Significance of colonization by antibiotic-resistant organisms prior to congenital heart disease surgery in children from low- to middle-income countries sent by non-governmental organizations to Switzerland.

PURPOSE: Children with congenital heart disease (CHD) from low- to middle-income countries (LMIC) are suspected to have a high prevalence of antibiotic-resistant microorganisms (ARMOs) carriage, but data are currently lacking. Carriage of ARMOs could impact the post-operative course in pediatric intensive care unit (PICU). The aim of the study was to assess the prevalence of ARMOs carriage in children with CHD from LMIC and its impact on post-operative outcomes. METHODS: This was a retrospective monocentric study from 01/2019 to 12/2022. Included patients were children (0-18 years) from a LMIC admitted after CHD surgery and with AMRO screening performed the week before. Infections and post-operative evolution were compared based on ARMOs carriage status. FINDINGS: Among 224 surgeries (median age 38.5 months (IQR 22-85.5)), ARMOs carriage was evidenced in 95 cases (42.4%). Main organisms isolated were Extended Spectrum Beta-Lactamase (ESBL) producing E. coli (75/224) 33.5%)) and ESBL-K. pneumoniae (30/224) 13.4%)). Median mechanical ventilation duration was 1 day (IQR 0-1), PICU stay 3 days (IQR 2-4) and hospital stay 6.5 days (IQR 5-10). A total of 17 infectious episodes occurred in 15 patients, mostly consisting in hospital-acquired pneumonia (HAP) (12/17). Only two infections were caused by a colonizing ARMO. Occurrence of infections and patients' outcome were similar between ARMO carriers and non-carriers. Higher use of carbapenems (6 (6.3%) vs 1 (0.8%), p = 0.04) and a trend to a higher use of vancomycin (14 (13.7%) vs 9 (6.9%), p = 0.04) in case of ARMOs carriage. Applying current guidelines, negative swab screening could have led to sparing most of empirical vancomycin therapy (11/12) for HAP based on current guidelines. CONCLUSION: Prevalence of AMROs carriage is high in children from LMIC and has a limited impact on patients' outcome. However, ARMOs carriage leads to higher consumption of antibiotics. Screening may help saving use of broad-spectrum antibiotic in non-carrier patients.

Long-term safety and tolerability of ambrisentan treatment for pediatric patients with pulmonary arterial hypertension: An open-label extension study.

This open-label, extension study assessed long-term safety, tolerability, and efficacy of ambrisentan in a pediatric population (age 8- < 18 years) with pulmonary arterial hypertension (PAH). Following completion of a 6-month, randomized study, participants entered the long-term extension at individualized ambrisentan dosages (2.5/5/7.5 or 10 mg/day). Safety assessments included adverse events (AEs), AEs of special interest, and serious AEs (SAEs); efficacy outcomes included 6-min walking distance (6MWD) and World Health Organization functional class (WHO FC). Thirty-eight of 41 (93%) randomized study participants entered the extension; 21 (55%) completed (reaching age 18 years). Most participants received concomitant phosphodiesterase-5 inhibitors (n = 25/38, 66%). Median ambrisentan exposure was 3.5 years. Most participants experienced ≥ 1 AE (n = 34/38, 89%), and 21 (55%) experienced SAEs, most commonly worsening PAH (n = 3/38, 8%), acute cardiac failure, pneumonia, or anemia (n = 2/38; 5% each); none considered ambrisentan-related. Seven participants (18%) died, with recorded reasons (MedDRA preferred term): cardiac failure (n = 2), PAH (n = 2), COVID-19 (n = 1), acute right ventricular failure (n = 1), and failure to thrive (n = 1); median time to death: 5.2 years. Anemia and hepatotoxicity AEs were generally mild to moderate and did not require ambrisentan dose adjustment. Assessed at study end in 29 participants (76%), mean 6MWD improved by 17% (standard deviation: 34.3%), and all (29/29, 100%) had improved or unchanged WHO FC.    Conclusion: Long-term weight-based ambrisentan dosing, alone or combined with other PAH therapies in children with PAH aged 8- < 18 years, exhibited tolerability and clinical improvements consistent with prior randomized study results.    Trial registration: NCT01342952, April 27, 2011. What is Known: • The endothelin receptor antagonist, ambrisentan, is indicated for treatment of pulmonary arterial hypertension (PAH). Previous studies have shown similar efficacy and tolerability in pediatric patients as in adults. What is New: • This open-label extension study assessed the long-term use of ambrisentan in pediatric patients (8-<18 years) with PAH, most of whom were also receiving recommended background PAH treatment. • Weight-based dosing of ambrisentan, given alone or in combination with other PAH therapies, was well tolerated with clinical improvements consistent with prior randomized study results.

