Pulmonary Thromboendarterectomy Surgery Research Articles

Abstract 4115531: Relationship between Ventricular Workload and Functional Response to Balloon Pulmonary Angioplasty (BPA) Therapy for Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Background: WHO functional classification (FC) is used to evaluate clinical response to BPA therapy and is associated with hemodynamic improvements in CTEPH patients. The relationships between FC and specific metrics of left and right ventricular workload during BPA remain unclear. Methods: CTEPH patients who underwent at least six BPA sessions and were included in the UCSD BPA registry were included for analysis. Left ventricular (LV) and right ventricular (RV) cardiac power output (CPO) and stroke work index (SWI) using thermodilution cardiac output were measured, along with FC, during each BPA session. BPA “responders” showed improved FC from III/IV at baseline to I/II after BPA therapy. BPA “non-responders” had unchanged FC III/IV symptoms before and after BPA therapy. ANOVA and Student T tests were used and P-value <0.05 was significant. Results: A total of 66 subjects (55.5% female, BMI 28.3±6.10kg/m 2 ,16.7% prior pulmonary thromboendarterectomy surgery) were enrolled. Greater subject functionality by FC was significantly associated with higher LVCPO (class IV to I: 0.88±0.15, 0.94±0.28, 1.08±0.31, 0.95±0.27 watt; p<0.001), higher LVSWI (29.4±6.6, 35.6±9.4, 40.8±8.8, 43.4±11.1 g*m/beat/m 2 ; p<0.001), and lower RVCPO (0.37±0.10, 0.34±0.12, 0.34±0.14, 0.24±0.09 watt; p=0.003). RVSWI was not significantly associated with FC (14.8±3.7, 15.4±5.1, 15.1±5.0, 12.5±3.3 g*m/beat/m 2 ; p=0.075). Likewise, higher mean LVCPO (1.1±0.30 vs 0.93±0.27 watt; p<0.001) and LVSWI (41.1±9.1 vs 35.2±9.4 g*m/beat/m 2 ; p<0.001), but not RVCPO or RVSWI, were observed in subjects with FC I/II versus FC III/IV symptoms. BPA responders versus non-responders had higher overall LVCPO (1.01±0.27 vs 0.89±0.27 watt; p<0.001) and LVSWI (39.0±8.9 vs 33.2±8.4 g*m/beat/m 2 ; p<0.001), but not RVCPO (0.33±0.13 vs 0.34±0.13 watt; p=0.465) or RVSWI (15.2±4.8 vs 14.9±5.1 g*m/beat/m 2 ; p=0.694). Responders also had higher baseline LVSWI (p=0.029) and post-BPA LVSWI (p=0.028) compared to non-responders. Conclusions: CTEPH patient functionality and symptoms during BPA therapy are associated with metrics of left and right ventricular workload. Patients with more severe FC III/IV symptoms produce lower LV workload. Treatment responders with improved FC after BPA therapy achieve higher overall, pre-BPA, and post-BPA LV workload. Specific metrics of ventricular workload may be helpful determinants of CTEPH patient symptoms and BPA treatment response.

Abstract 4113405: The Role of Cardiac Power Output and Stroke Work Index in Balloon Pulmonary Angioplasty Therapy for Chronic Thromboembolic Pulmonary Hypertension

Background: Right ventricular (RV) and left ventricular (LV) measures of cardiac power output (CPO) and stroke work index (SWI) are existing markers of cardiac function and clinical outcomes. These metrics have not been used to evaluate the effects of balloon pulmonary angioplasty (BPA) therapy in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: CTEPH patients who underwent at least six BPA sessions and were included in the UC San Diego BPA registry were included for analysis. Left and right ventricular CPO and SWI during each session were recorded. Cardiac output was measured using the thermodilution technique. Differences in continuous variable measurements before versus after BPA therapy were evaluated using the Student T-test. P-value <0.05 was significant. Results: A total of 66 subjects underwent six consecutive BPA sessions (55.5% female, BMI 28.3±6.10kg/m 2 ,16.7% prior pulmonary thromboendarterectomy surgery) and were included for analysis. Measurements of RV function, including RVCPO (Pre-BPA 0.38±0.14 vs Post-BPA 0.30±0.13 W, p=0.001)(Figure 1) and RVSWI (Pre-BPA 16.52±5.09 vs Post-BPA 14.14±4.00 g*m/beat/m 2 , p=0.004) significantly decreased after BPA therapy. Measurements of LV function, including LVCPO (Pre-BPA 1.00±0.32 vs Post-BPA 1.04±0.31 W, p=0.523) (Figure 2) and LVSWI (Pre-BPA 37.13±10.14 vs Post-BPA 39.73±9.37 g*m/beat/m 2 , p=0.152) did not change significantly after BPA therapy. The ratio of LVCPO/RVCPO increased in stepwise fashion from baseline to the last BPA session (2.82± 0.95 vs. 3.54±1.31 W, p<0.001)(Figure 3). Conclusions: Hemodynamic work expended by the RV decreased after BPA therapy, while work expended by the LV remained unchanged during BPA therapy. The ratio of LV-to-RV work increased in a stepwise manner during consecutive BPA sessions. These measurements may be useful parameters to monitor clinical response to BPA therapy.

