Residual Pulmonary Hypertension Research Articles

Consensus on the procedure of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is classified as group IV pulmonary hypertension, characterized by thrombotic occlusion of the pulmonary arteries leading to vascular stenosis or obstruction, progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, and eventual right heart failure. Unlike other types of pulmonary hypertension, the prognosis of CTEPH can be significantly improved by surgery, vascular intervention, and/or targeted drug therapy. Pulmonary endarterectomy (PEA) is the preferred treatment of choice for CTEPH. However, PEA is an invasive procedure with high operative risks, and is currently only performed in a few centers in China. Balloon pulmonary angioplasty (BPA) is an emerging interventional technique for CTEPH, serving as an alternative for patients who are ineligible for PEA or with residual pulmonary hypertension after PEA. BPA is gaining traction in China, but its widespread adoption is limited due to its complexity, operator skills, and equipment requirements, a lack of standard operating procedures and technical guidance, which limit the further improvement and development of BPA in China. To address this, a multidisciplinary panel of experts was convened to develop the Consensus on the Procedure of Balloon Pulmonary Angioplasty for the Chronic Thromboembolic Pulmonary Hypertension, which fomulates guidelines on BPA procedural qualification, perioperative management, procedural planning, technical approach, and complication prevention, with the aim of providing recommendations and clinical guidance for BPA treatment in CTEPH and standardizing its clinical application in this setting. Summary of recommendations: Recommendation 1: It is recommended that physicians who specialize in pulmonary vascular diseases take the lead in formulating the diagnostic and treatment plans for CTEPH, using a multidisciplinary approach.Recommendation 2: Training in BPA technique is critical; novice operators should undergo standardized operative training with at least 50 procedures under the guidance of experienced physicians before embarking on independent BPA procedures.Recommendation 3: BPA requires catheterization labs, angiography systems, standard vascular interventional devices and consumables, drugs, and emergency equipment.Recommendation 4: Patient selection for BPA should consider cardiac and pulmonary function, coagulation status, and comorbid conditions to determine indications and contraindications, thereby optimizing the timing of the procedure and improving safety.Recommendation 5: In experienced centers, patients deemed likely to benefit from early BPA, based on clinical and imaging features of CTEPH and without elevated D-dimer levels, could bypass standard 3-month anticoagulation therapy.Recommendation 6: BPA is a complex interventional treatment that requires thorough pre-operative assessment and preparation.Recommendation 7: The use of perioperative anticoagulants in BPA requires a comprehensive risk assessment of intraoperative bleeding by the operator for individualized decision making.Recommendation 8: A variety of venous access routes are available for BPA; unless contraindicated, the right femoral vein is usually preferred because of its procedural convenience and reduced radiation exposure.Recommendation 9: For the different types of vascular lesion in CTEPH, treatment of ring-like stenoses, web-like lesions, and subtotal occlusions should be prioritized before addressing complete occlusions and tortuous lesions, in order to reduce complications and improve procedural safety.Recommendation 10: A targeted, incremental balloon dilatation strategy based on vascular lesions is recommended for BPA.Recommendation 11: Intravascular pulmonary artery imaging technologies, such as OCT and IVUS can assist in accurate vessel sizing and confirmation of wire placement in the true vascular lumen. Pressure wires can be used to objectively assess the efficacy of dilatation during BPA.Recommendation 12: Endpoints for BPA treatment should be individually assessed, taking into account improvements in clinical symptoms, hemodynamics, exercise tolerance, and quality of life.Recommendation 13: Post-BPA routine monitoring of vital signs is essential; anticoagulation therapy should be initiated promptly post-procedure in the absence of complications. In cases of intraoperative hemoptysis, postoperative anticoagulation regimen adjustments should be adjusted according to the bleeding severity.Recommendation 14: If reperfusion pulmonary edema occurs during or after BPA, ensure adequate oxygenation, diuresis, and consider non-invasive positive-pressure ventilation if necessary, while severe cases may require early mechanical ventilation assistance or ECMO.Recommendation 15: In cases of intraoperative hemoptysis, temporary balloon occlusion to stop bleeding is recommended, along with protamine to neutralize heparin. Persistent bleeding may warrant the use of gelatin sponges, coil embolization, or covered stent implantation.Recommendation 16: For contrast imaging during BPA, non-ionic, low or iso-osmolar contrast agents are recommended, with hydration status determined by the patient's clinical condition, cardiac and renal function, and intraoperative contrast volume used.

Operative Repair of Aortopulmonary Window: A 25-Year Experience.

