Use Of Pulmonary Vasodilators Research Articles

Multiple coronary artery microfistulae are common and progress in adult patients late after Fontan operation

Abstract Background Coronary angiograms of adult Fontan patients sometimes show the abnormal multiple coronary artery microfistulae (mCAFs) that drain directly into the ventricular chamber. They look like coronary artery fistulae or Thebesian vein. Angiographically detectable mCAFs are a rare finding sometimes associated with myocardial ischemia due to coronary steal and volume overload of ventricles in non-CHD adults. However, there are limited data concerning these mCAFs in the setting of CHD patients. Purpose The aim of this study is to demonstrate presence, character, and changes with growth of mCAFs in adult patients late after Fontan operation. Methods This study is single-center retrospective review of adults (16 years old or older) with Fontan circulation patients who had undergone cardiac catheterization for routine Fontan surveillance between 2009-2022. We assessed the presence of angiographically detectable mCAFs from ascending aortography. After identification of the characteristic cases, we examined the ventricular morphology, the portion of drainage, and compared with previous findings of angiograms. SaO2, EF of main ventricle, CVP, EDP of main ventricle, BNP, and use of pulmonary vasodilators were compared between mCAFs(+) group and mCAFs(-) group. We also reviewed clinical manifestation and findings of exercise stress ECG of the patients. Pulmonary atresia with intact ventricular septum was excluded because abnormal coronary arterial communications have been well documented in this condition. Results Among 90 Fontan patients who had undergone catheterization, significant mCAFs were observed in a total of 18 cases (20%). There were 10 right-dominant single ventricle, 4 left-dominant single ventricle, and 4 unbalanced two ventricles. In all cases, including left-dominant single ventricle, all fistulae drained into right ventricle cavity, never into left ventricle. The patients who underwent serial catheterizations demonstrated that the dilation and tortuosity of fistulae progressed over time. The comparison of two groups showed SaO2 was low, BNP and CVP was high significantly in mCAFs(+) group. There were no significant differences in other factors including age at catheterization and the use of pulmonary vasodilators. Among 10 patients who had underwent exercise stress ECG, only 1 patient showed ST segment depression. None had clinical history of chest pain, and arrhythmia, and ischemic event. Conclusions MCAFs are common and progress in adult patients late after Fontan operation. Although the clinical significance and etiology of these findings remains uncertain, particular attention should be given to subclinical Fontan failure caused by hhigh CVP, volume overload, and myocardial ischemia for the future of adult Fontan patients who have prominent mCAFs.

Pediatric Pulmonary Hypertension in Left-Sided Heart Disease

Pulmonary hypertension (PH) from left-sided heart disease (group-II PH) is an increasingly recognized cause of PH in pediatrics. Group-II PH can result from obstruction at any level of the left heart, and can progress over time. Management can be particularly difficult, as targeted PH therapy in the setting of a fixed obstruction carries a risk of pulmonary vascular congestion and pulmonary edema. Based on existing evidence, the use of pulmonary vasodilators in group II PH is not recommended, and management centers around early identification and correction of the underlying left-sided lesion. In this review, we highlight the pathophysiology of group-II PH, the diagnostic evaluation of left heart pathology, and a general approach to both medical and surgical management, with particular attention to relevant left-sided lesions. Group-II PH is a multifaceted and progressive disease process that poses a difficult challenge to clinicians, and requires a thoughtful and individualized approach to management.

Current diagnosis and treatment practice for pulmonary hypertension in bronchopulmonary dysplasia-A survey study in Germany (PUsH BPD).