Effect of Deep Hypothermia (18°C) on Dioxygen Metabolism During Pulmonary Thromboendarterectomy Surgery

Objectives: The aim of this physiological pilot study was to investigate the effect of deep hypothermia on oxygen extraction (OE) and consumption (VO2) in normothermic conditions (36-37°C) then at different stages of cooling: 30°C, 25°C and 18°C. Design: For three months, we conduct a prospective study on patients that underwent pulmonary thromboendarterectomy. Settings: This is a single center study done in a university teaching hospital. ParticipantsPatients that underwent pulmonary thromboendarterectomy during the inclusion period. InterventionsHemodynamic and biological data were recorded from arterial and venous blood gas samples withdrawn first at normothermia, then at 30°C, 25°C and 18°C.. Measurements and Main Results24 patients were included in the final analysis. Indexed VO2 decreased from 65.9 ml to 25.1 ml of O2/min/m2 between 36°C and 18°C (p<0.001). The OE decreased from 18% to 9% between 36°C and 18°C (p<0.001). At normal temperature and at 18°C, the median venoarterial difference of O2 bound to hemoglobin was 2.22 [1.68-2.58] and 0.03 [0.01-0.07] ml of O2/100 ml of blood, respectively (p<0.001). Whereas the median venoarterial difference of dissolved O2 was 0.78 [0.66-0.92] and 1.09 [1.03-1.32] ml of O2/100 ml of blood, respectively (p=0.0013). Conclusion: There is a VO2 and OE decrease of more than half of their baseline value at 18°C. Seeing that the metabolic needs are essentially supplied from dissolved O2 during cooling from 30°C to 18°C, we suggest that PaO2 should be increased during the period of cooling and/or of deep hypothermia to prevent hypoxia.

(644) - Long-Term Outcome of Patients with Chronic Thromboembolic Pulmonary Hypertension Following Pulmonary Thromboendarterectomy Surgery - Results from a Referral Centre in India

(644) - Long-Term Outcome of Patients with Chronic Thromboembolic Pulmonary Hypertension Following Pulmonary Thromboendarterectomy Surgery - Results from a Referral Centre in India

Balloon pulmonary angioplasty in the current era of CTEPH treatment: How did we get here?

Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by persistent organized thromboembolic obstruction of the pulmonary arteries from incompletely resolved pulmonary embolism. The treatment of choice is pulmonary thromboendarterectomy (PTE) surgery and all patients should be evaluated for operability candidacy. Despite advancements in PTE technique allowing more segmental-subsegmental surgeries, up to a third of patients with CTEPH may still be considered inoperable. Over the past decade, there have been increasing treatment options for these inoperable CTEPH patients. Balloon pulmonary angioplasty (BPA) is a percutaneous-based interventional treatment option for select CTEPH cases. Early BPA experiences were plagued by high complication rates, but further refinements in technique and equipment pioneered by Japan led to the worldwide spread and adoption of BPA. Multiple centers have shown that patients experience significant improvements in hemodynamics, quality of life, exercise capacity, and survival with BPA treatment. There remain many questions on best practices, but BPA has evolved into a pivotal cornerstone of CTEPH treatment.

Repeat pulmonary thromboendarterectomy outcomes: A 15-year single-center retrospective review

ObjectiveChronic thromboembolic pulmonary hypertension is potentially curable via pulmonary thromboendarterectomy. A minority of patients experience recurrence of their symptoms and are eligible for repeat pulmonary thromboendarterectomy. However, little data exist regarding risk factors and outcomes for this patient population. MethodsWe performed a retrospective review of the University of California San Diego chronic thromboembolic pulmonary hypertension quality improvement database, including all patients who underwent pulmonary thromboendarterectomy from December 2005 to December 2020. Of the 2019 cases performed during this period, 46 were repeat pulmonary thromboendarterectomy procedures. Demographics, preoperative and postoperative hemodynamics, and surgical complications were compared between the repeat pulmonary thromboendarterectomy group and 1008 first pulmonary thromboendarterectomy group. ResultsRepeat pulmonary thromboendarterectomy recipients were more likely to be younger, to have an identified hypercoagulable state, and to have higher preoperative right atrial pressure. Etiologies of recurrent disease include incomplete initial endarterectomy, discontinuation of anticoagulation (noncompliance or for medical reasons), and anticoagulation treatment failure. Patients who received repeat pulmonary thromboendarterectomy had significant hemodynamic improvement, but less pronounced compared with patients who received first pulmonary thromboendarterectomy. Repeat pulmonary thromboendarterectomy was associated with an increased risk of postoperative bleeding, reperfusion lung injury, residual pulmonary hypertension, and increased ventilator, intensive care unit, and hospital days. However, hospital mortality was similar between the groups (2.2% vs 1.9%). ConclusionsThis is the largest reported series of repeat pulmonary thromboendarterectomy surgery. Despite an increase in postoperative complications, this study demonstrates that repeat pulmonary thromboendarterectomy surgery can result in significant hemodynamic improvement with acceptable surgical mortality in an experienced center.

