Distal Chronic Thromboembolic Pulmonary Hypertension Research Articles

Effects of 5-Week Oral Acetazolamide on Incremental Cycling Exercise in Pulmonary Arterial and Chronic Thromboembolic Pulmonary Hypertension: A Randomized Placebo-Controlled, Double-Blinded, Crossover Trial

Introduction: Acetazolamide (AZA) improves nocturnal and daytime blood oxygenation in patients with pulmonary vascular disease (PVD), defined as pulmonary arterial and distal chronic thromboembolic pulmonary hypertension (CTEPH), and may improve exercise performance. Methods: We investigated the effect of 5 weeks of AZA (250 mg bid) versus placebo on maximal load during incremental cycling ramp exercise in patients with PVD studied in a randomized controlled, double-blind, crossover design, separated by > 2 weeks of washout. Results: Twenty-five patients (12 pulmonary arterial hypertension, 13 CTEPH, 40% women, age 62 ± 15 years) completed the trial according to the protocol. Maximum load was similar after 5 weeks of AZA versus placebo (113 ± 9 vs. 117 ± 9 watts [W]), mean difference −4 W (95% CI: −9 to 1, p = 0.138). With AZA, maximum (max)-exercise partial pressure of O₂ (PaO₂) was significantly higher by 1.1 kPa (95% CI: 0.5–1.8, p = 0.003), while arterial pH and partial pressure of CO₂ were significantly lower. Gas exchange threshold was reached at a higher load with AZA (108 ± 8 W vs. 97 ± 8 W) and was therefore delayed by 11 W (95% CI: 3–19, p = 0.013), while the ventilatory equivalent for O₂ and CO₂ were significantly higher at both the max-exercise and gas exchange threshold with AZA versus placebo. Conclusion: AZA for 5 weeks did not significantly change maximum exercise capacity in patients with PVD despite a significant increase in PaO₂. The beneficial effects of increased blood oxygenation may have been diminished by increased ventilation due to AZA-induced metabolic acidosis and increased dyspnea.

Predictors of therapeutic response to specific therapy in distal chronic thromboembolic pulmonary hypertension

Aim. To assess therapeutic response to specific therapy in patients with distal CTEPH who are ineligible for surgical management as pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA).Materials and methods. The study included inoperable patients with CTEPH (n=53) who are ineligible for surgical management as pulmonary endarterectomy or balloon pulmonary angioplasty. The effectiveness of specific therapy were assessed after dividing the patients into improvement or nonimprovement groups based on the following indicators: functional class I-II (WHO), mean pulmonary artery pressure according to right heart catheterization ≤40 mm Hg, pulmonary vascular resistance ≤400 dyn×s×cm-5, cardiac index ≥2,5 L/min/m2 , decrease in N-terminal brain natriuretic peptide >30%, and increase in 6-minute test distance >30 m at 12th-month follow-up compared to baseline parameters.Results. There were no differences in groups by gender, age, and received specific therapy. Multiple logistic regression was performed, resulting in a model for predicting clinical improvement with sensitivity (57,1%) and specificity (87,1%), p=0,002. It was revealed, that the absence of the loss of pulmonary vascularity by X-ray at the time of verification of the diagnosis in patients with CTEPH by 5,91 times increases the chance of achieving clinical improvement after 12 months of the specific therapy, while the absence of signs of heart failure by 5,79 times, and degree of pulmonary valve insufficiency 0-1 according to echocardiography by 9,2 times, respectively.Conclusion. Early initiation of specific therapy in inoperable CTEPH patients due to distal lesions with the absence of severe vascular remodeling and heart failure symptoms leads to the better therapeutic response after 12 months of treatment.