Pulmonary hypertension (PH) is the most severe complication in preterm infants with bronchopulmonary dysplasia (BPD) and associated with significant mortality. Diagnostic and treatment strategies, however, still lack standardization. By the use of a survey study (PH in BPD), we assessed clinical practice (diagnosis, treatment, follow-up) in preterm infants with early postnatal persistent pulmonary hypertension of the newborn(PPHN) as well as at risk for or with established BPD-associated PH between 06/2018 and 10/2020 in two-thirds of all German perinatal centers with >70 very low birthweight infants/year including their cardiology departments and outpatient units. Data wereanalyzed descriptively by measures of locations and distributional shares. In routine postnatal care, clinical presentation and echocardiography were reported as the main diagnostic modalities to screen for PPHN in preterm infants, whereas biomarkers brain natriuretic peptide/N-terminal pro b-type natriuretic peptide were infrequently used. For PPHN treatment, inhaled nitric oxidewas used in varying frequency. The majority of participants agreed to prescribe diuretics and steroids (systemic/inhaled) for infants at risk for or with established BPD-associated PH and strongly agreed on recommending respiratory syncytial virus immunization and the use of home monitoring upon discharge. Reported oxygen saturation targets, however, varied in these patients in in- and outpatient care. The survey reveals shared practices in diagnostic and therapeutic strategies for preterms with PPHN and BPD-associated PH in Germany. Future studies are needed to agree on detailed echo parameters and biomarkers to diagnose and monitor disease next to a much-needed agreement on the use of pulmonary vasodilators, steroids, and diuretics as well as target oxygen saturation levels.

A multidisciplinary approach to severe bronchopulmonary dysplasia is associated with resolution of pulmonary hypertension.

To describe our multidisciplinary bronchopulmonary dysplasia (BPD) consult team's systematic approach to BPD associated pulmonary hypertension (PH), to report our center outcomes, and to evaluate clinical associations with outcomes. Retrospective cohort of 60 patients with BPD-PH who were referred to the Seattle Children's Hospital BPD team from 2018 to 2020. Patients with critical congenital heart disease were excluded. Demographics, comorbidities, treatments, closure of hemodynamically relevant intracardiac shunts, and clinical outcomes including time to BPD-PH resolution were reviewed. Median gestational age of the 60 patients was 25 weeks (IQR: 24-26). 20% were small for gestational age (SGA), 65% were male, and 25% received a tracheostomy. With aggressive cardiopulmonary management including respiratory support optimization, patent ductus arteriosus (PDA) and atrial septal defect (ASD) closure (40% PDA, 5% ASD, 3% both), and limited use of pulmonary vasodilators (8%), all infants demonstrated resolution of PH during the follow-up period, including three (5%) who later died from non-BPD-PH morbidities. Neither SGA status nor the timing of PH diagnosis (<36 vs. ≥36 weeks PMA) impacted the time to BPD-PH resolution in our cohort [median 72 days (IQR 30.5-166.5)]. Our multidisciplinary, systematic approach to BPD-PH management was associated with complete resolution of PH with lower mortality despite less sildenafil use than reported in comparable cohorts. Unique features of our approach included aggressive PDA and ASD device closure and rare initiation of sildenafil only after lack of BPD-PH improvement with respiratory support optimization and diagnostic confirmation by cardiac catheterization.

Worse survival in patients with right ventricular dysfunction and COVID-19–associated acute respiratory distress requiring extracorporeal membrane oxygenation: A multicenter study from the ORACLE Group

ObjectiveWe sought to determine the impact of right ventricular dysfunction on the outcomes of mechanically ventilated patients with COVID-19 requiring veno-venous extracorporeal membrane oxygenation. MethodsSix academic centers conducted a retrospective analysis of mechanically ventilated patients with COVID-19 stratified by support with veno-venous extracorporeal membrane oxygenation during the first wave of the pandemic (March to August 2020). Echocardiograms performed for clinical indications were reviewed for right and left ventricular function. Baseline characteristics, hospitalization characteristics, and survival were compared. ResultsThe cohort included 424 mechanically ventilated patients with COVID-19, 126 of whom were cannulated for veno-venous extracorporeal membrane oxygenation. Right ventricular dysfunction was observed in 38.1% of patients who received extracorporeal membrane oxygenation and 27.4% of patients who did not receive extracorporeal membrane oxygenation with an echocardiogram. Biventricular dysfunction was observed in 5.5% of patients who received extracorporeal membrane oxygenation. Baseline patient characteristics were similar in both the extracorporeal membrane oxygenation and non–extracorporeal membrane oxygenation cohorts stratified by the presence of right ventricular dysfunction. In the extracorporeal membrane oxygenation cohort, right ventricular dysfunction was associated with increased inotrope use (66.7% vs 24.4%, P < .001), bleeding complications (77.1% vs 53.8%, P = .015), and worse survival independent of left ventricular dysfunction (39.6% vs 64.1%, P = .012). There was no significant difference in days ventilated before extracorporeal membrane oxygenation, length of hospital stay, hours on extracorporeal membrane oxygenation, duration of mechanical ventilation, vasopressor use, inhaled pulmonary vasodilator use, infectious complications, clotting complications, or stroke. The cohort without extracorporeal membrane oxygenation cohort demonstrated no statistically significant differences in in-hospital outcomes. ConclusionsThe presence of right ventricular dysfunction in patients with COVID-19–related acute respiratory distress syndrome supported with veno-venous extracorporeal membrane oxygenation was associated with increased in-hospital mortality. Additional studies are required to determine if mitigating right ventricular dysfunction in patients requiring veno-venous extracorporeal membrane oxygenation improves mortality.