Single-Cell Analysis Reveals Distinct Immune and Smooth Muscle Cell Populations that Contribute to Chronic Thromboembolic Pulmonary Hypertension.

Rationale: Chronic thromboembolic pulmonary hypertension (CTEPH) is a sequela of acute pulmonary embolism (PE) in which the PE remodels into a chronic scar in the pulmonary arteries. This results in vascular obstruction, pulmonary microvasculopathy, and pulmonary hypertension. Objectives: Our current understanding of CTEPH pathobiology is primarily derived from cell-based studies limited by the use of specific cell markers or phenotypic modulation in cell culture. Therefore, our main objective was to identify the multiple cell types that constitute CTEPH thrombusy and to study their dysfunction. Methods: Here we used single-cell RNA sequencing of tissue removed at the time of pulmonary endarterectomy surgery from five patients to identify the multiple cell types. Using invitro assays, we analyzed differences in phenotype between CTEPH thrombus and healthy pulmonary vascular cells. We studied potential therapeutic targets in cells isolated from CTEPH thrombus. Measurements and Main Results: Single-cell RNA sequencing identified multiple cell types, including macrophages, T cells, and smooth muscle cells (SMCs), that constitute CTEPH thrombus. Notably, multiple macrophage subclusters were identified but broadly split into two categories, with the larger group characterized by an upregulation of inflammatory signaling predicted to promote pulmonary vascular remodeling. CD4+ and CD8+ T cells were identified and likely contribute to chronic inflammation in CTEPH. SMCs were a heterogeneous population, with a cluster of myofibroblasts that express markers of fibrosis and are predicted to arise from other SMC clusters based on pseudotime analysis. Additionally, cultured endothelial, smooth muscle, and myofibroblast cells isolated from CTEPH fibrothrombotic material have distinct phenotypes from control cells with regard to angiogenic potential and rates of proliferation and apoptosis. Last, our analysis identified PAR1 (protease-activated receptor 1) as a potential therapeutic target that links thrombosis to chronic PE in CTEPH, with PAR1 inhibition decreasing SMC and myofibroblast proliferation and migration. Conclusions: These findings suggest a model for CTEPH similar to atherosclerosis, with chronic inflammation promoted by macrophages and T cells driving vascular remodeling through SMC modulation, and suggest new approaches for pharmacologically targeting this disease.

Actigraphy-based sleep and activity measurements in intensive care unit patients randomized to ramelteon or placebo for delirium prevention

Patients in the ICU often sleep poorly for various reasons, which may predispose to delirium. We previously conducted a clinical trial in which we tested the efficacy of ramelteon, a melatonin-receptor agonist used to treat insomnia, versus placebo, in preventing ICU delirium in patients who underwent elective pulmonary thromboendarterectomy (PTE) surgery. Here we examine sleep, activity, and circadian patterns, measured with actigraphy, to understand changes in these metrics with our intervention and in those with and without delirium. Participants wore wrist actigraphy devices while recovering post-operatively in the ICU. For sleep analysis, we extracted total sleep time and sleep fragmentation metrics over the 22:00 to 06:00 period nightly, and daytime nap duration from the daytime period (0:600 to 22:00) for each participant. For activity analyses, we extracted the following metrics: total daytime activity count (AC), maximum daytime AC, total nighttime AC, and maximum nighttime AC. Next, we performed a nonparametric circadian analysis on ACs over each 24-h day and extracted the following: interdaily stability (IS), intra-daily variability (IV), relative amplitude (RA), and low and high periods of activity (L5 and M10) as well as their start times. These metrics were compared between patients who received ramelteon versus placebo, and between patients who became delirious versus those who did not develop delirium. We additionally made comparisons between groups for daytime and nighttime light levels. No differences in sleep, activity, circadian metrics or light levels were found between drug groups. Delirious patients, when compared to those who were never delirious, had a lower IS (0.35 ± 0.16 vs. 0.47 ± 0.23; P = 0.006). Otherewise, no differences in IV, L5, M10, or RA were found between groups. L5 and M10 activity values increased significantly over the post-extubation for the whole cohort. No differences were found for daytime or nighttime light levels between groups. Overall, ramelteon did not impact sleep or circadian metrics in this cohort. Consistent with clinical experience, delirious patients had less inter-daily stability in their rest-activity rhythms. These data suggest that actigraphy might have value for individual assessment of sleep in the ICU, and for determining and detecting the impact of interventions directed at improving sleep and circadian activity rhythms in the ICU.Trial registration: REGISTERED at CLINICALTRIALS.GOV: NCT02691013. Registered on February 24, 2016 by principal investigator, Dr. Robert L. Owens.