[Risks of magistral preparations in pediatrics]. / Risques des préparations magistrales en pédiatrie.

Vasoreactive pulmonary arterial hypertension (PAH) in children is a form of idiopathic PAH that responds to vasoreactive testing with nitric oxide (NO) by a significant decrease of pulmonary vascular resistances and pressure. Oral calcium channel antagonists (CCA) that allow pulmonary arterial vasodilation are the treatment of choice. The therapeutic effect is strongly depending on adequate drug intake. In growing children, drug dose must be adapted to weight. In case of unavailability of low-dose pharmaceutical preparations, officinal formulations become mandatory. Officinal formulations may be related to a multitude of errors at different steps including prescription, transcription, preparation and administration. This may have life-threatening consequences for the child.To illustrate this, we report a case of a compounding error with underdosage of CCA, leading to acute cardiovascular failure in an adolescent with vasoreactive PAH.

L'hypertension artérielle pulmonaire (HTAP) vasoréactive chez l'enfant est une forme d'HTAP idiopathique qui répond au test de vasoréactivité au monoxyde d'azote (NO) par une diminution significative des pressions et résistances vasculaires pulmonaires. Le traitement de choix de cette forme d'HTAP est l'administration d'antagonistes des canaux calciques (ACC) par voie orale. Ce traitement entraîne une vasodilatation artérielle pulmonaire, elle-même étroitement dépendante de la prise adéquate du médicament. Chez les enfants en croissance, la dose du médicament doit être adaptée au poids. De façon générale, en l'absence de préparation à faible dose disponible dans les laboratoires pharmaceutiques, l'utilisation de formulations officinales devient obligatoire. De la prescription à l'administration, en passant par la transcription et la préparation, de nombreuses erreurs humaines et techniques peuvent survenir qui peuvent impacter la morbi-mortalité de l'enfant. Nous rapportons le cas d'une adolescente avec HTAP vasoréactive chez qui une erreur de préparation magistrale avec sous-dosage de l'ACC a conduit à une décompensation cardio-vasculaire aiguë et discutons de mesures préventives potentielles.

Application of a modified clinical classification for pulmonary arterial hypertension associated with congenital heart disease in children: emphasis on atrial septal defects and transposition of the great arteries. An analysis from the TOPP registry.

Aims: A proportion of patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) do not fit in the current classification. We aimed to analyse the applicability of an adapted clinical classification of PAH-CHD to pediatric patients using the TOPP-1 registry (Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension) and focus on atrial septal defects (ASD) and transposition of the great arteries (TGA). Methods and results: Hemodynamic and clinical data of all patients with PAH-CHD in the TOPP cohort were reviewed. Patients were classified according to predefined ABCDE categories (A: Eisenmenger syndrome, B: left-to-right shunt, C: coincidental defects, including all ASDs, D: corrected CHD, E: TGA), or as complex CHD (group 5), by 2 independent investigators. In case of disagreement, a third reviewer could either settle a final decision, or the patient was deemed not classifiable. Survival curves were calculated for each group and compared to idiopathic PAH patients of the registry. A total of 223 out of 531 patients in the registry had PAH-CHD, and 193 were categorized to the following groups: A 39(20%), B 27(14%), C 62(32%) including 43 ASDs, D 58(30%), E 7(4%), whereas 6 patients were categorized as group 5, and 10 patients were unable to be classified. No survival difference could be demonstrated between the groups. Conclusions: This modified classification seems to be more applicable to pediatric PAH-CHD patients than the previous classification, but some patients with PAH-CHD who never had a shunt remain unclassifiable. The role of ASD in pediatric PH should be reconsidered.