Left Heart Disease Phenotype in Elderly Patients with Pulmonary Arterial Hypertension: Insights from the Italian PATRIARCA Registry.

Pulmonary arterial hypertension (PAH) in the elderly is often associated with left heart disease (LHD), prompting concerns about the use of pulmonary vasodilators. The PATRIARCA registry enrolled ≥70 year-old PAH or chronic thromboembolic pulmonary hypertension (CTEPH) patients at 11 Italian centers from 1 December 2019 through 15 September 2022. After excluding those with CTEPH, post-capillary PH at the diagnostic right heart catheterization (RHC), and/or incomplete data, 23 (33%) of a total of 69 subjects met the criteria proposed in the AMBITION trial to suspect LHD. Diabetes [9 (39%) vs. 6 (13%), p = 0.01] and chronic kidney disease [14 (61%) vs. 12 (26%), p = 0.003] were more common, and the last RHC pulmonary artery wedge pressure [14 ± 5 vs. 10 ± 3 mmHg, p < 0.001] was higher and pulmonary vascular resistance [5.56 ± 3.31 vs. 8.30 ± 4.80, p = 0.02] was lower in LHD than non-LHD patients. However, PAH therapy was similar, with 13 (57%) and 23 (50%) subjects, respectively, taking two oral drugs. PAH medication patterns remained comparable between LHD and non-LHD patients also when the former [37, 54%] were identified by atrial fibrillation and echocardiographic features of LHD, in addition to the AMBITION criteria. In this real-world snapshot, elderly PAH patients were treated with pulmonary vasodilators, including combinations, despite a remarkable prevalence of a LHD phenotype.

Selective Use of Pulmonary Vasodilators in Patients with Fontan Physiology.

Fontan-associated liver disease is a well-known sequela following the Fontan procedure for patients living with single-ventricle heart disease. Pulmonary vasodilators, such as phosphodiesterase type 5 inhibitors, have emerged as a potential therapeutic option for lowering central venous pressures by reducing pulmonary vascular resistance. We performed a single-center retrospective review of Fontan patients who were placed on pulmonary vasodilator therapy with prehemodynamic and posthemodynamic, MR elastography, and histologic assessments. A total of 125 patients with Fontan circulation underwent surveillance with cardiac catheterization during the review period. Fifty-three (42%) patients who did not have increased end-diastolic pressures at the time of cardiac catheterization were started on phosphodiesterase type 5 inhibitor therapy. Nine patients (17%) underwent posttherapy follow-up catheterization. The mean Fontan pressure decreased from 15.4 ± 3.3 mmHg to 13.3 ± 2.5 mmHg (p=0.026), after initiation of pulmonary vasodilatory therapy. There was no change in end-diastolic pressure, transpulmonary gradient, wedge pressure, pulmonary vascular resistance, cardiac index, or saturation. Eleven patients (21%) underwent pretherapy MR elastography testing with posttherapy follow-up MR elastography. We found no improvement in liver stiffness score following the application of pulmonary vasodilators. Three patients underwent pretherapy and posttherapy liver biopsies, with variable histological changes observed within the hepatic parenchyma. These data demonstrate indeterminate results for the selective use of pulmonary vasodilators but highlight the need for large prospective randomized control trials of pulmonary vasodilator therapies to fully assess the benefit of such therapies in Fontan-associated liver disease.