Background: Aortopulmonary window (APW) is a rare anomaly with variable morphology and associated cardiac anomalies. We evaluated impact of patient and operative factors on mid-term outcomes following APW repair. Methods: Twenty-nine patients underwent surgical APW repair at our institution from 1996 to 2022. Eight (28%) had simple APW, accompanied by only atrial septal defect or patent ductus arteriosus; 21 (72%) had complex APW with additional cardiovascular lesions, including nine with interrupted aortic arch. Median operative age was 19 days (range 2 days-1.5 years) via single-patch (n = 12, 41%), double-patch (n = 15, 52%), or ligation and division (n = 2, 7%). Results: The only mortality occurred in-hospital 1.4 years postoperatively following remote myocardial infarction. Factors associated with longer postoperative length of stay were complex APW (P = .003), genetic syndrome (P = .003), noncardiovascular comorbidities (P = .002), lower birth weight (P = .03), and lower operative weight (P = .03). Six patients (21%) with complex APW underwent unplanned cardiothoracic reintervention(s), including two with arch reintervention following arch advancement for interruption. Reintervention-free survival was similar for simple versus complex APW, operative age categories, and repair techniques. At median follow-up 5.5 years postoperatively, no patients had residual APW or persistent pulmonary hypertension, 1 (3%) had greater than mild ventricular dysfunction, and 25 (89% survivors) had NYHA class I functional status. Conclusions: Operative APW repair has excellent mid-term survival, durability, and functional status, regardless of operative age, cardiovascular comorbidities, or repair technique. Cardiac and noncardiac comorbidities may be associated with prolonged length of stay.

NT-pro-BNP is predictive of morbidity and mortality after pulmonary thromboendarterectomy and is independent of preoperative hemodynamics.

Current predictors of clinical outcomes after pulmonary thromboendarterectomy (PTE) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) are largely limited to preoperative clinical characteristics. N-terminal-pro-brain natriuretic peptide(NT-pro-BNP), a biomarker of right ventricular dysfunction, has not yet been well described as one such predictor. From 2017 to 2021, 816 patients with CTEPH referred to the University of California, San Diego for PTE were reviewed for differences in NT-pro-BNP to predict preoperative characteristics and postoperative outcomes up to 30 days post-PTE. For analysis, NT-pro-BNP was dichotomized to less than/equal to or greater than 1000 pg/mL based on the mean of the study population. Mean NT-pro-BNP was 1095.9 ±1783.4 pg/mL and median was 402.5 pg/mL (interquartile range: 119.5-1410.8). Of the 816 patients included, 250 had NT-pro-BNP > 1000 pg/mL. Those with NT-pro-BNP > 1000 pg/mL were significantly more likely to have worse preoperative functional class (III-IV) and worse preoperative hemodynamics. Patients with NT-pro-BNP > 1000 pg/mL also tended to have more postoperative complications including reperfusion pulmonary edema (22% vs. 5.1%, p < 0.001), airway hemorrhage (8.4% vs. 4.9%, p = 0.075), residual pulmonary hypertension (11.9% vs. 3.1%, p < 0.001), and 30-day mortality (4.8% vs. 1.1%, p = 0.001). Even after adjusting for confounders, patients with NT-pro-BNP > 1000 pg/mL had a 2.48 times higher odds (95% confidence interval: 1.45-4.00) of reaching a combined endpoint that included the above complications. Preoperative NT-pro-BNP > 1000 pg/mL is a strong predictor of more severe preoperative hemodynamics and identifies patients at higher risk for postoperative complications.

Status and Future Directions for Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Disease With and Without Pulmonary Hypertension: A Scientific Statement From the American Heart Association.

Balloon pulmonary angioplasty continues to gain traction as a treatment option for patients with chronic thromboembolic pulmonary disease with and without pulmonary hypertension. Recent European Society of Cardiology guidelines on pulmonary hypertension now give balloon pulmonary angioplasty a Class 1 recommendation for inoperable and residual chronic thromboembolic pulmonary hypertension. Not surprisingly, chronic thromboembolic pulmonary hypertension centers are rapidly initiating balloon pulmonary angioplasty programs. However, we need a comprehensive, expert consensus document outlining critical concepts, including identifying necessary personnel and expertise, criteria for patient selection, and a standardized approach to preprocedural planning and establishing criteria for evaluating procedural efficacy and safety. Given this lack of standards, the balloon pulmonary angioplasty skill set is learned through peer-to-peer contact and training. This document is a state-of-the-art, comprehensive statement from key thought leaders to address this gap in the current clinical practice of balloon pulmonary angioplasty. We summarize the current status of the procedure and provide a consensus opinion on the role of balloon pulmonary angioplasty in the overall care of patients with chronic thromboembolic pulmonary disease with and without pulmonary hypertension. We also identify knowledge gaps, provide guidance for new centers interested in initiating balloon pulmonary angioplasty programs, and highlight future directions and research needs for this emerging therapy.

Evaluating the efficacy of balloon pulmonary angioplasty using quantitative analysis of SPECT pulmonary ventilation/perfusion scintigraphy in patients with chronic thromboembolic pulmonary hypertension.

