***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Chronic thromboembolic pulmonary hypertension ( CTEPH ) is a rare but potentially life-threatening disease of the pulmonary circulation [ 1 ] . The pathogenesis of CTEPH is not entirely clear . The most accepted scenario is that of aborted recanalisation of pulmonary arteries after a thromboembolic episode . While some post-embolic residua may persist in up to 50 % of survivors of acute pulmonary embolism ( aPE ) , only 0.5 % to 2 % will progress to CTEPH [ 2 , 3 ] . This is believed to occur in the presence of significant redistribution of flow to remaining unoccluded pulmonary bed with result ing elevation of intravascular pressure and shear stress . Remodelling of initially patent pulmonary arterioles leads to an increase in pulmonary vascular resistance similar to that observed in left-to-right shunting in congenital heart disease . Progressive uncoupling of pulmonary and right ventricular elastance results in a fall of pulmonary flow , left ventricular preload , systemic blood pressure , and right ventricular ( RV ) coronary perfusion leading to right heart failure with severe functional disability and eventually to death . Management of CTEPH requires precise differential diagnosis and qualification for surgical treatment by an experienced multidisciplinary team . Indeed , in operable patients  pulmonary endarterectomy ( PEA ) is highly effective in restoring functional status and improving life expectancy . A surgical technique has been optimised and implemented worldwide by a group from San Diego – University of California [ 4 ] . Nevertheless , PEA performed in deep hypothermia and intermittent total cardiac arrest remains one of the most dem and ing cardiovascular interventions and is performed only in a limited number of highly dedicated centres . As an example , Papworth Hospital is the only centre performing PEA in the UK , while Marie-Lannelongue Hospital in Paris remains a referral centre for France for this type of surgery . Usually , individual cardiac surgeons are responsible for PEA in their centres , as the learning curve for this intervention has been well documented [ 5 ] . With growing experience of clinicians , radiologists , surgeons , and anaesthesiologists , an increasing proportion of patients with CTEPH may benefit from PEA despite distal , less accessible intravascular residua and /or advanced age and comorbidities . This is of paramount importance since the outcome of non-operated patients is drastically worse ( Figure 1 ) , despite identical baseline haemodynamic characteristics and significant perioperative mortality of 2–10 % in patients su bmi tted to PEA [ 6 ] . Nevertheless , even in the leading CTEPH referral centres almost 50 % patients remain on medical treatment alone , with grim perspectives regarding life quality and expectancy . Based on a large r and omised trial and promising long-term effects on exercise tolerance [ 7 , 8 ] direct guanylyl cyclase stimulator ( riociguat ) has been approved for treatment of inoperable CTEPH .  Riociguat may protect patent pulmonary arterioles from progressive remodelling [ 9 ] but is unlikely to affect the culprit post-embolic residua . Recently , balloon pulmonary angioplasty ( BPA ) has emerged as a promising new interventional option in non-operable CTEPH . In 2001 , Feinstein et al. from Harvard Medical School described a group of 18 CTEPH patients treated with BPA [ 10 ] . Of these , 16 were excluded from PEA due to distal lesions , and two due to the presence of comorbidities increasing the risk associated with surgical treatment . In total , 47 procedures were performed , thus dilating or restoring the patency of 107 arteries . In the periprocedural period , 1 patient died of reperfusion pulmonary oedema and right ventricular failure . In total , reperfusion oedema occurred in 23 % of cases , and its presence correlated with the value of pulmonary artery pressure ( PAP ) prior to the procedure . Long-term follow-up ( mean , 34 months ) showed an increase in physical capacity , manifesting itself as an improvement in NYHA class from a mean value of 3.3 prior to the procedure to a mean value of 1.8 following the procedure . Figure 1 Survival curves for patients with CTEPH treated with PEA ( shadow line ) and who were treated