Pulmonary Hypertension in Preterm Infants Treated With Laser vs Anti–Vascular Endothelial Growth Factor Therapy for Retinopathy of Prematurity

Anti-vascular endothelial growth factor (VEGF) therapy for retinopathy of prematurity (ROP) has potential ocular and systemic advantages compared with laser, but we believe the systemic risks of anti-VEGF therapy in preterm infants are poorly quantified. To determine whether there was an association with increased risk of pulmonary hypertension (PH) in preterm infants with ROP following treatment with anti-VEGF therapy as compared with laser treatment. This multicenter retrospective cohort study took place at neonatal intensive care units of 48 children's hospitals in the US in the Pediatric Health Information System database from 2010 to 2020. Participants included preterm infants with gestational age at birth 22 0/7 to 31 6/7 weeks who had ROP treated with anti-VEGF therapy or laser photocoagulation. Anti-VEGF therapy vs laser photocoagulation. New receipt of pulmonary vasodilators at least 7 days after ROP therapy was compared between exposure groups, matched using propensity scores generated from preexposure variables, and adjusted for birth year and hospital. The odds of receiving an echocardiogram after 30 days of age was also included to adjust for secular trends and interhospital variation in PH screening. Among 1577 patients (55.9% male) meeting inclusion criteria, 689 received laser photocoagulation and 888 received anti-VEGF treatment (95% bevacizumab, 5% ranibizumab). Patients were first treated for ROP at median 36.4 weeks' postmenstrual age (IQR, 34.6-38.7). A total of 982 patients (491 in each group) were propensity score matched. Good covariate balance was achieved, as indicated by a model variance ratio of 1.15. More infants who received anti-VEGF therapy were treated for PH, but when adjusted for hospital and year, this was no longer statistically significant (6.7%; 95% CI, 2.6-6.9 vs 4.3% 95% CI, 4.4-10.2; adjusted odds ratio, 1.62; 95% CI, 0.90-2.89; P = .10). Anti-VEGF therapy was not associated with greater use of pulmonary vasodilators after adjustment for hospital and year. Our findings suggest exposure to anti-VEGF may be associated with PH, although we cannot exclude the possibility of residual confounding based on systemic comorbidities or hospital variation in practice. Future studies investigating this possible adverse effect seem warranted.

COMMON CLINICAL VARIABLES DO NOT IDENTIFY PATIENTS WITH SCLERODERMA AND EARLY PULMONARY HYPERTENSION

COMMON CLINICAL VARIABLES DO NOT IDENTIFY PATIENTS WITH SCLERODERMA AND EARLY PULMONARY HYPERTENSION

Emerging phenotypes of pulmonary hypertension associated with COPD: a field guide.

Purpose of reviewPulmonary hypertension (PH) is a common complication of chronic obstructive lung disease (COPD), but clinical presentation is variable and not always ’proportional’ to the severity of the obstructive disease. This review aims to analyze heterogeneity in clinical features of PH-COPD, providing a guide for diagnosis and management according to phenotypes.Recent findingsRecent works have focused on severe PH in COPD, providing insights into the characteristics of patients with predominantly vascular disease. The recently recognized ’pulmonary vascular phenotype’, characterized by severe PH and mild airflow obstruction with severe hypoxemia, has markedly worse prognosis and may be a candidate for large trials with pulmonary vasodilators. In severe PH, which might be best described by a pulmonary vascular resistance threshold, there may also be a need to distinguish patients with mild COPD (pulmonary vascular phenotype) from those with severe COPD ('Severe COPD-Severe PH’ phenotype).SummaryCorrect phenotyping is key to appropriate management of PH associated with COPD. The lack of evidence regarding the use of pulmonary vasodilators in PH-COPD may be due to the existence of previously unrecognized phenotypes with different responses to therapy. This review offers the clinician caring for patients with COPD and PH a phenotype-focused approach to diagnosis and management, aimed at personalized care.

Group 3 Pulmonary Hypertension: From Bench to Bedside.

Pulmonary hypertension (PH) because of chronic lung disease is categorized as Group 3 PH in the most recent classification system. Prevalence of these diseases is increasing over time, creating a growing need for effective therapeutic options. Recent approval of the first pulmonary arterial hypertension therapy for the treatment of Group 3 PH related to interstitial lung disease represents an encouraging advancement. This review focuses on molecular mechanisms contributing to pulmonary vasculopathy in chronic hypoxia, the pathology and epidemiology of Group 3 PH, the right ventricular dysfunction observed in this population and clinical trial data that inform the use of pulmonary vasodilators in Group 3 PH.

