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Introduction Inhaled nitric oxide (INO) is a selective pulmonary vasodilator delivered from compressed gas cylinders filled to 2,200 psig (137.8 bar) with 800 ppm of NO in a balance of nitrogen. NO is currently FDA-approved for use in term or near-term infants with hypoxemia and signs of pulmonary hypertension in the absence of cardiac disease. INO has also been shown to improve oxygenation in adults with refractory hypoxemia. Current doctrine precludes the use of NO during military aeromedical transport owing to the requirement for large compressed gas cylinders. We performed a bench evaluation of 2 delivery systems that create NO from room air without the need for pressurized cylinders, Materials and Methods We evaluated 2 portable nitric oxide INO generation systems (LungFit PH, Beyond Air Inc, Garden City, NJ and a prototype NO generator, Odic Inc, Littleton, MA) at ground level, 8,000, and 14,000 feet (2,437 and 4,267 meter) simulated altitude in an altitude chamber. The output from each device was injected into the inspiratory limb of the ventilator circuit that was attached to a test lung. A 731 ventilator (Zoll Medical, Chelmsford, MA) and T1 (Hamilton Medical, Reno, NV) were used employing 24 combinations of ventilator settings each repeated in duplicate. An INOmax DS IR was used to measure delivered INO and NO2 via a sampling line attached in the ventilator circuit inspiratory limb. A fast response oxygen analyzer (O2CAP, Oxigraf Inc, Sunnyvale, CA) was used to measure inspired FiO2. Target INO concentration was 20 ppm. Results Across all ventilator settings, the LungFit device delivered INO was 19.8 ± 1.6 ppm, 16.1 ± 1.9 ppm, and 11.6 ± 1.7 ppm at ground level, 8,000 ft (2,437 meter), and 14,000 ft (4,267 meter), respectively. The Odic device delivered INO dose was 20.6 ± 1.4 ppm, 21.3 ± 5.5 ppm, and 20.4 ± 9.1 ppm at ground level, 8,000 ft (2,437 meter), and 14,000 ft (4,267 meter), respectively. Conclusions Both devices delivered a reliable INO dose at ground level. Altitude significantly affected INO delivery accuracy at 14,000 ft (4,267 meter) (P  < 0.01) with both devices and at 8,000 ft (2,437 meter) (P  < 0.01) with LungFit. Differences in INO dosage were not statistically significant with the Odic device at 8,000 ft (2,437 meter)(P  > 0.05) although there were large variations with selected ventilator settings. With careful monitoring, devices creating INO from room air without cylinders could be used during aeromedical transport without the need for pressurized cylinders. [ABSTRACT FROM AUTHOR]

Purpose: Although classified as group 1 pulmonary arterial hypertension (PAH), patients with systemic sclerosis-related pulmonary hypertension (SSc-PH) experience poorer clinical response to PAH therapy and increased mortality compared to those with idiopathic PAH. Due to heterogeneity in phenotypes, identifying patients likely to respond to therapy is challenging. The goal of this study was to determine clinical factors associated with hemodynamic response, defined by a > 20% reduction in pulmonary vascular resistance on repeat right heart catheterization. Methods: We applied a time-to-event model using a retrospective cohort of 39 patients with precapillary SSc-PH, defined by a mean pulmonary artery pressure of ≥ 25 mmHg and pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg on right heart catheterization. Results: Patients with PAWP ≤ 8 mmHg were nearly fourfold more likely to achieve a hemodynamic response compared to those with PAWP > 8 mmHg (HR 3.88; 95% CI: 1.20, 12.57); each 1 mmHg increase in PAWP was associated with a decreased hazard for hemodynamic response (HR 0.84; 95% CI: 0.70, 1.00). Conclusion: In patients with precapillary SSc-PH, PAWP was associated with time to hemodynamic response, suggesting the importance of subclinical cardiac disease in determining hemodynamic response to oral vasodilator therapy. [ABSTRACT FROM AUTHOR]

Prompt termination of pregnancy in patients with decompensated pulmonary arterial hypertension (PAH) is imperative for improvement of maternal hemodynamics, but such termination may also result in maternal death due to further deterioration of PAH immediately after delivery. However, there have been limited reports on whether implementation of PAH therapy with continuation of pregnancy improves the maternal outcome, especially in treatment-naïve patients with PAH. A 24-year-old woman was admitted to our hospital with a chief complaint of dyspnea (WHO functional class IV) at 22 weeks and 3 days of gestation. She was diagnosed with PAH accompanied by right heart failure and low cardiac output. Intensive treatment was initiated with inotropic agents, oxygen therapy, and PAH therapy, resulting in improvement of her hemodynamics. A caesarean section was performed at 23 weeks and 3 days. Although her pulmonary arterial pressure transiently increased with oxygenation deteriorating immediately after delivery, worsening PAH improved without mechanical circulatory support. She continued receiving pulmonary vasodilators without relapse of pulmonary hypertension for three years. The improvement of pulmonary hemodynamics prior to delivery with PAH therapy led to a favorable outcome after delivery. Pulmonary hemodynamics in pregnant patients with pulmonary arterial hypertension (PAH) can deteriorate with the continuation of pregnancy, while termination can also cause PAH surge immediately after delivery. In treatment-naïve patients with PAH, who are most likely to benefit from PAH therapy, implementation of PAH therapy with continuation, even with a decompensated status, may improve the hemodynamics prior to delivery, resulting in a favorable outcome after delivery. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a common disease affecting up to 1% of the population and at least 50% of patients diagnosed with heart failure (HF) (Hoeper et al. in Lancet Respir Med 4(4):306–322, 2016). It is estimated that PH is present in 15% to 60% of patients with valvular heart disease (VHD) which can result from an increase in pulmonary blood flow and subsequently in pulmonary venous congestion and pulmonary vascular resistance (PVR). It is important to identify the severity of PH in patients with VHD to appropriately risk stratify and manage these patients (Magne et al. in JACC Cardiovasc Imaging 8(1):83–99, 2015). In this review, we examine the diagnostic criteria for PH and its pathophysiology. We also focus on the growing evidence supporting the presence of PH secondary to VHD and describe the contemporary surgical and medical therapeutic interventions in this patient population (Fig. 1). [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a rare heterogeneous disorder in the paediatric population which is mostly associated with congenital heart disease. The management of paediatric idiopathic PAH (IPAH) is difficult due to insufficient comparative data and depends on the results of evidence-based adult studies with several pulmonary vasodilators, as well as the clinical experiences of paediatric experts. Our aim was to present the case of a 9-year-old girl who underwent several methods of treatment, including pharmacotherapy with a significant reaction to treprostinil, as well as bilateral lung transplantation. The patient's treatment was distinguished by the fact that the dose escalation was as rapid as that observed in the adult population. Due to the limited current evidence and knowledge, the initiation of treatment for these patients remains an individual choice. On the grounds of the number of non-specific symptoms, the diagnosis of this patient was a long process and based mainly on the differential diagnosis. The purpose of this paper is to study this example in order to highlight the importance of early symptoms and the quick implementation of intensive treatment. The applied methods may be useful in doubtful diagnosis processes and treatment procedures in the paediatric population. [ABSTRACT FROM AUTHOR]