Balloon pulmonary angioplasty outcomes in patients previously treated by pulmonary endarterectomy surgery are inferior to those of inoperable patients

AbstractPulmonary endarterectomy (PEA) may not achieve full clearance of vascular obstructions in patients with more distal chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) may be indicated to treat these residual vascular lesions. We compared whether patients post‐PEA (PP) treated by BPA derived similar benefit to those who had inoperable CTEPH (IC), and assessed predictors of BPA response after surgery. We treated 109 patients with BPA—89 with IC and 20 PP. Serial right heart catheterization performed at baseline (immediately before BPA) and 3 months after completing BPA, compared pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP) as well as change in WHO functional class and 6‐minute walk distance. We also assessed the impact of total thrombus tail length (TTTL) from photographed PEA surgical specimens and PP computed tomography pulmonary angiography (CTPA)‐quantified residual disease burden on BPA response. PP and IC groups did not differ significantly in terms of demographics, baseline hemodynamics or procedural characteristics. However, IC derived greater hemodynamic benefit from BPA: ΔPVR (−27.9 ± 20.2% vs. −13.9 ± 23.9%, p < 0.05) and ΔmPAP (−17.1 ± 14.4% vs. −8.5 ± 18.0%, p < 0.05). There was a negative correlation between pre‐BPA PVR and TTTL (r = −0.47, p < 0.05) which persisted post‐BPA. PVR, mPAP, WHO FC and 6MWD were not improved significantly post‐BPA in PP patients. BPA response was not related to TTTL terciles or CTPA‐quantified residual disease burden. Patients PP experienced inferior response to BPA, despite similar baseline and procedural characteristics to IC. BPA does not abolish the relationship between TTTL and postsurgical PVR in PP patients, suggesting that BPA is less effective in treating residual PH after surgery in an experienced surgical center.

Pulmonary Vein Sign on Computed Tomography Pulmonary Angiography in Proximal and Distal Chronic Thromboembolic Pulmonary Hypertension With Hemodynamic Correlation.

Pulmonary vein sign (PVS) indicates abnormal pulmonary venous flow on computed tomography pulmonary angiography (CTPA) is a frequent finding in proximal chronic thromboembolic pulmonary hypertension (CTEPH). PVS's occurrence in distal CTEPH and correlation to disease severity is unknown. Using right heart catheterization data, we evaluated the relationship between PVS and CTEPH disease distribution and severity. A total of 93 consecutive CTEPH cases with both CTPA and right heart catheterization were identified in this retrospective multi-institutional study. After excluding 17 cases with suboptimal CTPA, there were 52 proximal and 24 distal CTEPH cases. Blood flow in the major pulmonary veins was graded qualitatively. Subgroup analysis of PVS was performed in 38 proximal CTEPH cases before and after pulmonary endarterectomy. PVS was more frequent in proximal (79%) than distal CTEPH (29%) ( P <0.001). No significant difference was noted in invasive mean pulmonary artery pressure (46±11 and 41±12mmHg) or pulmonary vascular resistance (9.4±4.5 and 8.4±4.8 WU) between the 2 groups. In the subgroup analysis, PVS was present in 29/38 patients (76%) before surgery. Postoperatively, 33/38 cases (87%, P <0.001) had normal venous flow (mean pulmonary artery pressure 46±11 and 25; pulmonary vascular resistance 9.2±4.3 and 2.6 WU preop and postop, respectively). PVS is a common feature in proximal but infrequent findings in distal CTEPH. PVS does not correlate with hemodynamic severity. PVS resolution was seen in the majority of patients following successful endarterectomy.

Distal vessel pulmonary thromboendarterectomy: Results from a single institution

Chronic thromboembolic pulmonary hypertension (CTEPH) is primarily managed by pulmonary thromboendarterectomy (PTE). As advanced surgical techniques permit resection at the segmental and subsegmental level, PTE can now be curative for CTEPH mostly involving the distal pulmonary arteries. Between January 2017 and June 2021, consecutive patients undergoing PTE were categorized according to the most proximal level of chronic thrombus resection: Level I (main pulmonary artery), Level II (lobar), Level III (segmental) and Level IV (subsegmental). Proximal disease patients (any Level I or II) were compared to distal disease (Level III or IV bilaterally) patients. Demographics, medical history, preoperative pulmonary hemodynamics, and immediate postoperative outcomes were obtained for each group. During the study period, 794 patients underwent PTE, 563 with proximal disease and 231 with distal disease. Patients with distal disease more frequently had a history of an indwelling intravenous device, splenectomy, upper extremity thrombosis or use thyroid replacement and less often had prior lower extremity thrombosis or hypercoagulable state. Despite more use of PAH-targeted medications in the distal disease group (63.2% vs 50.1%, p < 0.001), preoperative hemodynamics were similar. Both patient groups exhibited significant improvements in pulmonary hemodynamics postoperatively with comparable in-hospital mortality rates. Compared to proximal disease, a lower percentage of patients with distal disease showed residual pulmonary hypertension (3.1% vs 6.9%, p=0.039) and airway hemorrhage (3.0% vs 6.6%, p=0.047) postoperatively. Thromboendarterectomy for distal (segmental and subsegmental) CTEPH is technically feasible and may result in favorable pulmonary hemodynamic outcomes, without increased mortality or morbidity.