Single-photon emission computed tomography (SPECT) ventilation perfusion imaging is the main imaging method for the diagnosis of pulmonary embolism, and its application in the diagnosis and efficacy evaluation of chronic thromboembolic pulmonary hypertension (CTEPH) has been paid more and more attention. In recent years, with the development of computer software technology, ventilation/perfusion (V/Q) imaging quantitative analysis technology has become more and more mature. The objective of this study was to investigate the utility of quantitative analysis of pulmonary V/Q scintigraphy in evaluating the efficacy of balloon pulmonary angioplasty (BPA) in patients with CTEPH. In this retrospective analysis, we collected data of patients diagnosed with CTEPH who underwent BPA at the China-Japan Friendship Hospital from April 2018 to September 2020. The sample consisted of 23 males and 28 females, with an average age of 55.1±12.7 years. All patients underwent V/Q scintigraphy within one week before surgery, and we reviewed the pulmonary angiography within 1-3 months following the last BPA procedure. We repeated V/Q scintigraphy within 1 week before or after the pulmonary angiography, at the time of collecting clinical and hemodynamic parameters of these patients. We divided the patients into two groups based on the presence of residual pulmonary hypertension post-surgery and compared the pre- and post-operative quantitative pulmonary perfusion defect percentage scores (PPDs%) using the t-test. In all, 102 V/Q scintigraphy scans were performed in 51 patients. The quantitative PPDs% were positively correlated with the hemodynamic indexes mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and mean right ventricular pressure (RVP) (r=0.605, 0.391, and 0.464, respectively, all P<0.001) and negatively correlated with the 6-minute walking distance (6MWD) (r=-0.254, P=0.010). The average preoperative quantitative PPDs% were (49.0±15.6)% which significantly decreased to (33.5±13.9)% after surgery (t=11.249, P<0.001). The preoperative quantitative PPDs% were (54.7±15.7)% and (44.0±13.8)% in the residual pulmonary hypertension group and the non-residual pulmonary hypertension group, respectively (t=2.599, P=0.012). The postoperative quantitative PPDs% were (41.5±12.5)% and (26.3±11.0)%, in the residual pulmonary hypertension group and the non-residual pulmonary hypertension group, respectively (t=4.647, P<0.001). In this study, we found that quantitative analysis of SPECT pulmonary V/Q scintigraphy adequately reflected the pulmonary artery pressure and clinical status in patients with CTEPH. Our results demonstrate its definite utility in predicting residual pulmonary hypertension and in evaluating the postoperative efficacy of BPA in patients with CTEPH.

Recurrent pulmonary hypertension after balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension

Balloon pulmonary angioplasty improves the hemodynamics of patients with inoperable chronic thromboembolic pulmonary hypertension; however, the clinical impact of recurrent pulmonary hypertension after balloon pulmonary angioplasty remains unclear. We retrospectively reviewed 262 consecutive patients with chronic thromboembolic pulmonary hypertension who underwent balloon pulmonary angioplasty between July 2009 and December 2020; 158 (65±12years; males, 20%; median follow-up period, 45 [26, 66]months) with follow-up right heart catheterization and no residual pulmonary hypertension were included. Recurrent pulmonary hypertension was defined as mean pulmonary arterial pressure <25mm Hg at the first evaluation after balloon pulmonary angioplasty and ≥25mm Hg at follow-up evaluation requiring additional treatment with balloon pulmonary angioplasty or pulmonary vasodilators. Recurrent pulmonary hypertension was observed in 11 patients; the state occupation probability of recurrence at 5years was 9.0% (95% confidence interval: 5.0%-18.9%). Only 1 case (0.6%) of recurrent pulmonary hypertension showed vascular restenosis and reocclusion of previously treated lesions, with more significant hemodynamic and exercise capacity deterioration than the other cases. Additional treatments for recurrent pulmonary hypertension (balloon pulmonary angioplasty in 9 patients, pulmonary vasodilators in 4 patients) improved the mean pulmonary arterial pressure from 27 [26, 29] to 22 [19, 23] mm Hg (p<0.01). Recurrence had a low probability of transitioning to death in an illness-death model. No specific risk factors for recurrent pulmonary hypertension were identified. Symptomatic recurrent pulmonary hypertension due to vascular restenosis or reocclusion after balloon pulmonary angioplasty was extremely rare. Most cases of recurrent pulmonary hypertension were mild, did not worsen clinically, and had favorable prognoses.