Persistent pulmonary hypertension of the newborn, or PPHN, represents a challenging condition associated with high morbidity and mortality. Management is complicated by complex pathophysiology and limited neonatal specific evidence-based literature, leading to a lack of universal contemporary clinical guidelines for the care of these patients. To address this need and to provide consistent high-quality clinical care for this challenging population in our neonatal intensive care unit, we sought to develop a comprehensive clinical guideline for the acute stabilization and management of neonates with PPHN. Utilizing cross-disciplinary expertise and incorporating an extensive literature search to guide best practice, we present an approachable, pragmatic, and clinically relevant guide for the bedside management of acute PPHN. Key Points PPHN is associated with several unique diagnoses; the associated pathophysiology is different for each unique diagnosis. PPHN is a challenging, dynamic, and labile process for which optimal care requires frequent reassessment. Key management goals are adequate tissue oxygen delivery, avoiding harm. [ABSTRACT FROM AUTHOR]

Fibrosing mediastinitis (FM) is a heterogeneous disease characterized by sclerosing fibrosis of mediastinal structures. Pulmonary hypertension (PH) may complicate the course of the disease and can contribute significantly to the morbidity of FM. Due to the rarity and complexity of the disease, evidence-based guidelines are not currently available, and the optimal treatment approach is unknown. Management approaches should be individualized, and current techniques are often unsatisfactory. Here, we present two cases of PH complicating FM that were managed using pulmonary artery vasodilator therapy with excellent hemodynamic response.

Acute respiratory distress syndrome is a heterogenous syndrome with many etiologies for which there are no definitive pharmacologic treatments, despite decades of research. We explore some adjunctive pharmacologic therapies, including neuromuscular blockade, corticosteroids, and inhaled pulmonary vasodilators. Additionally, we explore some investigative therapies, including Vitamin C, beta-agonists, statins, mesenchymal stromal cells, and granulocyte-macrophage colony stimulating factor. We do discuss the potential role of steroids in acute respiratory distress syndrome with severe acute respiratory syndrome coronavirus 2 as a trigger. The standard of care, however, remains supportive care.

Abstract Background Persistent pulmonary hypertension of the newborn (PPHN) is a common neonatal condition associated with significant morbidity and mortality. First-line diagnostic and treatment options such as echocardiography and inhaled nitric oxide (iNO) are not routinely available in resource limited settings and alternative treatment modalities need to be utilized. This study was conducted to assess current diagnostic and management strategies used for PPHN in Indian neonatal intensive care units (NICUs). Methods A questionnaire in multiple choice question format was sent to practising neonatologists in India via an online survey tool between July to August 2021. Information pertaining to demographic data, diagnostic criteria and management strategies of PPHN was requested. The responses were collated and information processed. Results There were 118 respondent NICUs (response rate 74%). The majority of neonatal units (65%) admitted an average of 1–3 patients of PPHN per month. Targeted neonatal echocardiography (TnECHO) was practised in 80% of the units. Most common management strategies being followed were pulmonary vasodilators (88.1%), inotropes (85.6%), conventional ventilation (68.6%) and high frequency ventilation (59.3%). The most preferred pulmonary vasodilator was sildenafil (79%) and inotropic agent was milrinone (32%). Only 25% of respondents reported use of iNO. None of the participating units used extracorporeal membrane oxygenation. Conclusion We found wide variability in management practices of PPHN across Indian NICUs. Non-selective pulmonary vasodilators are more widely used than iNO. There is an urgent need for structured TnECHO training programs and evidence based national guidelines for standardized management of PPHN as per availability of resources in India. Additional research on low cost alternative therapies to iNO in Indian settings might be helpful.

Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart disease with an incidence of 1%–3% of all congenital heart disease patients. The pulmonary veins returning oxygenated blood from the lungs are draining into the right side (right atrium or great veins), causing systemic hypoxia and cyanosis. TAPVC patients are mostly present at an early stage and need surgical correction to sustain life and prevent complications. However, some subsets of patients with TAPVC in whom the mixing of blood is happening may progress into adult life and have associated pulmonary arterial hypertension (PAH) and right ventricular (RV) dysfunction. We report a case of a young adult lady who presented to our hospital at 16 years of age with TAPVC along with severe PAH and RV dysfunction. During the perioperative period, the patient was successfully managed with pulmonary vasodilators and inotropic support. The objective of the case report was to describe the management strategy followed in the successful treatment of the patient. Due to congestive heart failure, low cardiac output status, and other factors, these individuals will also experience comorbidities such as PAH, RV dysfunction, and organ dysfunction. Patients require care in an environment that has experience handling a variety of problems and a PAH crisis. PAH can be controlled with the aid of pulmonary vasodilators such as sildenafil, bosentan, milrinone, NTG, and inhaled nitric oxide. Mechanical hyperventilation to lower pulmonary vascular resistance will also aid in treatment. When combined with intraoperative transesophageal echocardiography monitoring, the balanced anesthetic method can be used to successfully manage the majority of cases.

Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart disease with an incidence of 1%-3% of all congenital heart disease patients. The pulmonary veins returning oxygenated blood from the lungs are draining into the right side (right atrium or great veins), causing systemic hypoxia and cyanosis. TAPVC patients are mostly present at an early stage and need surgical correction to sustain life and prevent complications. However, some subsets of patients with TAPVC in whom the mixing of blood is happening may progress into adult life and have associated pulmonary arterial hypertension (PAH) and right ventricular (RV) dysfunction. We report a case of a young adult lady who presented to our hospital at 16 years of age with TAPVC along with severe PAH and RV dysfunction. During the perioperative period, the patient was successfully managed with pulmonary vasodilators and inotropic support. The objective of the case report was to describe the management strategy followed in the successful treatment of the patient. Due to congestive heart failure, low cardiac output status, and other factors, these individuals will also experience comorbidities such as PAH, RV dysfunction, and organ dysfunction. Patients require care in an environment that has experience handling a variety of problems and a PAH crisis. PAH can be controlled with the aid of pulmonary vasodilators such as sildenafil, bosentan, milrinone, NTG, and inhaled nitric oxide. Mechanical hyperventilation to lower pulmonary vascular resistance will also aid in treatment. When combined with intraoperative transesophageal echocardiography monitoring, the balanced anesthetic method can be used to successfully manage the majority of cases. [ABSTRACT FROM AUTHOR]

BACKGROUND: The purpose of this study was to compare the outcomes of infants with giant omphalocele (GO) born in two different epochs over two decades at a single institution. Specifically, it examined whether the utilization of selective pulmonary vasodilators and extracorporeal membrane oxygenator (ECMO) in the management of pulmonary hypertension in the second epoch were associated with improved outcomes. METHODS: The medical records of all patients diagnosed with GO at a large children's hospital from January 1, 1996 to December 31, 2016 were reviewed and divided into two epochs. Patients were classified as having an isolated GO or GO with minor or major associated anomalies. GO was defined as a defect more than or equal to 5 cm in size and/or liver in the sac. RESULTS: During the study period, 59 infants with GO were identified. The duration of invasive mechanical ventilation was significantly shorter among the survivors from the second epoch (p = 0.03), with none greater than seven days. There were no significant differences in the outcomes of survival to NICU discharge and length of stay (LOS) between infants in the two epochs. CONCLUSIONS: Infants with GO who required invasive mechanical ventilation for more than seven days did not survive in the second epoch. Survival did not improve with use of selective pulmonary vasodilators and ECMO. This information could be shared with families during prenatal and postnatal counselling to facilitate informed decision making regarding goals of care. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a common hematological malignancy resulting from clonal proliferation of plasma cells and is defined by criteria set forth by the international myeloma working group. Pulmonary hypertension (PH) is defined by an elevated mean pulmonary artery pressure >20mmHg measured during right heart catheterization. Echocardiography-diagnosed PH is relatively common in patients with MM and has been associated with increased mortality, morbidity, and poor stem cell transplant outcomes. PH in patients with MM (PH-MM) is usually multifactorial in origin. MM disease-specific factors, host comorbidities, and treatment-related adverse effects are the key factors for the development of PH-MM. Pragmatically, patients with PH-MM can be grouped into either (i) PH in patients with a new diagnosis of MM or (ii) PH that develops or worsens along the way of MM treatment. In the latter group, drug-induced PH, venous thromboembolism, pulmonary veno occlusive disease, and cardiotoxicity should be considered as possible causes. PH-MM should be evaluated and managed in a multidisciplinary setting. Select individuals with PH-MM could be considered for pulmonary vasodilators at PH-specialized centers. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension secondary to congenital heart diseases is a subset of patients who need pulmonary vasodilators (PVDs). We are reporting an adult female who continued to have severe pulmonary hypertension after corrective surgery for the atrial septal defect. She showed improvement in symptoms and effort tolerance assessed by 6-min walk distance, but on cessation of therapy, showed worsening of exercise tolerance which improved after reintroduction. This report stresses the importance of the need for long-term combination of PVDs without interruption.

Background: Persistent pulmonary hypertension of the newborn (PPHN) is a common neonatal condition associated with significant morbidity and mortality. First-line diagnostic and treatment options such as echocardiography and inhaled nitric oxide (iNO) are not routinely available in resource limited settings and alternative treatment modalities need to be utilized. This study was conducted to assess current diagnostic and management strategies used for PPHN in Indian neonatal intensive care units (NICUs). Methods: A questionnaire in multiple choice question format was sent to practising neonatologists in India via an online survey tool between July to August 2021. Information pertaining to demographic data, diagnostic criteria and management strategies of PPHN was requested. The responses were collated and information processed. Results: There were 118 respondent NICUs (response rate 74%). The majority of neonatal units (65%) admitted an average of 1–3 patients of PPHN per month. Targeted neonatal echocardiography (TnECHO) was practised in 80% of the units. Most common management strategies being followed were pulmonary vasodilators (88.1%), inotropes (85.6%), conventional ventilation (68.6%) and high frequency ventilation (59.3%). The most preferred pulmonary vasodilator was sildenafil (79%) and inotropic agent was milrinone (32%). Only 25% of respondents reported use of iNO. None of the participating units used extracorporeal membrane oxygenation. Conclusion: We found wide variability in management practices of PPHN across Indian NICUs. Non-selective pulmonary vasodilators are more widely used than iNO. There is an urgent need for structured TnECHO training programs and evidence based national guidelines for standardized management of PPHN as per availability of resources in India. Additional research on low cost alternative therapies to iNO in Indian settings might be helpful. [ABSTRACT FROM AUTHOR]