The use of ketamine as an induction agent for anesthesia in pulmonary thromboendarterectomy surgery: A case series.

Pulmonary thromboendarterectomy (PTE) surgery is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension (CTEPH). The induction of anesthesia in patients with severe pulmonary hypertension (PHT) can be challenging, with a risk of cardiovascular collapse. The administration of ketamine in patients with PHT is controversial, with some recommendations contraindicating its use. However, ketamine has been used safely in children with severe PHT. We present a retrospective case series of adult patients with severe PHT presenting for PTE surgery, using intravenous ketamine as a co-induction anesthetic agent.

Patient selection for balloon pulmonary angioplasty: Six-year results from a high volume PTE surgical center.

Chronic thromboembolic pulmonary hypertension (CTEPH) is the result of incompletely resolved pulmonary emboli (PE) that lead to chronic right heart failure. The two mechanical treatment options are pulmonary thromboendarterectomy (PTE) and balloon pulmonary angioplasty (BPA). There are no formal criteria for BPA patient selection and treatment decisions vary according to a center's experience with BPA and PTE. We performed a retrospective review of consecutive patients treated with PTE and BPA at UCSD from March 2015 to 2021. Clinical and hemodynamic data were collected. Patients were categorized according to the rationale for BPA. One hundred fifty three patients underwent 643 BPA sessions, and 1104 patients underwent PTE. Patients selected for PTE had worse baseline hemodynamics with mean pulmonary artery pressure 41.1 ± 11.7 versus 34.6 ± 11.2 mmHg, p < 0.001. 59% of patients selected for BPA had surgically inaccessible disease, 21% had residual CTEPH after PTE, 10% had a discordance between disease burden and symptoms/hemodynamics, 7% had comorbidities that prevented PTE and 3% refused PTE surgery. 28% of patients who underwent PTE had exclusively level III or IV disease based on surgical specimen. There were no BPA procedure-related mortalities and minor pulmonary vascular complication rates during BPA were 9.2%. The most common reason for BPA selection was surgically inaccessible disease followed by residual CTEPH after PTE. Almost one third of patients who underwent PTE had exclusively distal disease by surgical criteria and might have been directed to BPA at a less experienced surgical center.

Guest Editors’ Memo

Chronic thromboembolic pulmonary hypertension (CTEPH) is unique among the many etiologies of pulmonary hypertension (PH), in that it can be treated very effectively, even cured, with the surgical extraction of occlusive thrombo-fibrotic lesions via pulmonary thromboendarterectomy (PTE) surgery. More recently, balloon pulmonary angioplasty (BPA) has emerged as a viable option for patients who cannot or should not be operated upon, and for those with residual disease after PTE. Arguably, BPA is one of the major advancements in pulmonary vascular disease over the past 2 decades, although surgical therapy with PTE remains the treatment of choice whenever feasible. Effective PH-targeted medical therapy is also available, and increasingly multimodality approaches including a combination of these treatment options are being utilized in expert centers to achieve the best outcomes. And yet, CTEPH remains a vastly under-recognized disease, with considerable delays and confusion in its diagnosis. As a result, many patients are still not being effectively treated. This issue of Advances in Pulmonary Hypertension represents an effort to update our readers on the key current diagnostic and therapeutic approaches for CTEPH.In “Post-Pulmonary Embolism Follow-Up and Epidemiology of Chronic Thromboembolic Pulmonary Hypertension”, Jasuja and colleagues provide a comprehensive framework of the many issues that need to be addressed in follow-up after an acute pulmonary embolism (PE). In addition, the authors review the available evidence and challenges on the epidemiology and risk factors for CTEPH, as well as the evolving understanding of the post-PE syndrome.In the article “Diagnostic Evaluation of CTEPH”, Vaidya and Forfia describe the multiple steps and testing needed to arrive at the correct diagnosis of CTEPH, including several chest imaging studies that can accurately identify and quantify chronic thrombo-fibrotic occlusive disease of pulmonary arteries, as well as detailed imaging and hemodynamic studies that measure the impact of occlusive disease on right ventricular afterload.The article “Pulmonary Thromboendarterectomy: Patient Selection, Techniques, Outcomes, and Recent Advances” by Madani and Higgins provides a discussion on the current role of surgical therapy for CTEPH, which remains the treatment of choice for a majority of patients.In “Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension” Serfas and Krasuski share an expert insight into patient selection, procedural technique and complications of this relatively novel interventional treatment modality for CTEPH, which is gaining an increasingly important role in management of CTEPH in expert centers.In “Medical Management of Chronic Thromboembolic Pulmonary Hypertension” Goyanes and Heresi review the medical management of CTEPH, including lifelong anticoagulation to prevent recurrent PE and PH-targeted therapy (pulmonary vasodilators) directed at the concomitant microscopic vasculopathy. The authors detail the available literature and current knowledge gaps regarding choice of anticoagulant, patient selection for pulmonary vasodilator therapy, and the place of PH therapy in the context of PTE and BPA.Finally, in the round table discussion, Co-editors Drs. Heresi and Krasuski gather Drs. Auger, Tapson and Lang for a lively conversation on the practical aspects and current challenges in the diagnosis of CTEPH, including recognition of CTEPH after acute PE, and the use of detailed and precise imaging and hemodynamic techniques to phenotype CTEPH.We are confident our readers will find this issue informative and we sincerely thank all the contributors for their efforts and time devoted to this issue.