Long-term effects of pulmonary endarterectomy on pulmonary hemodynamics, cardiac function, and exercise capacity in chronic thromboembolic pulmonary hypertension

Long-term changes in exercise capacity and cardiopulmonary hemodynamics after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) have been poorly described. We analyzed the data from 2 prospective surgical CTEPH cohorts in Hammersmith Hospital, London, and Amsterdam UMC. A structured multimodal follow-up was adopted, consisting of right heart catheterization, cardiac magnetic resonance imaging, and cardiopulmonary exercise testing before and after PEA. Preoperative predictors of residual pulmonary hypertension (PH; mean pulmonary artery pressure >20mm Hg and pulmonary vascular resistance ≥2WU) and long-term exercise intolerance (VO2max <80%) at 18months were analyzed. A total of 118 patients (61 from London and 57 from Amsterdam) were included in the analysis. Both cohorts displayed a significant improvement of pulmonary hemodynamics, right ventricular (RV) function, and exercise capacity 6months after PEA. Between 6 and 18months after PEA, there were no further improvements in hemodynamics and RV function, but the proportion of patients with impaired exercise capacity was high and slightly increased over time (52%-59% from 6 to 18months). Long-term exercise intolerance was common and associated with preoperative diffusion capacity for carbon monoxide (DLCO), preoperative mixed venous oxygen saturation, and postoperative PH and right ventricular ejection fraction (RVEF). Clinically significant RV deterioration (RVEF decline >3%; 5 [9%] of 57 patients) and recurrent PH (5 [14%] of 36 patients) rarely occurred beyond 6months after PEA. Age and preoperative DLCO were predictors of residual PH post-PEA. Restoration in exercise tolerance, cardiopulmonary hemodynamics, and RV function occurs within 6months. No substantial changes occurred between 6 and 18months after PEA in the Amsterdam cohort. Nevertheless, long-term exercise intolerance is common and associated with postoperative RV function.

Dynamics of social and labor status in patients undergoing pulmonary thromboendarterectomy

Aim. To study the dynamics of social and labor status in patients with chronic thromboembolic pulmonary hypertension (CTEPH) 6 months after pulmonary endarterectomy (PEA) and to identify clinical factors affecting the resumption of labor activity in the late postoperative period.Material and methods. The study included 79 patients with CTEPH scheduled for PEA. The average age was 48.6 (39.3-59.4) years. We analyzed clinical and functional data, as well as social and labor status before and 6 months after PEA. Using multivariate regression analysis, the factors influencing the resumption of labor activity after PEA, were studied.Results. In the general cohort of patients with CTEPH, 6 months after surgery, a slight increase in the proportion of working patients of all ages was revealed - from 55.7% to 65.8% (p=0.19). In the subgroup of patients of working age (61 people), the proportion of working patients in dynamics increased significantly – from 67.2 to 85.2% (p=0.03). Multivariate regression analysis showed a protective effect of the 2nd stage of rehabilitation on social and labor status after PEA – OR 4.2 (2.9-8.3 95%CI) (p=0.01). The presence of atrial fibrillation and residual pulmonary hypertension negatively affected the resumption of labor activity in the long-term period after PEA – OR 0.6 (0.3-0.9 95%CI) (p = 0.03) and OR 0.7 (0.2-0.8 95%CI) (p=0.01) respectively.Conclusion. The dynamics of the social and labor status of patients with CTEPH 6 months after PEA is characterized by a significant increase in the proportion of working patients of working age from 67.2 to 85.2% compared with the preoperative level. The leading protective factor for the renewal of labor potential in patients with CTEPH within 6 months after PEE is the underwenting of the 2nd stage of rehabilitation. Residual pulmonary hypertension and atrial fibrillation are limiting factors for resuming of labor activity.

Multiparametric assessment of right ventricular function in heart transplant recipients by echocardiography and relations with pulmonary hemodynamics

AbstractObjectiveRight ventricular (RV) dilatation and dysfunction are usually present in heart transplant (HTx) patients and worsened with residual pulmonary hypertension (PH). We aimed to determine the ability of different echocardiographic modalities to evaluate RV function in comparison with cardiac magnetic resonance (CMR) and their relations with pulmonary hemodynamics in HTx patients.MethodsA total of 62 data sets [echocardiographic, hemodynamic, and CMR] were acquired from 35 HTx patients. Comprehensive echocardiography, including two‐dimensional (2D) transthoracic echocardiography, speckle tracking echocardiography, and three‐dimensional (3D) echocardiography, was performed. Mean pulmonary artery pressure (mPAP) was obtained invasively from right heart catheterization. The correlations between all echocardiographic parameters and CMR imaging data and the differences between patients with and without residual PH were evaluated.ResultsDiastolic and systolic RV volumes and RV ejection fraction (RVEF) by 3D echocardiography correlated strongly with CMR‐derived volumes and RVEF (r = .91, r = .79, r = .64; p &lt; .0001 for each, respectively). Among other parameters, RV fractional area change (r = .439; p &lt; .001) and RV free wall longitudinal strain (RVFW‐LS) (r = −.34; p &lt; .05) correlated moderately with CMR‐RVEF, whereas tricuspid annulus S’ velocity (r = .29; p &lt; .05) and tricuspid annular systolic plane excursion (r = .27; p &lt; .05) correlated weakly with CMR‐RVEF. Additionally, 3D‐RVEF and RVFW‐LS were significantly decreased in studies with mPAP ≥ 20 mm Hg in comparison to those with mPAP &lt; 20 mm Hg (47.7 ± 3.7 vs. 50.9 ± 5.3, p = .04 and −15.5 ± 3.1 vs. −17.5 ± 3, p = .03, respectively).ConclusionThe best method for the evaluation of RV function in HTx recipients is 3D echocardiography. Besides, the subclinical impact of residual PH on RV function can be best determined by RVFW‐LS and 3D‐RVEF in these patients.