We evaluated pressure‐based right ventricular ejection fraction (RVEF) and diastolic isovolumetric relaxation time constant (Tau) from continuously (up to 30 days) invasive measured right ventricular pressures in mechanically ventilated patients with severe COVID‐19 acute respiratory distress syndrome (ARDS). We retrospectively calculated beat‐to‐beat ejection fraction from right ventricular pressures and dp/dt maximum and minimum in 39 patients treated between October 1st, 2020 and June 30th, 2021. After performing a stepwise logistic regression with survival as a dependent variable, we divided the patients into survivors and nonsurvivors based on their 60‐day mortality. Independent outcome variables were the values of RVEF and Tau over time after insertion of the right ventricular probe along with right ventricular systolic and diastolic pressures (RVSP) and the estimated pulmonary artery diastolic pressure (ePAD). RVEF increased significantly over time in the survivors (estimate: 0.354; 95% confidence interval, CI: 0.18–0.53; p < 0.001) but remained unchanged in the nonsurvivors. Tau increased significantly in the nonsurvivors (estimate: 0.001; 95% CI: 0.0004–0.0018; p < 0.002) but not in the survivors. On the last measurement day, RVSP and ePAD were significantly lower while RVEF was significantly higher in the survivors compared to the nonsurvivors. In COVID‐19 ARDS patient's, calculation of beat‐to‐beat RVEF and Tau from continuously invasive measured right ventricular pressures seems to unravel contrary trends in RVEF with an increase in the surviving and a decrease in the nonsurviving patients. Tau remained unchanged in the surviving but increased in the nonsurviving patients over time. [ABSTRACT FROM AUTHOR]

Abstract Multiple myeloma (MM) is a common hematological malignancy resulting from clonal proliferation of plasma cells and is defined by criteria set forth by the international myeloma working group. Pulmonary hypertension (PH) is defined by an elevated mean pulmonary artery pressure >20 mmHg measured during right heart catheterization. Echocardiography‐diagnosed PH is relatively common in patients with MM and has been associated with increased mortality, morbidity, and poor stem cell transplant outcomes. PH in patients with MM (PH‐MM) is usually multifactorial in origin. MM disease‐specific factors, host comorbidities, and treatment‐related adverse effects are the key factors for the development of PH‐MM. Pragmatically, patients with PH‐MM can be grouped into either (i) PH in patients with a new diagnosis of MM or (ii) PH that develops or worsens along the way of MM treatment. In the latter group, drug‐induced PH, venous thromboembolism, pulmonary veno occlusive disease, and cardiotoxicity should be considered as possible causes. PH‐MM should be evaluated and managed in a multidisciplinary setting. Select individuals with PH‐MM could be considered for pulmonary vasodilators at PH‐specialized centers.

Pulmonary arterial hypertension (PAH) is a rare heterogeneous disorder in the paediatric population which is mostly associated with congenital heart disease. The management of paediatric idiopathic PAH (IPAH) is difficult due to insufficient comparative data and depends on the results of evidence-based adult studies with several pulmonary vasodilators, as well as the clinical experiences of paediatric experts. Our aim was to present the case of a 9-year-old girl who underwent several methods of treatment, including pharmacotherapy with a significant reaction to treprostinil, as well as bilateral lung transplantation. The patient’s treatment was distinguished by the fact that the dose escalation was as rapid as that observed in the adult population. Due to the limited current evidence and knowledge, the initiation of treatment for these patients remains an individual choice. On the grounds of the number of non-specific symptoms, the diagnosis of this patient was a long process and based mainly on the differential diagnosis. The purpose of this paper is to study this example in order to highlight the importance of early symptoms and the quick implementation of intensive treatment. The applied methods may be useful in doubtful diagnosis processes and treatment procedures in the paediatric population.

Abstract We evaluated pressure‐based right ventricular ejection fraction (RVEF) and diastolic isovolumetric relaxation time constant (Tau) from continuously (up to 30 days) invasive measured right ventricular pressures in mechanically ventilated patients with severe COVID‐19 acute respiratory distress syndrome (ARDS). We retrospectively calculated beat‐to‐beat ejection fraction from right ventricular pressures and dp/dt maximum and minimum in 39 patients treated between October 1st, 2020 and June 30th, 2021. After performing a stepwise logistic regression with survival as a dependent variable, we divided the patients into survivors and nonsurvivors based on their 60‐day mortality. Independent outcome variables were the values of RVEF and Tau over time after insertion of the right ventricular probe along with right ventricular systolic and diastolic pressures (RVSP) and the estimated pulmonary artery diastolic pressure (ePAD). RVEF increased significantly over time in the survivors (estimate: 0.354; 95% confidence interval, CI: 0.18–0.53; p