Infective Endocarditis Due to Kingella kingae.

Infective endocarditis due to Kingella kingae is a rare but serious invasive infection that occurs mostly in children. Recent advances in nucleic acid amplification testing as well as in cardiac imaging have enabled more accurate diagnosis. A good understanding of the epidemiology and virulence factors remains crucial to guide the therapeutic approach. Here, we synthesize the current state of knowledge on epidemiological features, pathophysiological insights, complications, and therapy regarding Kingella kingae endocarditis in children and adults. Finally, throughout this comprehensive review, knowledge gaps and areas for future research are also identified.

Long-term outcome of children with newly diagnosed pulmonary arterial hypertension: results from the global TOPP registry.

BACKGROUND AND AIMS: The Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension (TOPP) registry is a global network established to gain insights into the disease course and long-term outcomes of paediatric pulmonary arterial hypertension (PAH). Previously published cohorts in paediatric PAH are obscured by survival bias due to the inclusion of both prevalent (previously diagnosed) and incident (newly diagnosed) patients. The current study aims to describe long-term outcome and its predictors in paediatric PAH, exclusively of newly diagnosed patients. METHODS AND RESULTS: Five hundred thirty-one children with confirmed pulmonary hypertension, aged ≥3 months and <18 years, were enrolled in the real-world TOPP registry at 33 centres in 20 countries, from 2008 to 2015. Of these, 242 children with newly diagnosed PAH with at least one follow-up visit were included in the current outcome analyses. During long-term follow-up, 42 (17.4%) children died, 9 (3.7%) underwent lung transplantation, 3 (1.2%) atrial septostomy, and 9 (3.7%) Potts shunt palliation (event rates: 6.2, 1.3, 0.4, and 1.4 events per 100 person-years, respectively). One-, three-, and five-year survival free from adverse outcome was 83.9%, 75.2%, and 71.8%, respectively.Overall, children with open (unrepaired or residual) cardiac shunts had the best survival rates. Younger age, worse World Health Organization functional class, and higher pulmonary vascular resistance index were identified as independent predictors of long-term adverse outcome. Younger age, higher mean right atrial pressure, and lower systemic venous oxygen saturation were specifically identified as independent predictors of early adverse outcome (within 12 months after enrolment). CONCLUSION: This comprehensive analysis of survival from time of diagnosis in a large exclusive cohort of children newly diagnosed with PAH describes current-era outcome and its predictors.

Dual-energy computed tomography to detect early pulmonary vascular changes in children with sickle cell disease: a pilot study.

Introduction: Pulmonary hypertension (PH) is a rare but fatal complication of sickle cell disease (SCD) that is possibly reversible if treated early. Dual-energy computed tomography (DECT) is a valuable tool for diagnosing PH. We attempted to determine if DECT can detect early signs of PH in children with SCD. Methods: This prospective observational pilot study was conducted at the Geneva University Hospitals and was approved by the local human ethics committee (CCER 2019-01975). A written informed consent was obtained from the patients and/or their legal guardian. Eight children (consisting of five girls and three boys) with homozygous SCD were included in the study. They underwent full cardiological workup using transthoracic echocardiography (TTE) and cardiopulmonary exercise test (CPET), as well as DECT. Results: The median age of the children was 11 years old (range 8-12). All patients exhibited a normal biventricular systo-diastolic function using the TTE. The median tricuspid regurgitant jet velocity value was 2.24 m/s (range 1.96-2.98). Four children were found to have signs of vasculopathy detected on DECT. Of them, two had abnormal screening test results. They both had an increased VE/VCO2 slope during CPET and an increased TVR of >2.5 m/s on TTE. Conclusion: DECT is capable of identifying early signs of pulmonary vascular disease in children with SCD. Further studies are needed to understand the correlation between DECT abnormalities and hemodynamic pulmonary circulation better.

Triple switch' aortic and pulmonary root inversion and modified Senning procedure for anatomically complex left transposition of the great arteries with inlet ventricular septal defect and pulmonary stenosis.