by pharmacotherapy only ( solid line ) – reprinted from Wieteska et al. [ 6 ] The succeeding years saw the development of the BPA technique mainly in Japanese centres . Japanese research ers have refined the BPA technique by reducing the number of segments treated during one session [ 11 ] , by using smaller balloons [ 12 ] , and by wider use of intravascular imaging [ 13 , 14 ] . The experience of the Japanese centres shows that a series of BPA procedures performed in experienced centres has lead to regression of right ventricular dysfunction [ 15 , 16 ] and are associated with an annual mortality below 5 % – also in elderly patients [ 17 ] . However , it should be stressed that the population of Japanese patients with CTEPH differs from that observed in the European-American registry [ 18 ] . In a registry comprising 519 Japanese patients with CTEPH , lower median pretreatment mPAP ( 38 mm Hg vs. 47 mm Hg ) , more frequent use of PAH-like therapy ( 52 % vs. 38 % ) , and a significantly lower rate of cardiac surgical treatment used ( 14 % vs. 57 % ) was observed [ 19 ] . The only larger group of patients in Europe who underwent BPA is that described by And reassen et al. [ 20 ] . The Norwegian team treated 20 CTEPH patients , including 16 with distal lesions , 3 with proximal lesions who had refused PEA , and 1 patient with persistent pulmonary hypertension following surgical treatment . Prior to treatment , 85 % of the patients presented with NYHA class III and IV symptoms . During recruitment to a percutaneous treatment program in the same centre , 50 PEAs were performed . In total , 73  BPA procedures were carried out ( mean , 3.7 BPAs/patient ; range : 2–9 ) , thus performing angioplasty of 371 vessels – 118 segmental arteries and 253 subsegmental arteries . In the periprocedural period , two patients died , and treatment-requiring reperfusion oedema occurred in 7 cases . During 3-month follow-up , an improvement in the functional class ( 75 % of patients in NYHA class I – II ) , in VO2max in cardiopulmonary exercise test ( 13.6 ±5.6 vs. 17.0 ±6.5 , p < 0.001 ) , in mean pulmonary artery pressure ( 45 ±11 mm Hg vs. 33 ±10 mm Hg , p < 0.001 ) , in pulmonary vascular resistance ( 8.8 ±4.0 Wood Units vs. 5.9 ±3.6 Wood Units , p < 0.001 ) , and in NT-pro-BNP levels ( 194 ±182 ng/ml vs. 90 ±119 ng/ml , p = 0.007 ) was achieved . Follow-up angiography revealed no restenosis . In Pol and , the first BPA procedure was performed in 2013 [ 21 ] . Until now , the experience of our team includes 37 BPA procedures , which consisted of angioplasty of 105 vessels in 20 patients with CTEPH . Seventeen patients were excluded from surgical treatment by an experienced PEA cardiac surgery team , and in 3 patients persistent pulmonary hypertension persisted after PEA . Eighty-two percent of patients received PAH-like therapy – most frequently sildenafil . In the periprocedural period , two patients died of severe reperfusion oedema and severe hypoxaemia unresponsive to oxygen therapy ( including mechanical ventilation ) . Those 2 patients were disqualified from PEA due to the presence of  extensive lung cavities  related to previous mycobacterial infection and due to significant comorbidities and advanced age , respectively – but not because of distal localisation of thrombi . All patients who underwent BPA because of distal lesion localisation survived . In technical terms , BPA does not significantly differ from balloon angioplasty performed in other vessels ( Figure 2 ) . Nevertheless , the complicated anatomy of the pulmonary tree , the necessity to advance the instruments through enlarged right heart chambers , and the fact that pulmonary vessels can be easily damaged with the guide wire or balloon catheter requires specific experience . It is not recommended that BPA procedures be performed by cardiologists or interventional radiologists who have experience in other vascular regions but no experience in interventions within the pulmonary circulation . During one procedure , no more than two segmental arteries or their subsegmental equivalents should be dilated due to the risk of reperfusion oedema . Reperfusion oedema results from redistribution of blood flow to areas supplied by dilated vessels , in which vascular resistance has abruptly decreased . This may cause blood