Irreversible pulmonary arterial hypertension is considered a contraindication for surgical or percutaneous closure of atrial septal defects (ASD) due to risk of right heart failure. We present a case of 37 years-old woman who was referred to our center due to progressive worsening fatigue and high probability of pulmonary hypertension on a transthoracic echocardiogram. The diagnostic work-up revealed the presence of an ostium secundum atrial septal defect and severe pre-capillary pulmonary hypertension on right heart cathetherization (RHC). The patient was considered inoperable and started medical therapy with sildenafil and bosentan. After one year of treatment, she repeated RHC that showed a significant reduction in pulmonary vascular resistance making her eligible for closure. Surgical closure of ASD with a fenestra was performed with success. Our case emphasizes the importance of individual assessment even if cases where initial evaluation is unfavorable to closure in accordance with the guidelines. [ABSTRACT FROM AUTHOR]

Left ventricular assist devices (LVADs) are increasingly utilized for patients with end-stage heart failure (HF). Pulmonary hypertension (PH) is highly prevalent in this patient population mainly due to prolonged left ventricular (LV) failure and chronically elevated filling pressures. The effect of LVADs on pulmonary circulation and right ventricular (RV) function has recently become an area of great attention in literature. PH can lead to post-LVAD right ventricular failure (RVF) that confers a high risk of morbidity and mortality. Multiple pulmonary vasodilators, that are primarily used for the treatment of pulmonary arterial hypertension (PAH), have been studied for the treatment of PH after LVAD implantation, and some of them have shown promising results. This review aims to investigate the treatment options for PH in patients on LVADs, as well as to give an overview about the pathophysiology of PH and RVF in these patients. [ABSTRACT FROM AUTHOR]

There are limited data regarding the feasibility of transitioning from intravenous prostacyclins to selexipag in pulmonary arterial hypertension patients. We present a case series of successful transitions from intravenous prostacyclins to selexipag in the majority of carefully selected five stable pulmonary arterial hypertension patients using a standardized protocol in the outpatient setting.

Background: There have been over 200 million cases and 4.4 million deaths from COVID-19 worldwide. Despite the lack of robust evidence one potential treatment for COVID-19 associated severe hypoxaemia is inhaled pulmonary vasodilator (IPVD) therapy, using either nitric oxide (iNO) or prostaglandins. We describe the implementation of, and outcomes from, a protocol using IPVDs in a cohort of patients with severe COVID-19 associated respiratory failure receiving maximal conventional support. Methods: Prospectively collected data from adult patients with SARS-CoV-2 admitted to the intensive care unit (ICU) at a large teaching hospital were analysed for the period 14th March 2020 - 11th February 2021. An IPVD was considered if the PaO2/FiO2 (PF) ratio was less than 13.3kPa despite maximal conventional therapy. Nitric oxide was commenced at 20ppm and titrated to response. If oxygenation improved Iloprost nebulisers were commenced and iNO weaned. The primary outcome was percentage changes in PF ratio and Alveolar-arterial (A-a) gradient. Results: Fifty-nine patients received IPVD therapy during the study period. The median PF ratio before IPVD therapy was commenced was 11.33kPa (9.93-12.91). Patients receiving an IPVD had a lower PF ratio (14.37 vs. 16.37kPa, p = 0.002) and higher APACHE-II score (17 vs. 13, p = 0.028) at ICU admission. At 72 hours after initiating an IPVD the median improvement in PF ratio was 33.9% (-4.3-84.1). At 72 hours changes in PF ratio (70.8 vs. -4.1%, p< 0.001) and reduction in A-a gradient (44.7 vs. 14.8%, p< 0.001) differed significantly between survivors (n = 33) and non-survivors (n = 26). Conclusions: The response to IPVDs in patients with COVID-19 associated acute hypoxic respiratory failure differed significantly between survivors and non-survivors. Both iNO and prostaglandins may offer therapeutic options for patients with severe refractory hypoxaemia due to COVID-19. The use of inhaled prostaglandins, and iNO where feasible, should be studied in adequately powered prospective randomised trials. [ABSTRACT FROM AUTHOR]

Medical therapy in chronic thromboembolic pulmonary hypertension (CTEPH) has two primary goals- to prevent recurrent thromboembolic events and to reduce right ventricular afterload with targeted medications (vasodilators) for pulmonary hypertension. These medical strategies are used in conjunction with mechanical treatments for CTEPH (pulmonary thromboendarterectomy (PTE) or balloon angioplasty). In the context of this review, we discuss anticoagulation strategies, patient selection for vasodilator therapy with particular focus on hemodynamic and clinically meaningful definitions of residual pulmonary hypertension after PTE and inoperable disease and then summarize the current randomized clinical trials (RCT) which have studied effectiveness of vasodilators in patients with CTEPH. [ABSTRACT FROM AUTHOR]

Fibrosing mediastinitis (FM) is a heterogeneous disease characterized by sclerosing fibrosis of mediastinal structures. Pulmonary hypertension (PH) may complicate the course of the disease and can contribute significantly to the morbidity of FM. Due to the rarity and complexity of the disease, evidence-based guidelines are not currently available, and the optimal treatment approach is unknown. Management approaches should be individualized, and current techniques are often unsatisfactory. Here, we present two cases of PH complicating FM that were managed using pulmonary artery vasodilator therapy with excellent hemodynamic response. [ABSTRACT FROM AUTHOR]