Clinical impact of residual pulmonary hypertension based on revised criteria after balloon pulmonary angioplasty

Abstract Background Balloon pulmonary angioplasty (BPA) improves haemodynamics, exercise capacity, and prognosis in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, the treatment goal of BPA is not well established. The European Society of Cardiology guidelines published in 2022 revised the diagnosis of pulmonary hypertension from resting mean pulmonary arterial pressure (mPAP) ≥25 mmHg to mPAP &amp;gt;20 mmHg because mild elevation of pulmonary hypertension has decreased exercise capacity and worsened the prognosis. The clinical impact of normalization in resting pulmonary hypertension after balloon pulmonary angioplasty is not investigated. Purpose The purpose of this study is to clarify the clinical impact of mPAP normalization after BPA as a treatment goal in patients with CTEPH. Methods We retrospectively reviewed consecutive 236 CTEPH patients (68 [55,75] yrs., Male 52 (22%)) who completed BPA procedures from July 2009 to December 2020 and had haemodynamics evaluation after the procedures and had mPAP &amp;lt;30 mm Hg after BPA. We extracted two groups with mPAP &amp;lt;20 mmHg (Non-PH group) and 21≤ mPAP &amp;lt;30 mmHg (Residual-PH group) after BPA. Results The median follow-up period from the final BPA session was 38 [22,61] months. In both the Non-PH and Residual-PH groups, BPA significantly improved mPAP (37 [29,43] to 18 [16,19] mmHg, P&amp;lt;0.01 and 38 [34,45] to 23 [22,26], P&amp;lt;0.01, respectively) and cardiac index (CI) (2.15 [1.86,2.63] to 2.39 [2.11,2.80] L/min/m2, P&amp;lt;0.01 and 2.25 [1.87,2.63] to 2.50 [2.23,2.88] L/min/m2, P&amp;lt;0.01, respectively). There were no significant differences in CI after BPA between the Non-PH and Residual-PH groups. The 6-minute walk distance (6MWD) after BPA was shorter in the Residual-PH group than in the Non-PH group (435m and 480m, P&amp;lt;0.01). However, the estimated 5-year survival in the Non-PH and Residual-PH groups was comparable (96.3% and 99.1%, P=0.23, Figure 1). Patients in the Residual-PH group showed significantly shorter 6MWD and higher mPAP before BPA, and required more procedures (P&amp;lt;0.01, 0.02, 0.03, respectively). Additional multivariate logistic regression analysis revealed that shorter 6MWD before BPA was a significant predictor of residual PH (odds ratio=1.03, P=0.04). Conclusions The Residual-PH group had lower exercise capacity than the Non-PH group, although the prognosis in the Residual-PH group was similar to that in the Non-PH group.Figure 1

Abstract 13665: Clinical Outcomes and Predictors of Residual Pulmonary Hypertension in Patients Undergoing Transcatheter Aortic Valve Replacement

Background: Although transcatheter aortic valve replacement (TAVR) improves pulmonary hypertension (PH) secondary to aortic stenosis (AS), PH can remain after TAVR. We sought to investigate the outcomes and predictors of residual PH after TAVR. Methods: A total of 491 consecutive patients underwent TAVR between 2014 and 2023 at our institution. After excluding patients without baseline or postoperative transthoracic echocardiography, we stratified 483 patients according to baseline and postprocedural PH estimated by systolic pulmonary artery pressure &gt;36 mmHg as follows: no PH group (n=285), improved PH group (n=87), residual PH group (n=111). Outcome measures were the composite of cardiac death and heart failure (HF) hospitalization. Logistic regression analysis was used to identify the predictors of residual PH. Variables included in the model were age, atrial fibrillation (AF), left ventricular ejection fraction, left atrial dilatation, moderate/severe mitral regurgitation, moderate/severe tricuspid regurgitation (TR). Results: The mean age was 83.6±5.4 years, and 314 (65%) were female. Patients in residual PH group were more likely to have AF, higher left atrial volume index, moderate/severe MR, and moderate/severe TR, compared with patients in no PH group. Compared with no PH group, the cumulative incidence of the composite of cardiac death and HF hospitalization were comparable in improved PH group (6.1% vs. 10.5 at 2 years, P=0.3), but significantly higher in residual PH group (6.1% vs. 20.6% at 2 years, P=0.002) (Figure). Multivariable logistic regression analysis showed that AF (Odds ratio [OR] 1.91, 95% confidence interval [CI] 1.09-3.32), moderate/severe TR (OR 4.09, 95% CI 2.30-7.28) were independently associated with residual PH. Conclusions: Among patients undergoing TAVR, residual PH were associated with increased risk of adverse cardiac events. AF, moderate or severe TR were independent predictors of residual PH after TAVR.