cells to migrate into the alveoli , excluding them from gas exchange . One way to prevent reperfusion oedema is to undersize the balloon catheter being used , on the basis of angiography , or by means of intravascular ultrasound ( IVUS ) or optical coherence tomography ( OCT ) . Also , pressure distal to a residual lesion and a gradient across the lesion can be measured by means of an fractional flow reserve ( FFR ) probe [ 22 ] . As there is no tendency towards restenosis , it is unnecessary to use stents . The results achieved in the group of patients who have completed a series of BPA procedures are very encouraging . A reduction in mean PAP from baseline 58 ±6 mm Hg to 41 ±9 mm Hg and in PVR from 11.7 ±4.3 Wood units to 6.6 ±2.2 Wood units was achieved in our series . The haemodynamic improvement corresponds with an improvement in exercise tolerance . Prior to BPA procedures , 95 % of patients were in NYHA class III and IV , and the rate of patients in class III and IV decreased to 35 % after treatment . A significant issue limiting growth in the number of such procedures performed in Pol and is that BPA is not reimbursed by the National Health Fund . Figure 2 Balloon pulmonary angioplasty in a 67-year-old patient with persistent form of CTEPH . Left panel ( A ) presents the angiogram of occluded segmental pulmonary artery of left lower lobe . The BPA results in reperfusion of the vessel – right panel ( To use cardiac magnetic resonance imaging ( MRI ) to investigate the effect of balloon pulmonary angioplasty ( BPA ) on interventricular dyssynchrony and its associations with ventricular interaction , which impairs LV function in patients with inoperable chronic thromboembolic pulmonary hypertension ( CTEPH ) . This prospect i ve observational study was approved by our institutional review board . Cardiac MRI and right heart catheterization were conducted before BPA sessions and at the follow up after BPA in 20 patients with CTEPH . We measured right ventricular ( RV ) and left ventricular ( LV ) end-diastolic volume ( EDV ) , end-systolic volume ( ESV ) , stroke volume ( SV ) , and ejection fraction ( EF ) using MRI . For the LV and RV free walls , the time to peak ( Tpeak ) of circumferential strain was calculated as a parameter for interventricular dyssynchrony . Following BPA , the RV-EDV and -ESV were significantly decreased , and the RVEF was significantly increased . Conversely , BPA led to significantly increased LV EDV and SV without changing LVESV . The left-to-right free wall delay ( L – R delay ) in Tpeak strain decreased from 105 ± 44 ms to 47 ± 67 ms ( p < 0.001 ) . Increased LV EDV ( r = 0.65 , p < 0.01 ) , SV ( r = 0.74 , p < 0.001 ) and 6-minute walk distance ( 6MWD ) ( r = 0.54 , p < 0.05 ) were correlated to the reduction in L – R delay . In patients with inoperable CPEPH  , BPA improved interventricular dyssynchrony , which was strongly associated with increased SV and 6MWD . The assessment of interventricular dyssynchrony using cardiac MRI has an important role in evaluating ventricular interaction , which reduces LVSV and exercise tolerance BACKGROUND Although balloon pulmonary angioplasty ( BPA ) improves the hemodynamics and prognosis of patients with inoperable chronic thromboembolic pulmonary hypertension ( CTEPH ) , the mechanisms of improvement in oxygenation remain to be eluci date d. METHODS AND RESULTS From August 2013 to May 2015 , we performed a total of 113 BPA procedures in 24 patients with inoperable CTEPH ( mean 4.7 procedures per patient ) . Median age was 70 [ 60 , 74 ] years and 18 were female ( 75 % ) . We examined hemodynamics , respiratory functions , and intrapulmonary shunt before and after the BPA  procedure . Mean pulmonary arterial pressure ( 37 [ 28 , 45 ] to 23[19 , 27 ] mmHg , P<0.01 ) , pulmonary vascular resistance ( 517 [ 389 , 696 ] to 268 [ 239 , 345 ] dyne/s/cm(5 ) ) and 6-min walk distance ( 390 [ 286 , 484 ] to 490 [ 411 ,  
    Output:
    
The most common adverse events of riociguat  were headache , dizziness , hypotension and nasopharyngitis .
CONCLUSIONS Our meta- analysis indicates that BPA might be associated with greater improvements in exercise tolerance and pulmonary hemodynamics except for cardiac output and cardiac index than riociguat therapy .
However , both of them were well tolerated