A CASE OF PULMONARY HYPERTENSION AS A POSSIBLE EXTRACRANIAL MANIFESTATION OF MOYAMOYA DISEASE

A CASE OF PULMONARY HYPERTENSION AS A POSSIBLE EXTRACRANIAL MANIFESTATION OF MOYAMOYA DISEASE

Chronic Thromboembolic Pulmonary Hypertension Presented with Dyspnea on Exertion: A Case Report

&lt;p&gt;慢性血栓栓塞性肺高壓是一種罕見、嚴重且持續惡化的肺部血管性疾病，隨病程進展，致死率極高，儘早鑑別診斷，方能提供準確治療計劃。本文是一位67歲女性案例，因活動呼吸喘就醫， 初步臆斷為心臟衰竭合併急性惡化，入院後藉由病史詢問、檢驗及理學檢查結果顯示BNP持續上升且心電圖呈現S1Q3T3，初步懷疑可能有肺栓塞併心衰竭，故安排心臟超音波檢查，結果發現有肺動脈高壓（肺動脈壓：62.3 mmHg）與右心衰竭，安排胸部電腦斷層攝影，顯示肺動脈栓塞，隨即召開家庭會議解釋病情後，接受右心導管合併肺動脈血管攝影檢查，最終確診為遠端型慢性血栓栓塞性肺高壓併右心衰竭。經由醫療團隊評估後，治療計劃即以藥物為主，故協助申請標靶藥物Riociguat。針對此類病人，即便臨床表徵不具特異性，仍可依病史詢問、檢驗及理學檢查預測肺栓塞的可能性，之後進入影像學鑑別診斷。換言之，雖然慢性血栓栓塞性肺高壓有其高致命的危險性，倘若能及早做出診斷與治療，便能降低死亡風險。&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;&lt;p&gt;Chronic thromboembolic pulmonary hypertension is a rare, severe and continuous deterioration of pulmonary vascular disease which has high mortality rate along with disease progression. Earlier di&amp;shy;agnosis could contribute to a more accurate treatment plan. A case of 67-year-old female was admitted to hospital because of exertional dyspnea. She was initially suffering from heart failure with acute deterioration. After admission, the results of medical history inquiry, laboratory data and physical ex&amp;shy;amination revealed that BNP level kept raising and the electrocardiogram showed S1Q3T3, which pul&amp;shy;monary embolism with heart failure was suspected. Therefore, echocardiography revealed pulmonary hypertension (pulmonary artery pressure: 62.3 mmHg) and right heart failure. Pulmonary embolism was noticed on chest computed tomography. Soon after the family meeting of medical condition dis&amp;shy;cussion, the patient received right heart catheterization combined with pulmonary artery angiography, and the final diagnosed is distal chronic thromboembolic pulmonary hypertension with right heart failure. After medical team&amp;rsquo;s assessment, the treatment plan was based on armaceutical control. Thus, the target therapy of Riociguat was performed. For such type of patients, even with non-specific symptoms, the possibility of pulmonary embolism can still be predicted based on medical history, lab&amp;shy;oratory data, physical examination, and the imaging differential diagnosis. If diagnosis and treatment can be conducted as early as possible, the high mortality rate of chronic hromboembolic pulmonary hypertension can be reduced.&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

Excess ventilation and exertional dyspnoea in heart failure and pulmonary hypertension.