Chronic thromboembolic pulmonary hypertension: epidemiology, diagnosis, treatment — current state of the problem

Chronic thromboembolic pulmonary hypertension is group IV of pulmonary hypertension, which develops with occlusive-stenotic lesions of the pulmonary artery after a pulmonary embolism. There are no clear data on the epidemiology of this disease. At the same time, it is obvious that it is much more widespread than is commonly believed. This is due to the nonspecific clinical picture and the lack of awareness of clinicians about this disease. On the one hand, the pathogenesis of CTEPH is well studied and in many respects similar to pulmonary arterial hypertension, on the other hand, it is not clear why blood clots do not dissolve in a certain percentage of patients. Diagnosis of chronic thromboembolic pulmonary hypertension is fairly well described and should be carried out according to a special algorithm. The treatment of choice is pulmonary endarterectomy. In inoperable patients and patients with residual pulmonary hypertension after surgery, it is possible to perform balloon angioplasty of the pulmonary artery and PAH-specific therapy. In our study, the safety and efficacy of a new method for the treatment of a residual form of chronic thromboembolic pulmonary hypertension, radiofrequency denervation of the pulmonary artery, has been proven. The pathogenetic basis of this technique is the desympathization of the pulmonary circulation by radiofrequency destruction of the autonomic ganglia of the bifurcation of the pulmonary artery and the interruption of the so-called pulmo-pulmonary reflex.

Perioperative extracorporeal membrane oxygenation support for pulmonary endarterectomy: A 17-year experience from the UK national cohort

Pulmonary endarterectomy(PEA) is the guideline recommended treatment for patients with chronic thromboembolic pulmonary hypertension(CTEPH). However, some patients develop severe cardiopulmonary compromise either prior to surgery, intraoperatively or early postoperatively. This may result from advanced CTEPH, reperfusion pulmonary oedema, massive endobronchial bleeding or right ventricular(RV) failure secondary to residual pulmonary hypertension. Conventional cardiorespiratory support is ineffective when these complications are severe. Since 2005 we used extracorporeal membrane oxygenation(ECMO) as a rescue therapy for this group. We review our experience with ECMO support in these patients. Retrospective analysis of patients who received perioperative ECMO for PEA from a single national centre from August 2005 to July 2022. Data was prospectively collected. One hundred and ten patients (4.7%) had extreme cardiorespiratory compromise requiring perioperative ECMO. Nine were established on ECMO before PEA. Of those who received ECMO postoperatively, thirty-nine were for refractory reperfusion lung injury, twenty for RV failure, thirty-one for endobronchial bleeding and the remaining eleven were for 'other' reasons such as cardiopulmonary resuscitation following late tamponade and aspiration pneumonitis. 62 (56.4%) were successfully weaned from ECMO. 57 patients left the hospital alive giving a salvage rate of 51.8%. High BMI was identified as an independent risk factor for worse outcome for patients needing ECMO for reperfusion lung injury(p<0.001). Distal disease(Jamieson Type III) and significant residual pulmonary hypertension were also predictors of mortality on ECMO support. Overall 5 and 10-year survival in patients who were discharged alive following ECMO support was 73.9% (SE: 6.1%) and 58.2% (SE: 9.5%), respectively. Perioperative ECMO support has an appropriate role as rescue therapy for this group. Over 50% survived to hospital discharge. These patients had satisfactory longer-term survival.

Pulmonary endarterectomy in patients with occlusive isolated pulmonary vasculitis

BackgroundIsolated pulmonary vasculitis (IPV) is a rare, insidious, and localized inflammatory disease affecting the pulmonary arteries, often leading to severe luminal obstruction. The prognosis for patients with occlusive IPV is poor, and there is currently a lack of effective treatments. The objective of this study was to evaluate the performance of pulmonary endarterectomy (PEA) as a treatment for occlusive IPV.MethodsThis single-center retrospective analysis included patients who received PEA for occlusive IPV between January 2018 and June 2022. Clinical characteristics and hemodynamic parameters were evaluated at baseline and follow-up.ResultsAmong 114 consecutive patients who underwent PEA, occlusive IPV was identified in 7 patients. Two patients underwent bilateral PEA for the involvement of both pulmonary arteries. Patch angioplasty was performed to treat four severe constrictions. One patient died from residual pulmonary hypertension after limited PEA of a transmural vascular lesion. In addition, no obvious surgical complications were observed. Three months after PEA, a substantial relief in symptoms was achieved. Also, there is a decrease in the mean pulmonary artery pressure (median 33 [20–48] mmHg before versus median 21 [16–26] mmHg after; P < 0.018) and pulmonary arterial resistance (median 234 [131–843] dyn.s.cm−5 versus median 180 [150–372] dyn.s.cm−5; P = 0.310). Three patients experienced a relapse of restenosis of the treated arteries within a 6-month follow-up period, despite daily oral prednisolone administration. They were treated with balloon pulmonary angioplasty of both the main pulmonary arteries and branches.ConclusionsPEA is a valuable choice for treating occlusive IPV, with notable hemodynamic and clinical advantages. To increase long-term vascular patency, complete management should be optimized.

