Lung Volume Reduction Surgery Reduces Pulmonary Arterial Hypertension Associated With Severe Lung Emphysema and Hypercapnia.

Lung volume reduction surgery (LVRS) represents a standard surgical approach for patients with severe pulmonary emphysema. One of the relevant risk factors for LVRS is the presence of pulmonary arterial hypertension (PAH). The aim of this study is to assess the postoperative changes in pulmonary arterial pressure (PAP) after LVRS for patients with severe pulmonary emphysema compared with preoperative measures. N = 61 consecutive patients with severe pulmonary emphysema and preoperative evidence for PAH (pulmonary arterial systolic pressure [PASP] ≥ 35 mmHg) were prospectively included into this study. In all patients, thoracoscopic LVRS was performed. PASP was assessed by echocardiography before surgery, early postoperatively, and 3 months after surgery. Data were prospectively recorded and analyzed retrospectively. Primary end points were the postoperative changes in PASP as well as the 90 day mortality rate. Secondary endpoints included: pulmonary function test, exercise capacity, quality of life, and dyspnea symptoms (Borg scale). Early after surgery, a significant reduction in PASP was observed at the day of discharge and at 3 month follow-up. In n = 34 patients, no tricuspid valve regurgitation was detectable anymore suggesting normal PAP. In n = 3 patients, venovenous extracorporeal lung support (VV ECLS) was already implemented preoperatively. In the remaining cases, VV ECLS was applied intraoperatively and continued postoperatively. Mean duration of postoperative ECLS support was 2 days. Four patients died due to acute right heart failure, two patients from sepsis with multiorgan failure, and one patient from acute pulmonary embolism. Ninety day mortality was 11.5 %. A significant improvement was postoperatively observed regarding the performance status, dyspnea scale, as well as quality of life. This study suggests a beneficial effect of LVRS on PAP, which may ultimately help to protect and stabilize right ventricular function. Further studies, implementing pre- and postoperative right heart catheterizations including invasive PAP evaluation, are necessary to support the findings in this study in greater detail.

The Lung Allocation Score Remains Inequitable for Patients with Pulmonary Arterial Hypertension, Even after the 2015 Revision.

Rationale: The lung allocation score (LAS) was revised in 2015 to improve waiting list mortality and rate of transplant for patients with pulmonary arterial hypertension (PAH). Objectives: We sought to determine if the 2015 revision achieved its intended goals. Methods: Using the Standard Transplant Analysis and Research file, we assessed the impact of the 2015 LAS revision by comparing the pre- and postrevision eras. Registrants were divided into the LAS diagnostic categories: group A-chronic obstructive pulmonary disease; group B-pulmonary arterial hypertension; group C-cystic fibrosis; and group D-interstitial lung disease. Competing risk regressions were used to assess the two mutually exclusive competing risks of waiting list death and transplant. Cumulative incidence plots were created to visually inspect risks. Measurements and Main Results: The LAS at organ matching increased by 14.2 points for registrants with PAH after the 2015 LAS revision, the greatest increase among diagnostic categories (other LAS categories: Δ, -0.9 to +2.8 points). Before the revision, registrants with PAH had the highest risk of death and lowest likelihood of transplant. After the 2015 revision, registrants with PAH still had the highest risk of death, now similar to those with interstitial lung disease, and the lowest rate of transplant, now similar to those with chronic obstructive pulmonary disease. Conclusions: Although the 2015 LAS revision improved access to transplant and reduced the risk of waitlist death for patients with PAH, it did not go far enough. Significant differences in waitlist mortality and likelihood of transplant persist.

Early reduction of pulmonary arterial hypertension in patients using a long-term mechanical ventricular assistance device: a cross-sectional study

ABSTRACT BACKGROUND: Severe pulmonary arterial hypertension (PAH) is a contraindication for heart transplantation (HT). It has been correlated with increased early and late mortality, mainly associated with right ventricular failure. Ventricular assistance devices (VADs) can promote reduction of intracardiac pressures and consequent reduction of PAH over the medium and long terms, thus enabling future candidature for HT. The diminution of early pulmonary pressure within this scenario remains unclear. OBJECTIVE: To evaluate the reduction of PAH and correlate data from right catheterization with the earliness of this reduction. DESIGN AND SETTING: Cross-sectional study in a general hospital in São Paulo, Brazil. METHODS: This was a retrospective analysis on the medical records of patients undergoing VAD implantation in a single hospital. Patients for whom VAD had been indicated as a bridge to candidature for HT due to their condition of constant PAH were selected. RESULTS: Four patients with VADs had constantly severe PAH. Their mean pulmonary artery systolic pressure (PASP) before VAD implantation was 66 mmHg. Over the 30-day period after the procedure, all the patients evolved with a drop in PASP to below 60 mmHg. Their new average was 36 mmHg, which was a drop of close to 50% from baseline values. The one-year survival of this sample was 100%. CONCLUSION: VAD implantation can reduce PAH levels. Early reduction occurred in all patients. Thus, use of VAD is an important bridge tool for enabling candidature for HT among patients with constantly severe PAH.