In newborns with congenital diaphragmatic hernia (CDH), the mediastinal shift caused by the herniated organs negatively affects lung development. Assessment of the fetal magnetic resonance imaging (MRI) mediastinal shift angle (MSA) was shown to have an inverse correlation with the total fetal lung volume (TFLV), being associated with neonatal survival. However, a possible association with postnatal morbidity has never been investigated. We hypothesize that the degree of the mediastinal shift could be associated with higher respiratory and cardiocirculatory impairment, requiring intensive treatments and extended hospitalization in survivors. We retrospectively consider a cohort of isolated, left-sided CDH, for whom we calculated the MSA and the observed/expected (O/E) TFLV at fetal MRI. We performed a data collection regarding inotropic or vasoactive support, treatment with pulmonary vasodilators, mechanical ventilation, and length of stay. General linear models were performed. The MSA and O/E TFLV were inversely correlated (Pearson's coefficient − 0.65, p < 0.001), and deceased patients showed higher MSA values then survivors (p = 0.011). Among survivors, an increase in MSA was associated with longer pharmacological treatments (dobutamine: p = 0.016; dopamine: p = 0.049; hydrocortisone: p = 0.003; nitric oxide: p = 0.002; sildenafil: p = 0.039; milrinone: p = 0.039; oxygen: p = 0.066), and mechanical ventilation (p = 0.005), with an increasing trend in the length of hospitalization (p = 0.089). Conclusion: The MSA indirectly reflects lung hypoplasia and is associated with a higher neonatal intensity of cares. However, further studies are needed to consolidate the results. Trial registration: The study is an exploratory post hoc analysis of the registered NeoAPACHE protocol at ClinicalTrials.gov with the identifier NCT04396028. What is Known: • In congenital diaphragmatic hernia, the lung size, liver position, and defect side are the most common prenatal prognostic parameters used in clinical practice for morbidity and mortality prediction. • Lung hypoplasia, strictly associated with lung size, is estimated by observed/expected lung to head ratio and observed/expected total fetal lung volume with prenatal ultrasound and fetal magnetic resonance imaging, respectively. What is New: • A new, faster, more straightforward, and less operator-dependent tool to assess CDH severity could be the mediastinal shift angle calculation with fetal magnetic resonance imaging. • Postnatal clinical severity, considered as a postnatal cardiovascular and respiratory impairment that indirectly reflects lung hypoplasia, is associated with an increased mediastinal shift angle calculation. [ABSTRACT FROM AUTHOR]

• Clinical phenotypes of PAH in adult CHD patients are associated with prognosis. • In this real-world study cohort, PAH-specific therapy has a low impact on mortality. • In advanced NYHA functional class combination therapy significantly improves exercise capacity. • Advanced stage of the disease at initiation of treatment involves a high risk of death. Mortality of pulmonary hypertension associated with congenital heart disease (PAH-CHD) in adults remains high. To identify predictors of death and to assess the impact of treatment on outcome. Retrospective, multicenter cohort study of 103 adults with PAH-CHD followed-up for 8.6 ± 4.6 years. Patients were grouped according to underlying shunt type into pre-tricuspid, post-tricuspid and complex. Survival rates were analyzed and predictors of death were investigated with Cox regression models. In the post-tricuspid and complex groups (38 and 37 patients, respectively), the most common clinical PAH-CHD subgroup was Eisenmenger syndrome (76.3% and 59.5%, respectively) whereas, in the pre-tricuspid group (28 patients), 46.5% of patients had small or corrected defects. Overall, 88 patients received vasodilators; 39% required combination-therapy. Overall survival at 10 years was 65%. Mortality was highest in the pre-tricuspid group, FC-III-IV and amongst patients receiving monotherapy (p < 0.050). On multivariate analysis, predictors of poor outcome were pericardial effusion (HR: 4,520 [1,470–13,890]; p = 0,008), oxygen saturation(HR: 0.940 [0,900 - 0,990]; p = 0,018) and genetic syndromes(HR: 3,280 [1,098–9,780]; p = 0,033). Patients in advanced stages at initiation of treatment were at high risk of death and strong consideration should be given for more aggressive therapy. [ABSTRACT FROM AUTHOR]

In this review, two cases of severe pulmonary hypertension of different classes that have been successfully treated using inhaled nitroglycerine are presented. In a community hospital setting and in cases of life-threatening right heart failure and shock not responding to simple traditional treatments, thought should be given to the use of inhaled nitroglycerine. Inhaled nitroglycerine is practical, cheap, and readily available in any hospital without reconstitution. This approach may allow for the treatment, or at least temporary stabilisation, of these patients until transferred to a tertiary care facility.

Chronic thromboembolic pulmonary hypertension (CTEPH) is part of group 4 of the pulmonary hypertension (PH) classification and generally affects more than a third of patients referred to PH centers. It is a three-compartment disease involving proximal (lobar-to-segmental) and distal (subsegmental) pulmonary arteries that are obstructed by persistent fibrothrombotic material, and precapillary pulmonary arteries that can be affected as in pulmonary arterial hypertension. It is a rare complication of pulmonary embolism (PE), with an incidence of around 3% in PE survivors. The observed incidence of CTEPH in the general population is around six cases per million but could be three times higher than this, as estimated from PE incidence. However, a previous venous thromboembolic episode is not always documented. With advances in multimodality imaging and therapeutic management, survival for CTEPH has improved for both operable and inoperable patients. Advanced imaging with pulmonary angiography helps distinguish proximal from distal obstructive disease. However, right heart catheterization is of utmost importance to establish the diagnosis and hemodynamic severity of PH. The therapeutic strategy relies on a stepwise approach, starting with an operability assessment. Pulmonary endarterectomy (PEA), also known as pulmonary thromboendarterectomy, is the first-line treatment for operable patients. Growing experience and advances in surgical technique have enabled expansion of the distal limits of PEA and significant improvements in perioperative and mid- to long-term mortality. In patients who are inoperable or who have persistent/recurrent PH after PEA, medical therapy and/or balloon pulmonary angioplasty (BPA) are effective treatment options with favorable outcomes that are increasingly used. All treatment decisions should be made with a multidisciplinary team that includes a PEA surgeon, a BPA expert, and a chest radiologist., (Copyright © 2024 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Despite significant advances in understanding acute respiratory distress syndrome (ARDS), mortality rates remain high. The appropriate use of adjunctive therapies can improve outcomes, particularly for patients with moderate to severe hypoxia. In this review, the authors discuss the evidence basis behind prone positioning, recruitment maneuvers, neuromuscular blocking agents, corticosteroids, pulmonary vasodilators, and extracorporeal membrane oxygenation and considerations for their use in individual patients and specific clinical scenarios. Because the heterogeneity of ARDS poses challenges in finding universally effective treatments, an individualized approach and continued research efforts are crucial for optimizing the utilization of adjunctive therapies and improving patient outcomes., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Left ventricular assist devices (LVADs) are increasingly utilized for patients with end-stage heart failure (HF). Pulmonary hypertension (PH) is highly prevalent in this patient population mainly due to prolonged left ventricular (LV) failure and chronically elevated filling pressures. The effect of LVADs on pulmonary circulation and right ventricular (RV) function has recently become an area of great attention in literature. PH can lead to post-LVAD right ventricular failure (RVF) that confers a high risk of morbidity and mortality. Multiple pulmonary vasodilators, that are primarily used for the treatment of pulmonary arterial hypertension (PAH), have been studied for the treatment of PH after LVAD implantation, and some of them have shown promising results. This review aims to investigate the treatment options for PH in patients on LVADs, as well as to give an overview about the pathophysiology of PH and RVF in these patients.