Increased ventilation relative to metabolic demands, indicating alveolar hyperventilation and/or increased physiological dead space (excess ventilation), is a key cause of exertional dyspnoea. Excess ventilation has assumed a prominent role in the functional assessment of patients with heart failure (HF) with reduced (HFrEF) or preserved (HFpEF) ejection fraction, pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). We herein provide the key pieces of information to the caring physician to 1) gain unique insights into the seeds of patients' shortness of breath and 2) develop a rationale for therapeutically lessening excess ventilation to mitigate this distressing symptom. Reduced bulk oxygen transfer induced by cardiac output limitation and/or right ventricle-pulmonary arterial uncoupling increase neurochemical afferent stimulation and (largely chemo-) receptor sensitivity, leading to alveolar hyperventilation in HFrEF, PAH and small-vessel, distal CTEPH. As such, interventions geared to improve central haemodynamics and/or reduce chemosensitivity have been particularly effective in lessening their excess ventilation. In contrast, 1) high filling pressures in HFpEF and 2) impaired lung perfusion leading to ventilation/perfusion mismatch in proximal CTEPH conspire to increase physiological dead space. Accordingly, 1) decreasing pulmonary capillary pressures and 2) mechanically unclogging larger pulmonary vessels (pulmonary endarterectomy and balloon pulmonary angioplasty) have been associated with larger decrements in excess ventilation. Exercise training has a strong beneficial effect across diseases. Addressing some major unanswered questions on the link of excess ventilation with exertional dyspnoea under the modulating influence of pharmacological and nonpharmacological interventions might prove instrumental to alleviate the devastating consequences of these prevalent diseases.

Association of Electrocardiographic Signs of Right Ventricular Hypertrophy and Clot Localization in Chronic Thromboembolic Pulmonary Hypertension.

The role of electrocardiography (ECG) in chronic thromboembolic pulmonary hypertension (CTEPH) diagnosis and prognosticating has not been yet established. We aimed to assess the relationships of the recommended ECG criteria of right ventricular hypertrophy (RVH) with clot localization in CTEPH patients. ECG patterns of RVH according to the American College of Cardiology Foundation were assessed in patients with newly diagnosed CTEPH. We enrolled 58 (45.3%) patients with proximal and 70 (54.7%) with distal CTEPH. Receiver-operating characteristics curves analysis indicated that the following ECG abnormalities predicted proximal CTEPH localization: RV1 > 6 mm—AUC 0.75 (CI: 0.66–0.84, p < 0.00001); SV6 > 3 mm—AUC 0.70 (CI: 0.60–0.79, p < 0.00001); SI > RI wave—AUC 0.67 (CI: 0.58–0.77, p = 0.0004); RV1:SV1 > 1.0—AUC 0.66 (CI: 0.56–0.76, p = 0.0009); RV1 peak > 0.035 s (QRS < 120 ms)—AUC 0.66 (CI: 0.56–0.75, p = 0.0016); RV1:SV1 > RV3(V4):SV3(V4)—AUC-0.65 (CI: 0.54–0.75, p = 0.0081); RaVR > 4 mm—AUC 0.62 (CI: 0.52–0.71, p = 0.002) and PII > 2.5 mm—AUC 0.62 (CI: 0.52–0.72, p = 0.00162). Pulmonary vascular resistance significantly correlated with amplitudes of RV1 (r = 0.34, p = 0.008), SV6 (r = 0.53, p = 0.000027) and PII (r = 0.44, p = 0.00007). In patients with CTEPH, only 8 out of 23 ECG RVH criteria were useful for differentiating between proximal and distal CTEPH localization and we found that RV1 and SV6 may contribute as potential discriminators.

Optimizing the diagnosis and assessment of chronic thromboembolic pulmonary hypertension with advancing imaging modalities.

Imaging is key to nearly all aspects of chronic thromboembolic pulmonary hypertension including management for screening, assessing eligibility for pulmonary endarterectomy, and post-operative follow-up. While ventilation/perfusion scintigraphy, the gold standard technique for chronic thromboembolic pulmonary hypertension screening, can have excellent sensitivity, it can be confounded by other etiologies of pulmonary malperfusion, and does not provide structural information to guide operability assessment. Conventional computed tomography pulmonary angiography has high specificity, though findings of chronic thromboembolic pulmonary hypertension can be visually subtle and unrecognized. In addition, computed tomography pulmonary angiography can provide morphologic information to aid in pre-operative workup and assessment of other structural abnormalities. Advances in computed tomography imaging techniques, including dual-energy computed tomography and spectral-detector computed tomography, allow for improved sensitivity and specificity in detecting chronic thromboembolic pulmonary hypertension, comparable to that of ventilation/perfusion scans. Furthermore, these advanced computed tomography techniques, compared with conventional computed tomography, provide additional physiologic data from perfused blood volume maps and improved resolution to better visualize distal chronic thromboembolic pulmonary hypertension, an important consideration for balloon pulmonary angioplasty for inoperable patients. Electrocardiogram-synchronized techniques in electrocardiogram-gated computed tomography can also show further information regarding right ventricular function and structure. While the standard of care in the workup of chronic thromboembolic pulmonary hypertension includes a ventilation/perfusion scan, computed tomography pulmonary angiography, direct catheter angiography, echocardiogram, and coronary angiogram, in the future an electrocardiogram-gated dual-energy computed tomography angiography scan may enable a “one-stop” imaging study to guide diagnosis, operability assessment, and treatment decisions with less radiation exposure and cost than traditional chronic thromboembolic pulmonary hypertension imaging modalities.