PH Roundtable: Tailoring CTEPH Imaging for Evaluation and Postintervention Assessment—What Works and What’s New?

PH Roundtable: Tailoring CTEPH Imaging for Evaluation and Postintervention Assessment—What Works and What’s New?

Pulmonary thromboendarterectomy and pulmonary haemorrhage.

Pulmonary thromboendarterectomy surgery is the recommended treatment for patients with chronic thromboembolic pulmonary hypertension. Massive intraoperative pulmonary haemorrhage with bleeding into the airway is a rare complication, and it typically presents as cardiopulmonary bypass flow is reduced and blood begins to flow through the pulmonary circulation. Immediate management includes maintaining extracorporeal circulation to reduce blood flow through the pulmonary circulation, isolation of the affected lung, while the surgeon identifies and repairs the site of haemorrhage.

Resting heart rate as a preoperative predictor of postoperative atrial fibrillation after pulmonary thromboendarterectomy.

As a marker of the autonomic nervous system, resting heart rate is a predictor of postoperative atrial fibrillation (POAF). However, its predictive value for POAF after pulmonary thromboendarterectomy (PTE) has not been adequately studied. We enrolled 97 patients who underwent PTE in our hospital from December 2016 to November 2021 in this retrospective study. Almost all preoperative characteristics, including electrocardiogram, demographics, hematologic and biochemical indices, echocardiography, and pulmonary hemodynamics, were compared between patients with and without POAF. Multivariate logistic regression analysis was used to identify the independent risk factors for POAF after PTE. Overall, 21 patients (21.6%) suffered from POAF after PTE. Compared with patients without POAF, those with POAF were older (p = .049), with a higher resting heart rate (p = .012), and higher platelet count (p = .040). In the binary logistic regression analysis, the resting heart rate (odds ratio [OR] = 1.043, 95% confidence interval [CI] = 1.009-1.078, p = .012) and age (OR = 1.051, 95% CI = 1.003-1.102, p = .037) were independent risk factors for POAF after PTE. The optimal cutoff point of resting heart rate was 89.5 with sensitivity and specificity of 47.6% and 77.6%. When the cutoff value of the age was 54.5, its sensitivity for predicting POAF was 71.4%, with a specificity of 59.2%. POAF is common after PTE surgery, and the incidence may be underestimated. The resting heart rate and age are independent preoperative risk factors for POAF after PTE. Considering the lower predictive power of the resting heart and age, further large-scale studies are needed.

Abstract 9968: Classification and Treatment of Post-Operative Atrial Arrhythmias in Pulmonary Thromboendarterectomy Surgery

Background: Atrial arrhythmias (AA) are common after cardiac surgeries including pulmonary thromboendarterectomy (PTE) surgery. However, the arrhythmia classification, treatment and impact of these AA after PTE surgery is unclear. Hypothesis: We hypothesized that most AA after PTE are paroxysmal and have a significant impact on post-operative outcomes. Methods: We reviewed the charts of 883 consecutive patients who were referred to University of California San Diego for PTE. Demographics, lab results and imaging were extracted from chart review. Predictors and outcomes were analyzed using a multivariate backward logistic regression model or independent samples t test respectively. Results: A total of 158 patients (18%) of patients developed an atrial arrhythmia. Paroxysmal atrial fibrillation (AF) was most common (72%, n=113). Persistent AF occurred in 8% of patients (n=12) and atrial flutter occurred in 21% (n=33) after PTE. The average days to onset of AA was 5.6 +/-4.4 days. Strongest predictors of AA (shown in attached figure) were chronic obstructive pulmonary disease (OR 2.8, p=&lt;0.01) and epicardial pacing requirement (OR 4.6, p=&lt;0.01). Patients who developed an AA had significantly prolonged post-operative length of stays (LOS) (14.7 days vs 11.9 days, p=&lt;0.01) compared to those who did not. Amiodarone was given in 73% (n=115) of patients and cardioversion was performed in 15% (n=23) of AA patients. Conclusions: AA are common after PTE surgery. Paroxysmal atrial fibrillation was seen most commonly. Patients who had COPD or required epicardial pacing were at highest risk of developing an AA. AA have a significantly prolonged post-operative LOS. The majority of patients received antiarrhythmic therapy with amiodarone (73%) and a minority underwent cardioversion (15%)