Residual pulmonary hypertension after left to right shunt closure in common pediatric congenital heart diseases: rate and risk factors

Introduction: Left to right shunt in congenital heart disease is the common causes of pulmonary hypertension (PH) in children, and the pulmonary pressure sometime isn’t recovered to normal value after the shunts closed. Residual PH after correcting these shunts may cause deaths. The purpose of this study was to describe the rate of residual PH after surgical closure the left to right shunts in pediatric congenital heart disease and determine its risk factors.&#x0D; Patients and methods: A retrospective study was performed on the medical recorded documents of 59 children who were diagnosed pulmonary artery hypertension associated with common left to right shunt congenital heart diseases and performed shunt closure surgically at Cho Ray hospital between January 2020 and May 2022. Systolic pulmonary artery pressure (PAPs) was measured via tricuspid regurgitation jet on transthoracic echocardiography (mode: continuous wave doppler, plane: apical 4-chamber). PH was defined as PAPs ≥ 40mmHg. Postoperative PAPs was measured 1 day before discharge.&#x0D; Results: The median age and weight at surgery were 7 months (2 – 215) and 5.9 kg (3.6 – 35), 59.3% was female. Preoperatively, 66.1% were mild PH, 33.9% moderate. Postoperatively, 10 patients (17%) diagnosed residual PH and all was mild. Among 10 patients with residual PH: 7 were combined defects (5 VSD-PDA, 2 VSD-ASD), 3 simple defects (2 VSD, 1 ASD). Preoperative high pulmonary pressure was associated with residual PH (correlation coefficient 0.116, p = 0.001). Conclusions: The proportion of patients with postoperatiovely residual PH is significant and most of these cases are combined shunt. Preoperative high pulmonary pressure is related to residual PH.

Perioperative Management in Pulmonary Endarterectomy.

Pulmonary endarterectomy (PEA) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension (PH), provided lesions are proximal enough in the pulmonary vasculature to be surgically accessible and the patient is well enough to benefit from the operation in the longer term. It is a major cardiothoracic operation, requiring specialized techniques and instruments developed over several decades to access and dissect out the intra-arterial fibrotic material. While in-hospital operative mortality is low (<5%), particularly in high-volume centers, careful perioperative management in the operating theater and intensive care is mandatory to balance ventricular performance, fluid balance, ventilation, and coagulation to avoid or treat complications. Reperfusion pulmonary edema, airway hemorrhage, and right ventricular failure are the most problematic complications, often requiring the use of extracorporeal membrane oxygenation to bridge to recovery. Successful PEA has been shown to improve both morbidity and mortality in large registries, with survival >70% at 10 years. For patients not suitable for PEA or with residual PH after PEA, balloon pulmonary angioplasty and/or PH medical therapy may prove beneficial. Here, we describe the indications for PEA, specific surgical and perioperative strategies, postoperative monitoring and management, and approaches for managing residual PH in the long term.

How Would I Treat My Own Chronic Thromboembolic Pulmonary Hypertension in the Perioperative Period?

Chronic thromboembolic pulmonary hypertension (CTEPH) results from an incomplete resolution of acute pulmonary embolism, leading to occlusive organized thrombi, vascular remodeling, and associated microvasculopathy with pulmonary hypertension (PH). A definitive CTEPH diagnosis requires PH confirmation by right-heart catheterization and evidence of chronic thromboembolic pulmonary disease on imaging studies. Surgical removal of the organized fibrotic material by pulmonary endarterectomy (PEA) under deep hypothermic circulatory arrest represents the treatment of choice. One-third of patients with CTEPH are not deemed suitable for surgical treatment, and medical therapy or interventional balloon pulmonary angioplasty presents alternative treatment options. Pulmonary endarterectomy in patients with technically operable disease significantly improves symptoms, functional capacity, hemodynamics, and quality of life. Perioperative mortality is <2.5% in expert centers where a CTEPH multidisciplinary team optimizes patient selection and ensures the best preoperative optimization according to individualized risk assessment. Despite adequate pulmonary artery clearance, patients might be prone to perioperative complications, such as right ventricular maladaptation, airway bleeding, or pulmonary reperfusion injury. These complications can be treated conventionally, but extracorporeal membrane oxygenation has been included in their management recently. Patients with residual PH post-PEA should be considered for medical or percutaneous interventional therapy.