Surgical management of giant pulmonary artery aneurysms in patients with severe pulmonary arterial hypertension.

BACKGROUND AND AIM: Giant aneurysm of the pulmonary artery (PAA) is an extremely rare condition that may develop in patients with pulmonary arterial hypertension (PAH) which may be complicated by rupture, dissection or intravascular thrombus formation. The aim of this study was to examine available literature with regard to surgical strategies in patients undergoing transplantation for PAH with PAA. RESULTS: These patients were traditionally considered for heart-lung transplantation but more recently, there have been reports of successful lung transplantation with reconstruction of the pulmonary artery. CONCLUSIONS: Unless there is a mandatory indication for heart-lung transplantation, patients with PAH and PAA can undergo lung transplantation and reconstruction of the pulmonary artery without compromising the outcome.

Plasma metabolomics in the perioperative period of defect repair in patients with pulmonary arterial hypertension associated with congenital heart disease.

The quality of life and survival rates of patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) have been greatly improved by defect-repair surgery and personalized treatments. However, those who survive surgery may remain at risk of persistent PAH, the prognosis may be considerably worse than those unoperated. Dynamic monitoring of clinical measures during the perioperative period of shunt correction is therefore indispensable and of great value. In this study, we explored the plasma-metabolite profiling in 13 patients with CHD-PAH during the perioperative period of defect repair. Plasma was harvested at four time points: prior to cardiopulmonary bypass (CPB) after anesthesia (Pre), immediately after CPB (T0), 24 h (T24), and 48 h (T48) after defect repair. Untargeted metabolomics strategy based on UPLC Q-TOF MS was used to detect the metabolites. A total of 193 distinguishing metabolites were determined at different time points, enriched in pathways such as oxidation of branched-chain fatty acids. We found that 17 metabolite alterations were significantly correlated with the reduction in mean pulmonary arterial pressure (MPAP) at T48 versus Pre. Gradients in diastolic pulmonary arterial pressure (DPAP), bicarbonate in radial artery (aHCO3), bicarbonate in superior vena cava (svcHCO3), and the partial pressure of dissolved CO2 gas in radial artery (aPCO2) were positively correlated with MPAP gradient. Notably, these clinical-measure gradients were correlated with alterations in shunt-correction-associated metabolites. In total, 12 out of 17 identified metabolites in response to defect repair were increased at both T24 and T48 (all P < 0.05, except propionylcarnitine with P < 0.05 at T24). In contrast, galactinol dihydrate, guanosine monophosphate, and hydroxyphenylacetylglycine tended to decline at T24 and T48 (only galactinol dihydrate with P < 0.05 at T48). In conclusion, 17 metabolites that respond to shunt correction could be used as suitable noninvasive markers, and clinical measures, including DPAP, aHCO3, svcHCO3, and aPCO2, would be of great value in disease monitoring and evaluating future therapeutic interventions.

Lung transplantation disparities based on diagnosis for patients bridging to transplant on extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly utilized as a bridge to lung transplantation, but ECMO status is not explicitly accounted for in the Lung Allocation Score (LAS). We hypothesized that among waitlist patients on ECMO, patients with pulmonary arterial hypertension (PAH) would have lower transplantation rates. METHODS: Using United Network for Organ Sharing data, we conducted a retrospective cohort study of patients who were ≥12 years old, active on the lung transplant waitlist, and required ECMO support from June 1, 2015 through June 12, 2020. Multivariable competing risk analysis was used to examine waitlist outcomes. RESULTS: 1064 waitlist subjects required ECMO support; 40 (3.8%) had obstructive lung disease (OLD), 97 (9.1%) had PAH,138 (13.0%) had cystic fibrosis (CF), and 789 (74.1%) had interstitial lung disease (ILD). Ultimately, 671 (63.1%) underwent transplant, while 334 (31.4%) died or were delisted. The transplant rate per person-years on the waitlist on ECMO was 15.41 for OLD, 6.05 for PAH, 15.66 for CF, and 15.62 for ILD. Compared to PAH patients, OLD, CF, and ILD patients were 78%, 69%, and 62% more likely to undergo transplant throughout the study period, respectively (adjusted SHRs 1.78 p = 0.007, 1.69 p = 0.002, and 1.62 p = 0.001). The median LAS at waitlist removal for transplantation, death, or delisting were 75.1 for OLD, 79.6 for PAH, 91.0 for CF, and 88.3 for ILD (p < 0.001). CONCLUSIONS: Among patients bridging to transplant on ECMO, patients with PAH had a lower transplantation rate than patients with OLD, CF, and ILD.