Abstract 10221: Premature Ventricular Contractions in Chronic Thromboembolic Pulmonary Hypertension Undergoing Pulmonary Thromboendarterectomy Surgery

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and progressive subtype of severe pulmonary hypertension. Premature ventricular contractions (PVC) are common and can be a marker of cardiomyopathy. We aimed to describe the incidence, location and predictors of PVCs in CTEPH patients undergoing Pulmonary Thromboendarterectomy surgery (PTE). Hypothesis: PVCs are common in CTEPH patients and the right ventricle would be the most common location of PVCs. Methods: We reviewed the charts of 883 consecutive patients who were referred for PTE. 12-lead ECGs were reviewed for presence of PVC. Demographics, baseline lab and imaging were extracted from chart review. Predictors of PVCs were analyzed using multivariate backward logistic regression. PVC location was identified using standard location algorithms based on the 12-lead ECG. Results: Overall, 6.5% (n=57) of patients had PVCs. Surprisingly, the majority of PVCs originated from the left ventricle (75.4%, N=43). The most common location was non-outflow tracts with LV non-outflow tract (59.3%, N=34), followed by RV non-out tract (19.3%, N=11). Within the non-outflow tract region, the majority of the PVC location appeared to be septal related (moderator band, posterior fascicle or posterior medial papillary muscle). The mitral annulus was also a common location (15.8%, N=9). In a multivariate model, heart failure (OR 2.8, p=&lt;0.01), coronary artery disease (CAD) (OR 2.8, p=&lt;0.01), sleep apnea (OR 2.2, p=0.02) and obesity (OR 1.6, p=&lt;0.01) increased the odds of having PVCs. Conclusions: PVCs are not uncommon in CTEPH patients undergoing PTE surgery. Overall, 6.5% of patients had PVCs with the majority originating in the left ventricle (75.4%). Using standard ECG criteria, the most common location was the LV non-outflow tract. Heart failure, CAD, sleep apnea and obesity increased the odds of having a PVC.

Abstract 10216: Sinus Node Dysfunction After Pulmonary Thromboendarterectomy Surgery

Background: Pulmonary Thromboendarterectomy (PTE) is a specialized cardiac surgery for treating chronic thromboembolic pulmonary hypertension (CTEPH). Sinus node dysfunction is seen in this population as patients often require epicardial pacing after cardiac surgeries. We aimed to define the incidence, predictors, and outcomes of sinus node dysfunction after PTE surgery. Hypothesis: We hypothesized that sinus node dysfunction requiring epicardial pacing is common after PTE surgery. Methods: We reviewed the charts of 883 consecutive patients who were referred to University of California San Diego for PTE. Demographics, lab results and imaging were extracted from chart review. Predictors and outcomes were analyzed using multivariate backward logistic regression model or independent samples T test respectively. Results: Overall, 60% (n=533) of patients required epicardial pacing for an average of 3.9 +/- 2.2 days. Strongest predictors of epicardial pacing were coronary artery disease (OR 2.6, p=&lt;0.01) and tobacco abuse (OR 2.1, p=0.01). Of the patients who required epicardial pacing, only 1% (n=4) required permanent pacemaker placement. Patients who required epicardial pacing had significantly longer post-operative length of stays (12.9 days vs 11.3 days, p=&lt;0.01) and ventilator days (2.3 days vs 1.8 days, p=0.02). Conclusions: The majority of patients undergoing PTE for chronic thromboembolic pulmonary hypertension develop sinus node dysfunction requiring temporary epicardial pacing. The mechanism of sinus node dysfunction appears transient as the average pacing requirement is 3.9 +/- 2.2 days, and ultimately only 1% (n=4) require permanent pacemaker placement. Patients who required epicardial pacing had significantly longer post-operative length of stay and ventilator days.