Compassionate use of Pulmonary Vasodilators in Acute Severe Hypoxic Respiratory Failure due to COVID-19.

BackgroundThere 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.MethodsProspectively 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.ResultsFifty-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).ConclusionsThe 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.

International Practice Heterogeneity in Pediatric Left Heart Disease Related Pulmonary Hypertension

<h3>Purpose</h3> Elevated pulmonary vascular resistance (PVR) in left heart disease contributes to poor outcomes after pediatric heart transplant (HT). Medical management of high PVR pre-HT is controversial and insufficiently described. <h3>Methods</h3> We sought to characterize practice internationally by surveying physicians at pediatric HT centers via ISHLT and other networks. <h3>Results</h3> We received 49 complete responses from 39 centers in 16 countries. The majority of respondents were pediatric cardiologists (90%) practicing at centers offering pediatric heart (86%) and lung (55%) transplant. In patients with left heart failure and elevated baseline PVR, most centers (88%) perform acute vasoreactivity testing (AVT) during catheterization. Only half (51%) have established a maximum PVR for transplant eligibility, with most citing 6 WU*m² or lower (80%) [range 4-8 WU], obtained after AVT (84%). The highest post-AVT PVR ever listed ranged from 4-14.4, median 6 WU*m² (Figure). Pre-HT, phosphodiesterase 5 inhibitors are most frequently used to treat high PVR (65%); however, 31% never use pulmonary vasodilators. Implantation of a left ventricular assist device (LVAD) increases likelihood of medical therapy for PVR, though timing of initiation (pre- vs post-HT) and duration of therapy varies. Case scenarios demonstrate HT listing with post-transplant pulmonary vasodilator therapy is the favored approach for restrictive cardiomyopathy and elevated PVR, whereas LVAD +/- pulmonary vasodilators is favored for patients with dilated cardiomyopathy or postop LV dysfunction and high PVR, regardless of vasoreactivity. Most continue vasodilator therapy until PVR normalizes or short term (<6 months) post-transplant. <h3>Conclusion</h3> Practice regarding medical management of elevated PVR in children awaiting HT is heterogenous, with variable use of pulmonary vasodilators and a wide range of acceptable PVR cutoffs. Evidence-based guidelines are needed to ensure standardized care and equitable organ allocation.

Meeting abstracts from the 15th international conference on neonatal and childhood pulmonary vascular disease

Meeting abstracts from the 15th international conference on neonatal and childhood pulmonary vascular disease

Predictors Of Right Heart Failure Post Liver Transplant

Background Cardiac complications in liver cirrhosis are associated with increased mortality following liver transplant. Pre-transplant guidelines recommend risk stratification with 2D and dobutamine stress echocardiography, which may lead to coronary angiography or right heart catheterization. There is a paucity of data on the utility of RV hemodynamics during the perioperative period. Our objective was to determine if certain preoperative RV measurements distinguish which patients will experience post liver transplant RV failure. METHODS A retrospective study of liver transplant patients from 2015 through 2020 at the University of Cincinnati Medical Center was performed following IRB approval. Out of 389 patients, 13 had right heart failure based on ICD 10 code and discharge documentation. Preoperative echocardiographic data at baseline and peak stress were collected along with pre and postoperative RHC hemodynamics for comparison to age matched controls. Data was analyzed using two sample T tests in SPSS software. RESULTS Pre-operative RA pressure was higher in the RV failure group (12.5 vs. 6 p<0.001) and baseline PAPI was lower (1.97. vs. 3.54 p=0.02). Baseline TAPSE (2.05 vs. 2.52 p=0.03), stress TAPSE (2.75 vs. 3.22 p=0.02), and TAPSE augmentation (0.13 vs. 0.39 p=0.02) were lower in the RV failure group. Postoperatively, the RV failure group had higher RA pressure (10.01 vs. 7.46 p=0.04) and lower PAPI (1.44 vs. 3.34 p=0.004). There were no differences in mean PA and wedge pressure. The RV failure group had significantly more ventilator days (7.62 vs. 1.92 p<0.001), inotrope use (3.38 vs. 0 p<0.001), and pulmonary vasodilator use (1.93 vs. 0 p<0.001). Thirty day post-transplant mortality was 23% in the RV failure group and 0% in the control group. Data is represented in figure 1. DISCUSSION Cirrhosis causes hyperdynamic cardiac output leading to difficulty determining a pathologic level of dysfunction in these patients. Mean normal TAPSE and PAPI in the literature are 2.0cm and 2.75, respectively, but in our control group mean TAPSE was 2.52cm and PAPI was 3.54. This is likely explained by the high cardiac output state in cirrhosis. In the RV failure group, TAPSE and PAPI were within the normal range suggesting the need to identify a different baseline for patients with a hyperdynamic state due to cirrhosis. Mean PA pressure, commonly used to determine perioperative risk, did not have any discriminating ability between groups. Impaired RV reserve demonstrated by reduced TAPSE augmentation to stress may be a better predictor of RV failure in this patient population and identify patients that may be at risk for significant 30 day post-transplant mortality.