Predictive role of perioperative neutrophil to lymphocyte ratio in pediatric congenital heart disease associated with pulmonary arterial hypertension.

BACKGROUND: We aimed to explore the relationship between the neutrophil to lymphocyte ratio (NLR) and the early clinical outcomes in children with congenital heart disease (CHD) associated with pulmonary arterial hypertension (PAH) after cardiac surgery. METHODS: A retrospective observational study involving 190 children from January 2013 to August 2019 was conducted. Perioperative clinical and biochemical data were collected. RESULTS: We found that pre-operative NLR was significantly correlated with AST, STB, CR and UA (P < 0.05), while post-operative NLR was significantly correlated with ALT, AST, BUN (P < 0.05). Increased post-operative neutrophil count and NLR as well as decreased lymphocyte count could be observed after cardiac surgery (P < 0.05). Level of pre-operative NLR was significantly correlated with mechanical ventilation time, ICU stay time and total length of stay (P < 0.05), while level of post-operative NLR was only significantly correlated to the first two (P < 0.05). By using ROC curve analysis, relevant areas under the curve for predicting prolonged mechanical ventilation time beyond 24 h, 48 h and 72 h by NLR were statistically significant (P < 0.05). CONCLUSION: For patients with CHD-PAH, NLR was closely related to early post-operative complications and clinical outcomes, and could act as a novel marker to predict the occurrence of prolonged mechanical ventilation.

A novel unidirectional-valved shunt approach for end-stage pulmonary arterial hypertension: Early experience in adolescents and adults.

OBJECTIVES: Despite advances in treatment of idiopathic pulmonary arterial hypertension (IPAH), there remains no medical cure, and patients can experience disease progression leading to right heart failure, progressive exercise intolerance, and death. The reversed Potts shunt (left pulmonary artery to descending aorta) was reintroduced for treatment of end-stage IPAH to permit decompression of the suprasystemic right ventricle by right to left shunting, with preservation of upper body oxygenation. The shunt has the potential to delay the need for lung transplantation and offer a treatment for those who are transplant ineligible. To optimize shunt design and avoid the potential complications of bidirectional shunting, we developed a novel approach using a unidirectional-valved shunt (UVS) in patients with IPAH with suprasystemic pulmonary arterial pressure and poor right ventricular function. METHODS: A single-center retrospective review was performed of UVS cases done at Columbia University Medical Center-New York Presbyterian between November 1, 2016, and May 1, 2019. RESULTS: Five patients (4 female; ages 12-22 years) underwent UVS. All had suprasystemic pulmonary arterial pressure, poor right ventricular function, and World Health Organization functional class IV symptoms at baseline. All patients are alive and transplant-free at latest follow-up (range 3-33 months; median 6 ± 11 months). CONCLUSIONS: The UVS may offer an alternative solution to lung transplantation in adolescents and young adults with IPAH. Longer-term follow-up is needed to determine the ultimate impact of unidirectional unloading of the right ventricle in these patients and to determine whether the UVS will enable a broader approach to the treatment of patients with IPAH.

Outcome of paediatric portopulmonary hypertension in the modern management era: A case report of 6 patients.

Portopulmonary hypertension is a rare but serious complication of portal hypertension or portosystemic shunting. Portopulmonary hypertension is an indication for liver transplantation or shunt closure. However, liver transplantation is contraindicated in patients with severe pulmonary arterial hypertension. Reported mortality rates are high in children with portopulmonary hypertension and there are scarce recommendations on its management. Our aim was to report on our real-world experience of managing portopulmonary hypertension in a specialised centre. We describe a series of 6 children with portopulmonary hypertension. Their median age at diagnosis was 13 years (range 10-15). The underlying liver conditions were cirrhosis of unknown origin (1), congenital portocaval shunts (3), biliary atresia (1), and portal vein cavernoma with surgical mesenterico-caval shunt (1). Median mean pulmonary arterial pressure was 47 mmHg (range 32-70), and median pulmonary vascular resistance was 6.6 Wood units (range 4.3-15.4). All patients except one were treated with a combination of pulmonary arterial hypertension-specific therapy (phosphodiesterase type 5 inhibitors and/or endothelin receptor antagonists and/or prostacyclin analogues). Three patients then benefited from shunt closure and the others underwent liver transplantation. Five patients showed improvement or stabilisation of pulmonary arterial hypertension with no deaths after a mean follow-up of 39 months. Based on our limited experience, early and aggressive treatment with a combination of pulmonary arterial hypertension-specific therapy significantly improves patients' haemodynamic profile and enables the performance of liver transplantation and shunt closure with satisfactory outcomes.