Background: We performed a meta-analysis to evaluate the efficacy and safety of pulmonary vasodilators in pediatric pulmonary hypertension (PH) patients.Methods: We searched electronic databases including PubMed, EMBASE, and the Cochrane Library up to May 2020, and conducted a subgroup analysis for pulmonary vasodilators or underlying disease.Results: Fifteen studies with 719 pediatric PH patients were included in the meta-analysis. Adverse events did not differ (p = 0.11, I2 = 15%) between the pulmonary vasodilators group and the control group, neither in the subgroups. In total, compared with the control group treatment, pulmonary vasodilators significantly decreased the mortality (p = 0.002), mean pulmonary artery pressure (mPAP, p = 0.02), and mechanical ventilation duration (p = 0.03), also improved the oxygenation index (OI, p = 0.01). In the persistent pulmonary hypertension of the newborn (PPHN) subgroup, phosphodiesterase type 5 inhibitors (PDE5i) significantly reduced mortality (p = 0.03), OI (p = 0.007) and mechanical ventilation duration (p = 0.004). Administration of endothelin receptor antagonists (ERAs) improved OI (p = 0.04) and mechanical ventilation duration (p < 0.00001) in PPHN. We also found that in the pediatric pulmonary arterial hypertension (PPAH) subgroup, mPAP was pronouncedly declined with ERAs (p = 0.006). Systolic pulmonary artery pressure (sPAP, p < 0.0001) and pulmonary arterial/aortic pressure (PA/AO, p < 0.00001) were significantly relieved with PDE5i, partial pressure of arterial oxygen (PaO2) was improved with prostacyclin in postoperative PH (POPH) subgroup (p = 0.001). Compared with the control group, pulmonary vasodilators could significantly decrease PA/AO pressure (p < 0.00001) and OI (p < 0.00001) in the short-term (duration 30 days).Conclusion: Pulmonary vasodilators decrease the mortality in pediatric PH patients, improve the respiratory and hemodynamic parameters, reduce the mechanical ventilation duration.

Pulmonary veno-occlusive disease (PVOD) is a rare but devastating cause of pulmonary hypertension (PH) characterized by preferential remodeling of the pulmonary venules.Mitomycin-C (MMC) is an alkylating agent commonly used in chemotherapy with documented lung toxicity as well as PVOD adverse effect. The incidence of PVOD in patients with anal cancer is much higher than in those with idiopathic PVOD, especially following treatment with MMC. An accurate diagnosis of PVOD can be made based on noninvasive investigations utilizing oxygen parameters, low diffusing capacity for carbon monoxide and characteristic signs on high-resolution computed tomography of the chest. No evidence-based medical therapy exists for PVOD at present and lung transplant remains the preferred definitive therapy for eligible patients. We present a case of autopsy confirmed MMC induced PVOD in a patient with metastatic anal cancer.

Persistent pulmonary hypertension of the newborn (PPHN) is one of the main causes of neonatal morbidity and mortality. It is characterized by sustained elevation of pulmonary vascular resistance (PVR), preventing an increase in pulmonary blood flow after birth. The affected neonates fail to establish blood oxygenation, precipitating severe respiratory distress, hypoxemia, and eventually death. Inhaled nitric oxide (iNO), the only approved pulmonary vasodilator for PPHN, constitutes, alongside supportive therapy, the basis of its treatment. However, nearly 40% of infants are iNO resistant. The cornerstones of increased PVR in PPHN are pulmonary vasoconstriction and vascular remodeling. A better understanding of PPHN pathophysiology may enlighten targeted and more effective therapies. Sildenafil, prostaglandins, milrinone, and bosentan, acting as vasodilators, besides glucocorticoids, playing a role on reducing inflammation, have all shown potential beneficial effects on newborns with PPHN. Furthermore, experimental evidence in PPHN animal models supports prospective use of emergent therapies, such as soluble guanylyl cyclase (sGC) activators/stimulators, l-citrulline, Rho-kinase inhibitors, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists, recombinant superoxide dismutase (rhSOD), tetrahydrobiopterin (BH4) analogs, ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs), 5-HT2A receptor antagonists, and recombinant human vascular endothelial growth factor (rhVEGF). This review focuses on current knowledge on alternative and novel pathways involved in PPHN pathogenesis, as well as recent progress regarding experimental and clinical evidence on potential therapeutic approaches for PPHN.