Abstract 12433: Distinct Immune and Mesenchymal Populations Identified by Single Cell RNA Sequencing Contribute to Chronic Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a sequelae of acute pulmonary embolism (PE) in which the PE remodels into a chronic scar in the pulmonary arterial system. This results in vascular obstruction, small vessel arteriopathy and pulmonary hypertension. Previous studies have attempted to identify cells that contribute to CTEPH thrombus but have been limited by the use of specific cell markers or phenotypic modulation after cell growth in culture. Here we have used single cell RNA sequencing (scRNAseq) of samples of CTEPH thrombus removed at the time of pulmonary thromboendarterectomy (PTE) surgery to identify clusters of macrophages, T cells, smooth muscle cells and endothelial cells in CTEPH thrombus. We identified that multiple macrophage subclusters, many of which have an inflammatory phenotype. T cells were a heterogeneous population consisting of CD4+ and CD8+ T cells that are predicted to be inflammatory and also promote vascular remodeling. In the smooth muscle cell cluster, a subcluster of myofibroblasts are predicted to arise from smooth muscle cells based on pseudotime analysis. Notably, cultured endothelial, smooth muscle and myofibroblast cells isolated from CTEPH thrombus have distinct phenotypes from control cells. For example, endothelial cells had reduced angiogenic potential, were proliferative and anti-apoptotic. Lastly, gene expression data identified protease-activated receptor 1 (PAR1) as a potential therapeutic target that links thrombosis to chronic PE in CTEPH. Together, these studies suggest a model in which chronic inflammation drives vascular remodeling and mesenchymal senescence in CTEPH pathogenesis and suggest new approaches for targeting this disease.

Results From the United States Chronic Thromboembolic Pulmonary Hypertension Registry: Enrollment Characteristics and 1-Year Follow-up

BackgroundThe United States Chronic Thromboembolic Pulmonary Hypertension Registry (US-CTEPH-R) was designed to characterize the demographic characteristics, evaluation, clinical course, and outcomes of surgical and nonsurgical therapies for patients with chronic thromboembolic pulmonary hypertension.Research QuestionWhat are the differences in baseline characteristics and 1-year outcomes between operated and nonoperated subjects?Study Design and MethodsThis study describes a multicenter, prospective, longitudinal, observational registry of patients newly diagnosed (< 6 months) with CTEPH. Inclusion criteria required a mean pulmonary artery pressure ≥ 25 mm Hg documented by right heart catheterization and radiologic confirmation of CTEPH. Between 2015 and 2018, a total of 750 patients were enrolled and followed up biannually until 2019.ResultsMost patients with CTEPH (87.9%) reported a history of acute pulmonary embolism. CTEPH diagnosis delays were frequent (median, 10 months), and most patients reported World Health Organization functional class 3 status at enrollment with a median mean pulmonary artery pressure of 44 mm Hg. The registry cohort was subdivided into Operable patients undergoing pulmonary thromboendarterectomy (PTE) surgery (n = 566), Operable patients who did not undergo surgery (n = 88), and those who were Inoperable (n = 96). Inoperable patients were older than Operated patients; less likely to be obese; have a DVT history, non-type O blood group, or thrombophilia; and more likely to have COPD or a history of cancer. PTE resulted in a median pulmonary vascular resistance decline from 6.9 to 2.6 Wood units (P < .001) with a 3.9% in-hospital mortality. At 1-year follow-up, Operated patients were less likely treated with oxygen, diuretics, or pulmonary hypertension-targeted therapy compared with Inoperable patients. A larger percentage of Operated patients were World Health Organization functional class 1 or 2 at 1 year (82.9%) compared with the Inoperable (48.2%) and Operable/No Surgery (56%) groups (P < .001).InterpretationDifferences exist in the clinical characteristics between patients who exhibited operable CTEPH and those who were inoperable, with the most favorable 1-year outcomes in those who underwent PTE surgery.Clinical Trial RegistrationClinicalTrials.gov; No.: NCT02429284; URL: www.clinicaltrials.gov.