Stem/Progenitor Cells and Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by endothelial dysfunction and vascular remodeling. Despite significant advancement in our understanding of the pathogenesis of PAH in recent years, treatment options for PAH are limited and their prognosis remains poor. PAH is now seen as a severe pulmonary arterial vasculopathy with structural changes driven by excessive vascular proliferation and inflammation. Perturbations of a number of cellular and molecular mechanisms have been described, including pathways involving growth factors, cytokines, metabolic signaling, elastases, and proteases, underscoring the complexity of the disease pathogenesis. Interestingly, emerging evidence suggests that stem/progenitor cells may have an impact on disease development and therapy. In preclinical studies, stem/progenitor cells displayed an ability to promote endothelial repair of dysfunctional arteries and induce neovascularization. The stem cell-based therapy for PAH are now under active investigation. This review article will briefly summarize the updates in the research field, with a special focus on the contribution of stem/progenitor cells to lesion formation via influencing vascular cell functions and highlight the potential clinical application of stem/progenitor cell therapy to PAH.

Aspergillus mediastinitis in a post-operative immunocompetent child.

Post-operative Aspergillus mediastinitis is regarded to be a devastating infection, usually affecting patients undergoing cardiothoracic surgery with specific predisposing factors characterised by a high mortality and chronic morbidity. Patient outcome after such a complication is extremely poor despite antifungal therapy and surgery. We describe the case of an immunocompetent 2-month-old child with obstructed supracardiac total anomalous pulmonary venous circulation (TAPVC) and severe pulmonary artery hypertension, who underwent TAPVC repair through median sternotomy and developed post-operative mediastinitis due to Aspergillus flavus.

Endothelin-1 induces lysyl oxidase expression in pulmonary artery smooth muscle cells.

The increase in thickening of the arterial wall of pulmonary arterial hypertension (PAH) includes cellular proliferation as well as matrix deposition and interrupted internal elastic lamina (IEL) consisting of a thick homogeneous sheet of elastin. Little is, although, known about the detail of IEL formation in PAH. Endothelin-1 is overexpressed in pulmonary arterioles of PAH. We aimed to examine the expression of genes contributing to IEL formation in pulmonary artery smooth muscle cells (PASMCs) especially focused on lysyl oxidase (LOx), an exreacellular matrix enzyme that catalyzes the cross-linking of collagens or elastin. We quantified mRNA expressions of genes contributing to IEL formation including LOx in PASMCs using real-time quantitative polymerase chain reaction. We stimulated human PASMCs with endothelin-1 with prostacyclin or trapidil. Endothelin-1 significantly increased LOx expression. Prostacyclin and trapidil restored endothelin-1-induced LOx expression to the basal level. Endothelin-1 increased LOx expression strongly in PASMCs from PAH patients compared to those from controls. Trapidil reduced LOx expression only in PASMCs from PAH patients. Overexpressed endothelin-1 in PAH patients can increase expression of LOx and agitate cross-linking of elastin and collagen, resulting in ectopic deposition of these in the vascular media.

Incidental diagnosis of a large aortopulmonary window with reversible pulmonary arterial hypertension in adult age and its surgical management.

Aortopulmonary window (APW) is a rare congenital cardiac condition. A large number of patients with a large APW usually die within 1 year of age. It is extremely rare to find cases of APW surviving till adult age and it is still rare to surgically treat such patients who are incidentally detected in adult age because such subsets of patients invariably have associated pulmonary vascular obstructive disease in advanced stage and thus there is therapeutic dilemma to surgically correct these patients. Although cases of uncorrected AP window presenting in adulthood have been reported but literature on surgically treated AP window in adult populations is limited. We describe case of APW in a 26-year-old male patient who was diagnosed incidentally while suspecting infective endocarditis and was subsequently surgically closed successfully with polytetrafluoroethylene patch after confirming reversibility of pulmonary arterial hypertension which is the key for successful outcome.

Improved method for the catheterization of the right ventricle in a rat model of pulmonary artery hypertension.