Mixed connective tissue disease (MCTD) involves various clinical manifestations, and pulmonary hypertension (PH) is an important organ dysfunction defining the prognosis of MCTD. The pathology of PH is heterogeneous. Here, we present 2 cases of MCTD complicated by PH that had contrasting clinical courses. The first case involved a 54-year-old woman with Raynaud's phenomenon and dyspnoea on exertion. She was diagnosed with MCTD accompanied by pulmonary arterial hypertension (PAH) and was treated with ambrisentan and tadalafil in addition to high-dose glucocorticoid (GC) therapy and rituximab therapy. After treatment, her PH resolved. The second case involved a 64-year-old woman with Raynaud's phenomenon and dyspnoea on exertion. She was similarly diagnosed with MCTD accompanied by PAH and was treated with ambrisentan and tadalafil in addition to high-dose GC therapy and cyclophosphamide pulse therapy. However, she showed exacerbation of her respiratory condition and manifestation of pulmonary veno-occlusive disease (PVOD). Thus, the treatment was discontinued, and subsequently, her condition improved and eventually returned to that before treatment. The findings suggest that the presence or absence of latent PVOD might be an important factor for predicting the therapeutic responsiveness of MCTD-associated PH. Evaluation of chest radiography findings, computed tomography findings, percent vital capacity, and percent carbon monoxide diffusion capacity might be useful for predicting prognosis and might aid in treatment. PVOD could be underlying in patients with CTD-PH. When the complication of PVOD is suggested by chest CT or pulmonary function test, we need a careful introduction with pulmonary vasodilators. So, combination therapy of pulmonary vasodilators should not be applied in all patients with CTD-PH since underlying PVOD could deteriorate the patient's condition. [ABSTRACT FROM AUTHOR]

In heart transplantation, pulmonary hypertension and increased pulmonary vascular resistance followed by donor right ventricular dysfunction remain a major cause of perioperative morbidity and mortality. In lung transplantation, primary graft dysfunction remains a major obstacle because it can cause bronchiolitis obliterans and mortality. Pulmonary vasodilators have been used as an adjunct therapy for heart or lung transplantation, mainly to treat pulmonary hypertension, right ventricular failure, and associated refractory hypoxemia. Among pulmonary vasodilators, inhaled nitric oxide is unique in that it is selective in pulmonary circulation and causes fewer systemic complications such as hypotension, flushing, or coagulopathy. Nitric oxide is expected to prevent or attenuate primary graft dysfunction by decreasing ischemia-reperfusion injury in lung transplantation. However, when considering the long-term benefit of these medications, little evidence supports their use in heart or lung transplantation. Current guidelines endorse inhaled vasodilators for managing immediate postoperative right ventricular failure in lung or heart transplantation, but no guidance is offered regarding agent selection, dosing, or administration. This review presents the current evidence of inhaled nitric oxide in lung or heart transplantation as well as comparisons with other pulmonary vasodilators including cost differences in consideration of economic pressures to contain rising pharmacy costs. [ABSTRACT FROM AUTHOR]

The present article reports three clinical cases in order to elucidate the diversity of the pathophysiological mechanisms that underlie rheumatoid arthritis associated pulmonary hypertension. The condition's three major causes are: interstitial lung disease, vasculitis, and chronic thromboembolic disease, but it should be noted that the multiple pulmonary manifestations of rheumatoid arthritis, can all contribute to chronic lung disease or hypoxia. The first patient in this report suffered from moderate restriction due to fibrosis and was diagnosed with pulmonary hypertension during an episode of life threatening hypoxia. Early upfront combination therapy prevented intubation and reversed hypoxia to adequate levels. The second presented patient was a case of isolated pulmonary hypertension attributable to vasculopathy. The patient maintained normal lung volumes but low diffusion capacity and echocardiography dictated the need for right heart catheterization. Finally, the third patient presented severe functional limitation due to several manifestations of rheumatoid arthritis, but a past episode of acute pulmonary embolism was also reported although it had never been evaluated. Chronic thromboembolic disease was eventually proved to be one major cause of the patient's pulmonary hypertension. The importance of early identification of pulmonary hypertension in patients with rheumatoid arthritis is therefore emphasized, especially since multiple treatment options are available, symptoms can be treated, and right heart failure can be avoided.

Treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) have recently evolved with the availability of balloon pulmonary angioplasty (BPA) and pulmonary vasodilators. Our aim was to analyze the prognostic variables associated with long-term outcome in a cohort of patients with not-operated CTEPH. From January 2006 to December 2016, 343 newly diagnosed consecutive patients with not-operated CTEPH were diagnosed and followed up in the French Reference Center for Pulmonary Hypertension. Overall long-term survival and prognostic factors according to the diagnosis period (early period, 2006–2012, vs recent period, since 2013, i.e., one year before availability of BPA) were analyzed. In the overall population, baseline New York Heart Association functional class, right atrial pressure, 6-minute walk distance (6MWD), and diagnosis period were independent predictors of survival. The 1- and 3-year survival rates of patients diagnosed in the recent period (n = 170) were 91.6% and 85.0%, compared with 89.0% and 74.3% in patients diagnosed in the early period (n = 173), respectively (p = 0.030). Multivariate analysis from patients diagnosed in the recent period found that baseline 6MWD (per 20 m increase in distance) (hazard ratio [HR], 0.879; 95% confidence interval [CI], 0.832–0.928, p < 0.001) and BPA (HR, 0.307; 95% CI, 0.099–0.957; p = 0.042) were independently associated with survival. Survival of not-operated patients with CTEPH has significantly improved in the recent management era. New treatment options, including BPA, might have the potential to improve the prognosis of patients with inoperable CTEPH. [ABSTRACT FROM AUTHOR]