Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening complication which develops mainly in the first two years after an acute pulmonary embolism (APE). It is the only form of PH with a resolutive treatment. Early diagnosis of CTEPH is essential, as delay in diagnosis may be associated with a worse prognosis and higher perioperative mortality. Nevertheless, a screening program is not available yet, due to the low incidence of the pathology and the lack of adeguate screening tools. The possibility to identify patients at high risk of CTEPH development would improve the chance of applying targeted follow up programs.
Most of data on risk factors and screening tools come from small monocentric studies or retrospective studies or registries.
We will analyze data from CTEPH SOLUTION database, a transverse and prospective multicenter observational study involving 27 Italian centers affiliated with IPHNET (Italian Pulmonary Hypertension NETwork). Clinical, radiological and for the first time echocardiographic data of patients with previous episodes of pulmonary embolism confirmed at angioCT and/or pulmonary scintigraphy will be collected up to a total of 1000 patients, followed up for 1 year. The study will be completed in December 2020. I will have the unique opportunity to analyze for the first time the study data focused on the right ventricle evaluation by echocardiography.
EU encourages researchers to focus on rare diseases to allow the health system to efficaciously match those patients characterized by increased frailties and recommends to invest in rare diseases as a major research priority to be addressed in the near future.
This study aims to investigate the incidence of CTEPH after PE in a large cohort of patients and to determine echocardiographic predictors of CTEPH in order to identify patients at higher risk of developing CTEPH, thus facilitating the future application of a follow up program in this setting.
Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is considered to be the most serious longterm complication of acute PE. It is the only form of PH potentially curable for operable patients. Non operable patients are associated with high morbidity and mortality, with a poor prognosis (5-year survival rates 30% in untreated patients). The diagnostic delay in fact may be associated with a progressive small vessel changes resulting in worse prognosis and higher perioperative mortality rate for operable patients.
Its incidence is limited to the first 2 years after the embolic event, therefore an early diagnosis of the disease should be mandatory.
Current European Society of Cardiology guidelines do not recommend to screen all survivors of PE, limiting subsequent diagnostic tests to patients who remain symptomatic.
However CTEPH is often underdiagnosed or misdiagnosed as idiopathic pulmonary arterial hypertension (PAH) due to a lack of clinical suspicion (aspecific symptoms) and the rarity of the disease.
So far, the reported risk factors for CTEPH are somehow inconsistent and not validated.
Current evidence suffers from several limitations: patient cohorts are heterogeneous and their mortality rates variable; studies are often retrospective and not adequately controlled; the severity of the initial embolic episode is often unknown; and it is very hard to exclude pre-existing PH.
Echocardiogram is a rapid, low-cost exam, indicated in patients diagnosed with PE for risk stratification and with an extremely favorable cost/benefit ratio. To our knowledge two studies demonstrated the predictive role of echocardiographic variables at the time of diagnosis of PE in the prediction of development of CTEPH, both with few patients.
Despite its key role in PE diagnosis and risk stratification echochardiogram is not included in the few predictive scores for CTEPH development, partly due to the difficulty in collecting echo data at the time of the event.
The only available study on echocardiography included in a predictive score for CTEPH development comes by Klock et al. from a post-hoc analysis of three large prospective cohorts. However it considers just qualitative assessment of RV disfunction by echo or CT scan and suffers from all post hoc analysis limitations.
The CTEPH SOLUTION (Chronic ThromboEmbolic Pulmonary Hypertension risk ScOre evaLUation and validaTION; approved on 18/12/2014; registry number: 3465) study, currently ongoing among the Italian Pulmonary Hypertension NETwork (IPHNET) includes several relevant echocardiographic variable (RV diastolic diameters, tricuspid annular plane systolic excursion, tricuspid valve regurgitation, peak gradient, inferior vena cava dimensions and collapsibility, fractional area of change (FAC) and right atrium area) calculated at the time of the acute pulmonary event , at hospital discharge, at 6 months and 1 year follow up among all the other clinical and hemodynamic variable known to be significant in previous scores.
This is the first large prospective study on CTEPH development prediction in patients with PE, aiming at a comprehensive scoring tool that includes imaging echocardiographic data.
In our opinion this study has the potential to overcome the few previous studies available.
The possibility to realize a validated screening tool may allow for early CTEPH diagnosis and the application of follow up screening programs for patients with PE.