The protective effects of radiofrequency pulmonary artery denervation on the progression of chronic thromboembolic pulmonary hypertension

Abstract This study aimed to assess the safety and efficacy of radiofrequency pulmonary artery denervation with the Simplicity system in patients with distal chronic thromboembolic pulmonary hypertension. Methods and results 60 chronic thromboembolic pulmonary hypertension patients with mean pulmonary artery pressure &amp;gt;25 mm Hg and absence of proximal artery lesion defined by pulmonary angiography were randomized into 2 groups. Group 1 included 30 patients who underwent pulmonary artery denervation procedure. The other 30 patients were assigned to the control group (only angio plus right heart catheterization). The procedure of pulmonary artery denervation was performed at the lateral wall of main pulmonary artery and ostium of the left and right pulmonary arteries using the electrode from Simplicity denervation system. The programmed ablation parameters were temperature &amp;gt;50°C and time = 120 s. Using the coronary guiding technique, the tip of electrode was applied at each spot rotating the tip with pace of 2 mm. The success was defined by decrease of mean pulmonary artery pressure &amp;gt;10%, absence of complications. The primary end point was comparison of mean pulmonary artery pressure change from baseline to 12 months in pulmonary artery denervation group compared with change from baseline to 12 months in control group. The secondary point was change in 6-min walk distance and pulmonary vascular resistance at the 12-month follow-up. There were no complications after pulmonary artery denervation. The hemodynamic success was achieved in 93% of all cases. The mean number of radiofrequency applications to achieve success was 10.3 per patient. During follow-up period 3 patients died in pulmonary artery denervation group: (1 died of gastro-intestinal bleeding, 2 – of right ventricular failure) and 3 patients in control group. The mean decreases in the mean pulmonary artery pressure were 8.7 mm Hg in the pulmonary artery denervation group and 3.1 mm Hg in control group (p&amp;lt;0.05). After pulmonary artery denervation in comparison with the control group was observed significant decrease in pulmonary vascular resistance (8.3±2.8 WU vs. 11.2±3.7). 6-min walk distance significantly increased by 81 m after pulmonary artery denervation and 29 m in control group (p&amp;lt;0.05). This improvement was associated with significant improvements in the WHO functional class. Conclusions The usage of the Simplicity denervation system in pulmonary artery denervation procedure is safe and effective. Further studies are required to determine the role of pulmonary artery denervation in the treatment of chronic thromboembolic pulmonary hypertension. The next step of pulmonary artery denervation development will be the use of this method combined with recommended treatment (medical therapy, pulmonary endarterectomy and balloon pulmonary angioplasty) as additional option, that may sufficiently improve outcomes in some patients Funding Acknowledgement Type of funding source: None

Klippel-Trenaunay syndrome as a rare cause of chronic thromboemboembolic pulmonary hypertension