Use of vasopressin in persistent pulmonary hypertension of the newborn: A case series

Treatment of neonates with persistent pulmonary hypertension of newborn includes optimization of ventilatory support, use of pulmonary vasodilators, and/or inotropic support. If refractory to this management, some may require extracorporeal membrane oxygenation. We describe a case series of 10 neonates with refractory persistent pulmonary hypertension of newborn treated with vasopressin in a single tertiary center. Mean initiation time of vasopressin was at 30 h of life with a dose ranging from 10 to 85 milliunits/kg/h. Oxygenation index decreased after 12 h of vasopressin exposure (25 to 11) and mean arterial pressure improved after 1 h (45 to 58 mm Hg). Extracorporeal membrane oxygenation was averted in 50% of the cases with transient hyponatremia as the only notable side effect. Although our findings are exploratory and further research is needed to establish safety and efficacy, our experience suggests that vasopressin may have rescue properties in the management of refractory persistent pulmonary hypertension of newborn.

380 Left heart disease phenotype and use of pulmonary vasodilators in elderly patients with pulmonary arterial hypertension: the Patriarca registry

Abstract Aims The prevalence of occult left heart disease (LHD) and the feasibility of vasodilator therapy in the progressively growing population of elderly subjects with pulmonary arterial hypertension (PAH) are under scrutiny. We evaluated the presence of a LHD phenotype and the patterns of vasodilator treatment in such patients. Methods and results The PATRIARCA registry collected cross-sectional data from 180 subjects with PAH or chronic thromboembolic pulmonary hypertension and ≥70 years of age in 11 Italian centres between 1 December 2019 and 15 September 2020. After excluding patients with CTEPH or incomplete follow-up haemodynamic parameters, 77 individuals with PAH diagnosed at ≥ 65 years of age according to current guidelines were included in the analysis. A LHD phenotype was defined as follows, expanding the criteria adopted in the AMBITION trial: (i) ≥3 among body mass index ≥30 kg/m2, systemic hypertension, diabetes, and significant coronary artery disease; (ii) 2 of the risk factors for LHD above and ≥1 among permanent atrial fibrillation, left ventricular (LV) hypertrophy, LV ejection fraction &amp;lt;50%, at least moderate mitral or aortic valve disease, and left atrial dilation; (iii) pulmonary vascular resistance (PVR) between 3 and 3.75 WU or PVR between 3.75 and 6.25 WU in the presence of a pulmonary artery wedge pressure (PAWP) of 13–15 mmHg. Forty-one (53%) patients had a LHD phenotype according to the most recent clinical and haemodynamic evaluation, which was performed 16 (4–35) months after diagnosis (Figure). As per definition, they had higher rates of comorbidities and more often echocardiographic signs of LHD (not shown). The frequency of NYHA classes I–II was comparable between the two groups, while the 6 min-walking distance tended to be lower in subjects with a LHD phenotype than in those without (Figure, left panel). Furthermore, these latter had lower PVR and higher PAWP. No differences were seen in treatment with pulmonary vasodilators, with around 50% of patients receiving double oral combination therapy in both groups (Figure, right panel). During the study period, 7 (17%) and 4 (11%) patients died in the LHD and no-LHD groups, respectively (P = 0.40). Conclusions In this real-world cohort of elderly patients, a LHD phenotype was common despite an initial haemodynamic diagnosis of PAH. However, it did not appear to cause simplification or discontinuation of pulmonary vasodilator therapy. Longitudinal studies are needed to determine whether and how a LHD phenotype affects the use and effects of PAH drugs in the elderly.