Impact of sex on outcome after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension

The impact of sex on long-term outcomes after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (PH) remains unclear. We therefore examined the early and long-term outcome after PEA to determine whether sex had an impact on the risk of residual PH and need for targeted PH medical therapy. Retrospective study of 401 consecutive patients undergoing PEA at our institution between August2005 and March2020 was performed. Primary outcome was the need for targeted PH medical therapy postoperatively. Secondary outcomes included survival and measures of hemodynamic improvement. Females (N =203, 51%) were more likely to have preoperative home oxygen therapy (29.6% vs 11.6%, p<0.01), and to present with segmental and subsegmental disease compared to males (49.2% vs 21.2%, p<0.01). Despite similar preoperative values, females had higher postoperative pulmonary vascular resistance (final total pulmonary vascular resistance after PEA, 437Dynes∙s∙cm-5 vs 324 Dynes∙s∙cm-5 in males, p<0.01). Although survival at 10 years was not significantly different between sexes (73% in females vs 84% in males, p=0.08), freedom from targeted PH medical therapy was lower in females (72.9% vs 89.9% in males at 5 years, p<0.001). Female sex remained an independent factor affecting the need for targeted PH medical therapy after PEA in multivariate analysis (HR 2.03, 95%CI 1.03-3.98, p=0.04). Although outcomes are excellent for both sexes, females had greater need for targeted PH medical therapy in the long-term. Early reassessment and long-term follow-up of these patients are important. Further investigations into possible mechanisms to explain the differences are warranted.

Predictors of procedural complications in balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension

BackgroundBalloon pulmonary angioplasty (BPA) is an effective treatment for inoperable chronic thromboembolic pulmonary hypertension, with good results reported for residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). However, BPA is associated with complications, such as pulmonary artery perforation and vascular injury, which can lead to critical pulmonary hemorrhage requiring embolization and mechanical ventilation. Furthermore, the risk factors for occurrence of complications in BPA are unclear; therefore, this study aimed to evaluate predictors of procedural complications in BPA. MethodsIn this retrospective study, we collected clinical data (patient characteristics, details of medical therapy, hemodynamic parameters, and details of the BPA procedure) from 321 consecutive sessions involving 81 patients who underwent BPA. Procedural complications were evaluated as endpoints. ResultsBPA for residual PH after PEA was performed in 141 sessions (43.9 %), which involved 37 patients. Procedural complications were observed in 79 sessions (24.6 %), including severe pulmonary hemorrhage requiring embolization in 29 sessions (9.0 % of all sessions). No patients experienced severe complications requiring intubation with mechanical ventilation or extracorporeal membrane oxygenation. Age ≥ 75 years and mean pulmonary artery pressure ≥ 30 mmHg were independent predictors of procedural complications. Residual PH after PEA was a significant predictor of severe pulmonary hemorrhage requiring embolization (adjusted odds ratio, 3.048; 95 % confidence interval, 1.042–8.914, p = 0.042). ConclusionsOlder age, high pulmonary artery pressure, and residual PH after PEA increase the risk of severe pulmonary hemorrhage requiring embolization in BPA.

Hemodynamic Effects of Ketone Bodies in Patients With Pulmonary Hypertension.

Background Pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) are debilitating diseases with a high mortality. Despite emerging treatments, pulmonary vascular resistance frequently remains elevated. However, the ketone body 3-hydroxybutyrate (3-OHB) may reduce pulmonary vascular resistance in these patients. Hence, the aim was to assess the hemodynamic effects of 3-OHB in patients with PAH or CTEPH. Methods and Results We enrolled patients with PAH (n=10) or CTEPH (n=10) and residual pulmonary hypertension. They received 3-OHB infusion and placebo (saline) for 2 hours in a randomized crossover study. Invasive hemodynamic and echocardiography measurements were performed. Furthermore, we investigated the effects of 3-OHB on the right ventricle of isolated hearts and isolated pulmonary arteries from Sprague-Dawley rats. Ketone body infusion increased circulating 3-OHB levels from 0.5±0.5 to 3.4±0.7 mmol/L (P<0.001). Cardiac output improved by 1.2±0.1 L/min (27±3%, P<0.001), and right ventricular annular systolic velocity increased by 1.4±0.4 cm/s (13±4%, P=0.002). Pulmonary vascular resistance decreased by 1.3±0.3 Wood units (18%±4%, P<0.001) with no significant difference in response between patients with PAH and CTEPH. In the rat studies, 3-OHB administration was associated with decreased pulmonary arterial tension compared with saline administration (maximal relative tension difference: 12±2%, P<0.001) and had no effect on right ventricular systolic pressures (P=0.63), whereas pressures rose at a slower pace (dP/dtmax, P=0.02). Conclusions In patients with PAH or CTEPH, ketone body infusion improves cardiac output and decreases pulmonary vascular resistance. Experimental rat studies support that ketone bodies relax pulmonary arteries. Long-term studies are warranted to assess the clinical role of hyperketonemia. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04615754.