Klippel-Trenaunay syndrome (KTS) is a congenital disorder characterized by cutaneous capillary malformations, soft tissue and bone hypertrophy, and multiple capillary, venous or lymphatic malformations. KTS is associated with recurrent thromboembolic events. We reported herein five cases of chronic thromboembolic pulmonary hypertension (CTEPH) associated with KTS (age minimum–maximum 26–50 years old, 3 males/2 females). Hemodynamics showed severe pulmonary hypertension (PH) with pulmonary vascular resistance ranging from 5.6 to 18.3 Wood units (WU), associated with marked clinical impairment (NYHA functional class III or IV in 4 patients). Computed tomography (CT) of the chest and pulmonary angiography confirmed proximal CTEPH accessible to surgical intervention in one patient and distal forms of CTEPH in 4 patients. Evolution after pulmonary endarterectomy showed hemodynamic normalization, while the patients with distal CTEPH had severe outcomes with 2 early deaths after PH diagnosis (44 and 35 months respectively). One patient with distal CTEPH was still alive 16 years after diagnosis on specific PH therapy and one was transplanted after 15 years because of right heart failure (death after 12 months). Histological analysis of the lung explants showed typical chronic thromboembolic material specific for CTEPH. In conclusion, KTS may be complicated by severe CTEPH requiring careful anticoagulation and multidisciplinary follow-up in expert centers to screen for disease potentially accessible to endarterectomy. In the modern management era of CTEPH, balloon pulmonary angioplasty will certainly be an interesting option in patients with inoperable disease.

Effect of domiciliary oxygen therapy on exercise capacity and quality of life in patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension: a randomised, placebo-controlled trial.

We investigated whether domiciliary oxygen therapy (DOXT) increases exercise capacity and quality of life in patients with pulmonary arterial or distal chronic thromboembolic pulmonary hypertension (PAH/CTEPH) presenting with mild resting hypoxaemia and exercise-induced oxygen desaturation. 30 patients with PAH/CTEPH, mean±sd age 60±15 years, pulmonary artery pressure 39±11 mmHg, resting arterial oxygen saturation measured by pulse oximetry (S pO2 ) ≥90%, S pO2 drop during a 6-min walk test ≥4%, on pulmonary hypertension-targeted medication, were randomised in a double-blind crossover protocol to DOXT and placebo (ambient air) treatment, each over 5 weeks, at 3 L·min-1 via nasal cannula overnight and when resting during the day. Treatment periods were separated by 2 weeks of washout. Co-primary outcomes were changes in 6-min walk distance (6MWD, breathing ambient air) and physical functioning scale of the 36-item short-form medical outcome questionnaire during treatment periods. DOXT increased the 6MWD from baseline 478±113 m by a mean (95% CI) of 19 (6-32) m, and physical functioning from 52±29 by 4 (0-8) points. Corresponding changes with placebo were 1 (-11-13) m in 6MWD and -2 (-6-2) points in physical functioning. Between-treatment differences in changes were 6MWD 18 (1-35) m (p=0.042) and physical functioning 6 (1-11) points (p=0.029). DOXT significantly improved the NewYork Heart Association functional class versus placebo. This first randomised trial in PAH/CTEPH patients with exercise-induced hypoxaemia demonstrates that DOXT improves exercise capacity, quality of life and functional class. The results support large long-term randomised trials of DOXT in PAH/CTEPH.

Real-Life Experience with Selexipag as an Add-On Therapy to Oral Combination Therapy in Patients with Pulmonary Arterial or Distal Chronic Thromboembolic Pulmonary Hypertension: A Retrospective Analysis.

Patients with pulmonary arterial hypertension (PAH) and distal chronic thromboembolic pulmonary hypertension (CTEPH) who still reveal risk factors of worse prognosis on double combination therapy may benefit from add-on therapy with the novel oral selective prostacyclin receptor agonist selexipag. We reviewed all patients with PAH/distal CTEPH in the Zurich cohort who received selexipag as add-on to oral combination therapy and retrieved New York Heart Association (NYHA) functional class, 6-min walk distance (6MWD), NT-pro-BNP, quality of life questionnaires (CAMPHOR and EuroQoL), tricuspid pressure gradient (TPG) by echocardiography and cardiopulmonary exercise test parameters (power output and oxygen uptake). Twenty-three patients with PAH/CTEPH (20/3), 14 females, median (quartiles) age 56 (46; 66) years received an oral triple therapy containing selexipag at a median dose of 2000 (1600; 3100) mcg during 221 (113; 359) days. The following parameters were stabilized from baseline to last FU: 6MWD (440 (420; 490) to 464 (420; 526)m), NYHA class (three to two), NT-pro-BNP (326 (167; 1725) to 568 (135; 1856) ng/l), TPG, power output, and oxygen uptake. Quality of life reflected by the CAMPHOR and EuroQoL improved. Early initiation of triple oral combination therapy including selexipag in PAH/CTEPH with intermediate risk factor profile may help to stabilize functional class, exercise performance, and pulmonary hemodynamics in a real-life setting and potentially improves quality of life. Whether these beneficial effects can be truly attributed to the addition of selexipag should be addressed in future randomized controlled trials.