Inhaled Pulmonary Vasodilator Utilization and Cost Following Initiation of a Protocol in a Quaternary Academic Heart Center Intensive Care Unit

To examine the use of inhaled nitric oxide (iNO) and inhaled epoprostenol (iPGI2) before and after implementation of an iPGI2-preferential protocol and the associated cost differences after rollout. A single-center, retrospective analysis. A quaternary university hospital. All patients admitted to the Heart Center Intensive Care Unit (HCICU) who required inhaled pulmonary vasodilator use between December 2017 and November 2019. None. The HCICU comprised 84% of hospital-wide iNO utilization and 59% of hospital-wide iPGI2 use across the entire study period. There was no significant difference in postsurgical HCICU admission rates across the study period. There was a significant decrease in iNO mean monthly use from 578 ± 230 to 69 ± 71 hours, and a significant concurrent increase in iPGI2 from 756 ± 443 to 1,210 ± 547 hours after the implementation of a protocol. There were no changes in the average length of ICU stay between the 2 time periods. The protocol implementation led to a projected annual savings of roughly $1,180,000. These findings showed that multidisciplinary protocol development and implementation can have a substantial impact on medication utilization and lead to significant reductions in cost.

Management of PH-ILD: Past, Present, and Future

Pulmonary hypertension associated with interstitial lung disease signifies worse outcomes. Given previous negative clinical trials, the use of pulmonary vasodilators in pulmonary hypertension associated with interstitial lung disease has traditionally been on a case-by-case basis; however, the recent INCREASE study has led to the first and milestone approval of inhaled treprostinil for this population. This review discusses the management of pulmonary hypertension associated with interstitial lung disease from the pulmonary vascular perspective, with an emphasis on clinical trials in this population.

Pulmonary vascular disease in Fontan circulation-is there a rationale for pulmonary vasodilator therapies?

The Fontan circulation is a palliative concept for patients with univentricular hearts. The central veins are connected directly to the pulmonary arteries (cavo-pulmonary connection) to separate the pulmonary and the systemic circulation. There is no sub-pulmonary ventricle that generates pressure to drive blood through the pulmonary arteries. Pulmonary blood flow is determined by central venous pressure (CVP) and pulmonary vascular resistance (PVR). The capability of the Fontan circulation to compensate for alterations in PVR is limited, as CVP can only be increased within narrow ranges without adverse clinical consequences. Consequently, systemic ventricular preload and cardiac output are dependent on a healthy lung with low PVR. Failure of the Fontan circulation is relatively common. In addition to ventricular dysfunction, maladaptive pulmonary vascular remodeling resulting in increased pulmonary resistance may play a key role. The pathophysiology of the maladaptive vascular processes remains largely unclear and diagnosis of an increased PVR is challenging in Fontan circulation as accurate measurement of pulmonary arterial blood flow is difficult. In the absence of a sub-pulmonary ventricle, pulmonary artery pressure will almost never reach the threshold conventionally used to define pulmonary arterial hypertension. There is a need for markers of pulmonary vascular disease complementary to invasive hemodynamic data in Fontan patients. In order to treat or prevent failure of the Fontan circulation, pathophysiological considerations support the use of pulmonary vasodilators to augment pulmonary blood flow and systemic ventricular preload and lower CVP. However, to date the available trial data have neither yielded enough evidence to support routine use of pulmonary vasodilators in every Fontan patient nor have they been helpful in defining subgroups of patients that might benefit from such therapies. This review discusses potential pathomechanisms of pulmonary vascular disease; it summarizes the current knowledge of the effects and efficacy of pulmonary vasodilator therapy in Fontan patients and tries to outline areas of potential future research on the diagnosis and treatment of pulmonary vascular disease and Fontan failure.