PULMONARY THROMBOENDARTERECTOMY OUTCOMES IN PATIENTS WITH PRIOR STERNOTOMY

SESSION TITLE: Pulmonary Vascular Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Pulmonary thromboendarterectomy (PTE) remains the procedure of choice for the treatment of CTEPH. However, registry data suggest more than 1/3 of CTEPH patients are deemed inoperable due distal location of disease and/or comorbidities. There have been no publications of risks and outcomes in PTE patients with prior sternotomy. METHODS: We performed a retrospective review of the UCSD CTEPH quality improvement database, including all patients who underwent PTE at our institution from December 2005 to June 2019. Complete pre-and post-op data was available on 1744 PTE patients of which 105 patients were identified as having a previous sternotomy. Of those 105 patients with prior sternotomy, 42 had previous PTE and 63 had undergone other cardiac procedures. We compared these 63 patients undergoing re-entry sternotomy (Re-entry) to 1639 PTE patients without a history of prior sternotomy (controls). RESULTS: The most common cause for initial sternotomy in Re-entry patients was RA/RV clot (n=25) followed by previous CABG (n=16) and valve replacements including mitral (n = 4) and tricuspid valve (n=2). Age and preoperative mPA (39.5 vs 42.4 mmHg, p = 0.7) and PVR (514 vs 634 dynes.sec.cm-5, p= 0.27) were similar between Re-entry and controls. UCSD Level of disease, CPBP times, and number of additional procedures at the time of PTE were similar between Re-entry and controls. Re-entry sternotomy subjects had prolonged circulatory arrest times (46 ± 18 vs 36 ± 14 minutes, p=0.0007) compared to controls. Postoperative hemodynamics were comparable between Re-entry and control groups: mPA (23.8 vs 24.1 mmHg, p = 0.999) and PVR (223 vs 238 dynes.sec.cm-5, p = 0.997). Postoperatively, Re-entry subjects were more likely to require re-intubation (3.3% vs 9.5%, p=0.009), have post-op bleeding complications (11.8% vs 20.6%, p=0.045) with a trend towards increased need to return to OR (4.6% vs 9.5%, p = 0.076). Mortality was higher in the Re-entry group, but not statistically different from controls (4.8% vs 2.1%, p = 0.15). Causes of the 3 deaths for the Re-entry group included recurrent pulmonary and systemic artery thromboses (1), cardiogenic shock from acute occlusion of a pre-existing LIMA-LAD graft (1), and mediastinal hemorrhage (1). The ventilator days, ICU stay, and total hospital length of stay did not differ significantly between the two groups. CONCLUSIONS: Patients who have undergone previous sternotomy prior to PTE experience significant hemodynamic improvement with similar ventilator, ICU, and total post-operative hospital days compared to patients without prior sternotomy. However, re-entry sternotomy was associated with a higher risk of bleeding and re-intubation. CLINICAL IMPLICATIONS: Despite the increased risk, selected patients with a history of prior sternotomy have excellent outcomes and should still be considered for PTE surgery. DISCLOSURES: No relevant relationships by Anna Astashchanka, source=Web Response No relevant relationships by Timothy Fernandes, source=Web Response research support relationship with Bayer HealthCare Please note: >$100000 Added 05/21/2020 by Kim Kerr, source=Web Response, value=Grant/Research Support Consultant relationship with Actelion Please note: $1001 - $5000 Added 05/21/2020 by Kim Kerr, source=Web Response, value=Consulting fee Consultant relationship with Actelion Please note: $5001 - $20000 Added 05/20/2020 by Nick Kim, source=Web Response, value=Consulting fee Consultant relationship with Bayer Please note: $5001 - $20000 Added 05/20/2020 by Nick Kim, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Actelion Please note: $1001 - $5000 Added 05/20/2020 by Nick Kim, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Bayer Please note: $1001 - $5000 Added 05/20/2020 by Nick Kim, source=Web Response, value=Honoraria Scientific Medical Advisor relationship with Gossamer Bio Please note: $5001 - $20000 Added 05/20/2020 by Nick Kim, source=Web Response, value=Grant/Research Support Scientific Medical Advisor relationship with Sonivie Please note: $5001 - $20000 Added 05/20/2020 by Nick Kim, source=Web Response, value=Grant/Research Support Scientific Medical Advisor relationship with United Therapeutics Please note: $1001 - $5000 Added 05/20/2020 by Nick Kim, source=Web Response, value=Consulting fee Scientific Medical Advisor relationship with United Therapeutics Please note: $1001 - $5000 Added 05/20/2020 by Nick Kim, source=Web Response, value=Consulting fee Removed 05/20/2020 by Nick Kim, source=Web Response No relevant relationships by Michael Madani, source=Web Response Consultant relationship with Actelion LLC Please note: $20001 - $100000 Added 05/29/2020 by Demosthenes Papamatheakis, source=Web Response, value=Honoraria Principal Investigator relationship with Actelion Please note: $1-$1000 Added 05/30/2020 by David Poch, source=Web Response, value=No compensation Principal Investigator relationship with United Therapeutics Please note: $1-$1000 Added 05/30/2020 by David Poch, source=Web Response, value=No compensation Principal Investigator relationship with Reatta Please note: $1-$1000 Added 05/30/2020 by David Poch, source=Web Response, value=No compensation Principal Investigator relationship with Phasebio Please note: $1-$1000 Added 05/30/2020 by David Poch, source=Web Response, value=No compensation Principal Investigator relationship with Acceleron Please note: $1-$1000 Added 05/30/2020 by David Poch, source=Web Response, value=No compensation No relevant relationships by Victor Pretorius, source=Web Response