Dead-space ventilation is linked to exercise capacity and survival in distal chronic thromboembolic pulmonary hypertension

Cardiopulmonary exercise testing (CPET) is frequently used for the evaluation of patients with pulmonary hypertension (PH). Non-operable distal chronic thromboembolic pulmonary hypertension (CTEPH) represents a unique subgroup of PH where microvascular disease resembling pulmonary arterial hypertension (PAH) may predominate and efficacious medical therapy is now available. However, little is known regarding the detailed CPET profile of patients with distal CTEPH, and whether ventilation and gas exchange responses are different from PAH. Forty-nine consecutive patients with non-operable distal CTEPH according to multidisciplinary team assessment and 45 PAH patients underwent CPET and right heart catheterization. Patients were followed up for a median of 3.2 years (interquartile range: 1.8 to 4.4). Pulmonary hemodynamics were similar in distal CTEPH and PAH groups, but patients with distal CTEPH achieved a lower percent predicted peak oxygen consumption (59 ± 13% vs 66 ± 14%, p < 0.05). At peak exercise, higher physiologic dead-space fraction (VD/VT) (0.45 ± 0.07 vs 0.35 ± 0.07, p < 0.0001) and higher arterial-to-end-tidal carbon dioxide gradient (9 ± 3 vs 5 ± 3 mm Hg, p < 0.0001) were observed in distal CTEPH compared with PAH. Ventilatory efficiency, expressed as VE/VCO2 slope, was also more impaired in distal CTEPH (52.2 ± 10.1 vs 43.8 ± 8.4 liters/min, p < 0.0001). In the distal CTEPH group only, higher VD/VT was associated with lower peak oxygen consumption (r = -0.46, p = 0.003) and worse survival. Compared with PAH, a distinct pattern of response to exercise was observed in distal CTEPH, characterized by increased dead-space ventilation that resulted in worse ventilatory efficiency and greater impairment of exercise capacity. In distal CTEPH, dead-space ventilation correlated with exercise capacity and was associated with survival.

Refined balloon pulmonary angioplasty driven by combined assessment of intra-arterial anatomy and physiology – Multimodal approach to treated lesions in patients with non-operable distal chronic thromboembolic pulmonary hypertension – Technique, safety and efficacy of 50 consecutive angioplasties

Background/ObjectivesBalloon pulmonary angioplasty (BPA) is an emerging therapeutic method in CTEPH. We aimed to prove the safety and efficacy of refined BPA driven by combined assessment of intra-arterial anatomy (IVUS/OCT) and physiology (pulmonary pressure ratio, PPR) in non-operable distal CTEPH. Methods11 pts (mean age 76, 59–84, 7 males) were enrolled in the BPA program according to the following inclusion criteria: 1. Non-operable CTEPH; 2. RHC with mPAP >30mmHg; 3. At least one segmental perfusion defect at lung scintigraphy; 4. WHO class>II. Overall, 9 pts underwent 27 BPA sessions (mean 3 sessions per patient, range 1–5), 50 pulmonary arteries were dilated (mean 6 vessels per patient, range 3–9; 2.03 dilated arteries per session). All the angioplasties were performed according to an algorithm, which incorporated anatomical and functional assessment of targeted lesions. ResultsWe performed BPA of 32 web lesions, 5 ring-like stenosis and 13 complete obstructions. BPA resulted in clinical and hemodynamic improvement. WHO class improved from pre-BPA to post-BPA (p=0.018), and 6 MWD increased from 304m to 384m (p=0.03), NT-proBNP dropped from 1248pg/ml to 730pg/ml (p<0.001). Mean PAP and PVR decreased (p=0.01), while CO and CI increased (p=0.01). All dilated arteries were patent at angiographic reassessment. No significant complications occurred and all treated patients are still alive. Insignificant transient reperfusion pulmonary oedema occurred in only 2 patients, who responded well to supplemental oxygen. ConclusionsRefined BPA with assessment of intrapulmonary physiology using a pressure wire and precise evaluation of anatomy with IVUS and OCT provides hemodynamic and functional improvement, with minimal complications in distal non-operable CTEPH. This observation requires further validation in a large prospective study.

