameter and collapse do not fit this paradigm, an intermediate value of 8 mmhg (range 5 10 mmhg) may be used. However, given the inaccuracies of RAP estimation we recommend using the CW Doppler measurement of peak TRV as the main variable for assigning the echocardiographic probability of PH. 36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015

36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015 Echocardiography

36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015 Pulmonary hypertension diagnosis

High-resolution computed tomography Cardiac magnetic resonance imaging CT imaging can provide important information on vascular/cardiac/parenchymal/mediastinal abnormalities. CT may raise a suspicion of PH in symptomatic patients or those examined for unrelated indications by showing an increased PA diameter 29 mm and pulmonary:ascending aorta diameter ratio 1.0. In PH it may: suggest diagnosis (PA or RV enlargement), identify a cause (CTEPH or lung disease), provide clues as to the form of PAH (oesophageal dilation in SSc or congenital cardiac defects such as anomalous pulmonary venous drainage) and also provide prognostic information. HRCT may also be very helpful where there is a clinical suspicion of PVOD (interstitial oedema with diffuse central ground-glass opacification and thickening of interlobular septa, lymphadenopathy, pleural shadows and effusions). However, ground-glass abnormalities are also present in PAH, occurring in more than one-third of patients. MRI leads to assessment of RV size, morphology and function and allows non-invasive assessment of blood flow, including stroke volume, CO, pulmonary arterial distensibility and RV mass. 36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015

36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015 Pulmonary hypertension diagnosis

Ventilation/perfusion lung scan The ventilation/perfusion (V/Q) lung scan has been the screening method of choice for CTEPH because of its higher sensitivity compared with CTPA, especially in inexperienced centres. A normal- or low-probability V/Q scan effectively excludes CTEPH with a sensitivity of 90 100% and a specificity of 94 100%. However, many V/Q scans are not diagnostic. While in PAH the V/Q lung scan may be normal, it may also show small peripheral unmatched and non-segmental defects in perfusion. 36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015

36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015 Pulmonary hypertension diagnosis

Right heart catheterization and vasoreactivity Cardiac catheterization should be performed after the completion of other investigations so that it can answer specific questions that may arise from these investigations and avoid an unnecessary procedure where an alternative diagnosis is revealed. A PVR >3 WU is required for the diagnosis of PAH. The DPG is less affected by flow and filling pressures, may not be of prognostic value but have a role in patients suspected of having PH related to LHD. Pulmonary vasoreactivity testing for identification of patients suitable for highdose CCBs is recommended only for patients with IPAH, HPAH or drug-induced PAH. Inhaled NO at 10 20 parts per million (ppm) is the standard but i.v. epoprostenol, i.v. adenosine or inhaled iloprost can be used as alternatives. A positive acute response is defined as a reduction of the mean PAP 10 mmhg to reach an absolute value of mean PAP 40 mmhg with an increased or unchanged CO. Only about 10% of patients with IPAH will meet these criteria. The use of CCBs, O 2, PDE-5 inhibitors or other vasodilators is discouraged. 36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015

Right heart catheterization and vasoreactivity 36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015

36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015 Pulmonary hypertension diagnosis

36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015 Classifications

Reduced BMPR2 expression (bone morphogenetic protein receptor 2) contributes to the pathobiology of heritable and other forms of PAH. Genetic counselling and BMPR2 mutation screening should be offered by referral centers to patients with IPAH considered to be: i. sporadic <40 years old ii. induced by anorexigens iii. patients with a family history of PAH. When no BMPR2 mutations are identified in familial PAH patients or in IPAH patients <40 years old, or when PAH occurs in patients with a personal or familial history of hereditary haemorrhagic telangiectasia, screening of the ACVRL1 and ENG genes may be performed. 36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015 Genetic testing

36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015 Exercise capacity Biochemical markers The 6MWT, a submaximal exercise test, remains the most widely used exercise test in PH centres (easy to perform, inexpensive and familiar to patients and centres). Absolute values, but not changes in 6MWD, provide prognostic information, but there is no single threshold that is applicable for all patients. CPET is usually performed as a maximal exercise test and provides important information on exercise capacity as well as on gas exchange, ventilator efficacy and cardiac function during exercise. So far BNP and NT-proBNP remain the only biomarkers that are widely used in the routine practice of PH centres as well as in clinical trials. BNP appears to have a slightly tighter correlation with pulmonary haemodynamics and is less affected by kidney function, whereas NT-proBNP seems to be a stronger predictor of prognosis

Comprehensive prognostic evaluation and risk assessment The most important questions to be addressed at each visit are (i) (ii) (iii) (iv) is there any evidence of clinical deterioration since the last assessment? if so, is clinical deterioration caused by progression of PH or by a concomitant illness? is RV function stable and sufficient? is the current status compatible with a good long-term prognosis, i.e. does the patient meet the low-risk criteria. 36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015

Comprehensive prognostic evaluation and risk assessment 36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015

Pulmonary arterial hypertension screening program Prognosis of PAH is significantly worse in patients with advanced disease. PAH therapies delay clinical worsening and early treatment improves long-term outcome. Screening is the systematic application of a test to identify individuals at sufficient risk of a specific disorder to warrant further investigation or direct preventive action among persons who have not sought medical attention on account of symptoms of that disorder. Therefore screening for PH/PAH applies to asymptomatic individuals belonging to groups in which PH/PAH is highly prevalent: patients with systemic sclerosis (SSc), BMPR2 mutation carriers or relatives of patients with heritable PAH, patients with sickle cell disease (SCD) and patients with portal hypertension referred for liver transplantation.

Pulmonary arterial hypertension screening program 36 ο Πανελλήνιο Καρδιολογικό Συνέδριο, Θεσσαλονίκη 2015