Ventricle catheterization in the rat is widely practiced in cardiopulmonary research. The catheters deployed are either fluid filled or solid tip pressure or pressure-volume catheters. The access to the right ventricle is through the right jugular vein, most commonly without direct visualization such as fluoroscopy. Advancement of the catheter tip is aided by visualizing the pressure signals of the monitoring/recording systems used. This approach may present challenges due to various reasons, including the stiffness of new catheters, their dimensions or anatomical changes associated with the animal disease model. In this article, we present a novel approach, which has been optimized, successfully validated surgically and adopted in current projects. It has been shown to improve both the overall quality of the signals recorded and the time to access the right ventricle, thus reducing the overall time of surgery. The method presented in this article is safe, easy to reproduce and does not require additional skills compared to a more 'standard' approach.

Use of a Three-Dimensional Model in Lung Transplantation for a Patient With Giant Pulmonary Aneurysm.

Management of a giant pulmonary trunk aneurysm in lung transplantation is a challenge. Herein, we present a patient undergoing replacement of the giant pulmonary artery aneurysm with a donor's aorta in bilateral lung transplantation for idiopathic pulmonary arterial hypertension. A plastic three-dimensional model of the pulmonary artery aneurysm created accurately based on computed tomography data allowed us to simulate the procedure on the back table. Our intraoperative findings and management are discussed in this article.

Lung transplantation for pulmonary hypertension with giant pulmonary artery aneurysm.

BACKGROUND: Aneurysm of the main pulmonary artery trunk (PAA) is a rare but severe complicating factor in patients suffering from pulmonary arterial hypertension (PAH). Many centers consider PAA an indication for a heart-lung transplantation. We aimed to summarize our institutional experience with a lung-only strategy in this complex group of patients. METHODS: We performed a retrospective single-center analysis of patients with PAH and a severe PAA who underwent lung transplantation between January 1996 and November 2018. RESULTS: A total of 127 patients with PAH underwent lung transplantation during the study period. Seven patients presented with severe PAA (mean diameter, 70.4 mm). Donor lungs were procured together with the main pulmonary artery (PA). In the recipient, cardiopulmonary bypass with bicaval cannulation was established, and bilateral pneumonectomy together with resection of the entire PA trunk was performed. The right donor lung was implanted, and the attached PA trunk was pulled through behind the superior vena cava and ascending aorta. Anastomosis was performed just above the level of the pulmonary valve. Thereafter, the left lung was implanted by reconnecting the left PA to the main PA trunk. All but 1 patient, who died from sepsis on postoperative day 13, were successfully discharged. CONCLUSIONS: To the best of our knowledge, this is the largest published experience of patients with PAH and severe PAA who underwent lung transplantation. We show that these patients are eligible for double lung transplantation and do not require heart-lung transplantation.

Surgical experience with cor triatriatum repair beyond infancy.

BACKGROUND: Cor triatriatum is an exceedingly rare congenital heart defect which can present at any age depending upon the presence of associated cardiac anomalies and the size of communication between the common chamber and the left atrium. Our aim is to present 10 years surgical outcome of cor triatriatum repair in patients who present beyond infancy. METHODS: On going through our institute's surgical database from January 2009 to June 2019 for cor triatriatum, 14 patients were found to have undergone the surgical correction. Their demographic profile and midterm outcome in terms of mortality, functional status, and cardiac function was assessed. RESULTS: There were total 14 patients with slight female predominance (57.14%) who underwent cor triatriatum surgical repair. The mean age at the time of surgery was 12.14 ± 9.97 years ranging from 1 to 29 years. Associated congenital cardiac defects were seen in 12 (85.71%) patients with atrial septal defect being the most common. Partial anomalous pulmonary venous connection was seen in 4 (28.57%) patients. Eight (57.14%) patients had severe pulmonary hypertension preoperatively. All but two patients showed marked reduction in pulmonary artery pressures postoperatively. All the patients underwent excision of the membrane and repair of associated cardiac defects simultaneously. There was no early or midterm mortality or any reintervention over a mean follow-up period of 58.06 ± 30.73 months (range 20-120 months). CONCLUSION: The early and midterm surgical outcome of cor triatriatum is excellent even in patients who present beyond infancy with reversible pulmonary artery hypertension.

Imaging and the Lung Transplant Patient.

Lung transplantation can prolong and improve quality of life for patients affected by end-stage lung disease. Potential lung transplant patients undergo a rigorous preoperative assessment that includes multiple medical imaging studies. These studies provide information that help physicians determine whether the patient is a surgical candidate, as well as the surgical technique that should be used during transplantation. Imaging studies also are used in long-term care to detect complications in patients after lung transplantation.