TCT-26 Balloon Pulmonary Angioplasty Driven By Combined Assessment of Intra-Arterial Anatomy And Physiology In Patients With Non Operable Distal Chronic Thromboembolic Pulmonary Hypertension

Balloon pulmonary angioplasty (BPA) is an emerging therapeutic method in CTEPH. We aimed to prove the safety and efficacy of refined BPA driven by combined assessment of intra-arterial anatomy (IVUS/OCT) and physiology (pulmonary pressure ratio, PPR) in non-operable distal CTEPH. 11 pts (mean age

Refined balloon pulmonary angioplasty in inoperable chronic thromboembolic pulmonary hypertension — A multi-modality approach to the treated lesion

Introduction. Chronic thromboembolic pulmonary hypertension (CTEPH) represents uncommon or under-diagnosed sequel of acute or chronic pulmonary embolism (PE). The gold standard therapy for CTEPH is pulmonary endarterectomy (PEA) which markedly improves the prognosis or even cures the disease in the majority of patients with CTEPH [1]. Nevertheless some CTEPH patients are not operable due to small-vessel disease (“distal CTEPH”) due to significant co-morbidities making the risk of surgery unacceptably high [2,3].

Microvascular disease in chronic thromboembolic pulmonary hypertension: a role for pulmonary veins and systemic vasculature.

Limited numbers of operated patients with chronic thromboembolic pulmonary hypertension (CTEPH) are refractory to pulmonary endarterectomy (PEA) and experience persistent pulmonary hypertension (PH). We retrospectively assessed lung histology available from nine patients with persistent PH (ineffective PEA (inPEA) group) and from eight patients transplanted for distal CTEPH inaccessible by PEA (noPEA group). Microscopically observed peculiarities were compared with the histology of a recently developed CTEPH model in piglets. Pre-interventional clinical/haemodynamic data and medical history of patients from the inPEA and noPEA groups were collected and analysed. Conspicuous remodelling of small pulmonary arteries/arterioles, septal veins and pre-septal venules, including focal capillary haemangiomatosis, as well as pronounced hypertrophy and enlargement of bronchial systemic vessels, were the predominant pattern in histology from both groups. Most findings were reproduced in our porcine CTEPH model. Ink injection experiments unmasked abundant venular involvement in so-called small vessel or microvascular disease, as well as post-capillary bronchopulmonary shunting in human and experimental CTEPH. Microvascular disease is partly due to post-capillary remodelling in human and experimental CTEPH and appears to be related to bronchial-to-pulmonary venous shunting. Further studies are needed to clinically assess the functional importance of this finding.

Pulmonary endarterectomy for distal chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension can be cured by pulmonary endarterectomy. Operability assessment remains a major concern, because there are no well-defined criteria to discriminate proximal from distal obstructions, and surgical candidacy depends mostly on the surgeon's experience. The intraoperative classification of chronic thromboembolic pulmonary hypertension describes 4 types of lesions, based on anatomy and location. We describe our recent experience with the more distal (type 3) disease. More than 500 pulmonary endarterectomies were performed at Foundation I.R.C.C.S. Policlinico San Matteo (Pavia, Italy). Because of recent changes in the patient population, 331 endarterectomies performed from January 2008 to December 2013 were analyzed. Two groups of patients were identified according to the intraoperative classification: proximal (type 1 and type 2 lesions, 221 patients) and distal (type 3 lesions, 110 patients). The number of endarterectomies for distal chronic thromboembolic pulmonary hypertension increased significantly over time (currently ∼37%). Deep venous thrombosis was confirmed as a risk factor for proximal disease, whereas patients with distal obstruction had a higher prevalence of indwelling intravascular devices. Overall hospital mortality was 6.9%, with no difference in the 2 groups. Postoperative survival was excellent. In all patients, surgery was followed by a significant and sustained improvement in hemodynamic, echocardiographic, and functional parameters, with no difference between proximal and distal cases. Although distal chronic thromboembolic pulmonary hypertension represents the most challenging situation, the postoperative outcomes of both proximal and distal cases are excellent. The diagnosis of inoperable chronic thromboembolic pulmonary hypertension should be achieved only in experienced centers, because many patients who have been deemed inoperable might benefit from favorable surgical outcomes.