Left transposition of the great arteries with inlet ventricular septal defect and pulmonary stenosis is a relatively uncommon cardiac malformation. Two surgical treatments are available: double switch or physiological correction. The choice of surgical technique depends on the results of a discussion between the family and the surgeon. Choosing the appropriate technique is challenging because all options present various complications and benefits. We present a 'triple switch' aortic and pulmonary root inversion and modified Senning procedure for an anatomically complex left transposition of the great arteries with an inlet ventricular septal defect and pulmonary stenosis.

Decompressive hemicraniectomy in pediatric malignant arterial ischemic stroke: a case-based review.

PURPOSE: Malignant stroke is a life-threatening emergency, with a high mortality rate (1-3). Despite strong evidence showing decreased morbidity and mortality in the adult population, decompressive hemicraniectomy (DCH) has been scarcely reported in the pediatric stroke population, and its indication remains controversial, while it could be a potential lifesaving option. METHODS AND RESULTS: We performed an extensive literature review on pediatric malignant arterial ischemic stroke (pmAIS) and selected 26 articles reporting 97 cases. Gathering the data together, a 67% mortality rate is observed without decompressive therapy, contrasting with a 95.4% survival rate with it. The median modified Rankin score (mRS) is 2.1 after surgery with a mean follow-up of 31.8 months. For the 33% of children who survived without surgery, the mRS is 3 at a mean follow-up of 19 months. As an illustrative case, we report on a 2-year-old girl who presented a cardioembolic right middle cerebral artery stroke with subsequent malignant edema and ongoing cerebral transtentorial herniation in the course of a severe myocarditis requiring ECMO support. A DCH was done 32 h after symptom onset. At the age of 5 years, she exhibits an mRS of 3. CONCLUSION: Pediatric stroke with malignant edema is a severe condition with high mortality rate if left untreated and often long-lasting consequences. DCH might minimize the vicious circle of cerebral swelling, increasing intracranial pressure and brain ischemia. Our literature review underscores DCH as an efficient therapeutic measure management of pmAIS even when performed after a significant delay; however, long-lasting morbidities remain high.

Successful heart transplant in a child with congenital core myopathy and delayed-onset restrictive cardiomyopathy due to recessive mutations in the titin (TTN) gene.

BACKGROUND: Mutations in the TTN gene, encoding the muscle filament titin, are a major cause of inherited dilated cardiomyopathy. Early-onset skeletal muscle disorders due to recessive TTN mutations have recently been described, sometimes associated with cardiomyopathies. CASE DESCRIPTION: We report the case of a boy with congenital core myopathy due to compound heterozygosity for TTN variants. He presented in infancy with rapidly evolving restrictive cardiomyopathy, requiring heart transplantation at the age of 5 years with favorable long-term cardiac and neuromuscular outcome. CONCLUSION: Heart transplantation may have a role in selected patients with TTN-related congenital myopathy with disproportionally severe cardiac presentation compared to skeletal and respiratory muscle involvement.

Pulmonary vascular disease as a complication of pediatric congenital heart diseases.

Congenital and acquired heart diseases can cause pulmonary hypertension (PH) in children, either by increasing pulmonary blood flow (PBF), left atrial pressure (LAp), and/or pulmonary vascular resistance (PVR). Pathophysiological process of pulmonary vascular disease (PVD) in different types of congenital heart diseases (CHDs) are reviewed hereafter. As with other types of PH, a rigorous diagnostic evaluation is mandatory to characterize the etiology of the PH, rule out other or additional causes of PH, and establish a risk profile. Cardiac catheterization remains the gold standard exam for PH diagnosis. Treatment of pulmonary arterial hypertension (PAH) associated with CHD (PAH-CHD) can then be started according to the recent guidelines recommendations, although most of the evidence is extrapolated from studies on other causes of PAH. PH in pediatric heart disease is often multifactorial, and sometimes unclassifiable, making the management of these patients complicated. The operability of patients with a prevalent left-to-right shunt and increase of PVR, the management of children with PH associated with left-sided heart disease, the challenges of pulmonary vascular disorders in children with univentricular heart physiology and the role of vasodilator therapy in failing Fontan patients are some of the hot topics discussed in this review.

An Implantable Wireless System for Remote Hemodynamic Monitoring of Heart Failure Patients.

This article presents an implantable wireless system for remote hemodynamic monitoring, which enables direct, continuous (24/7), and simultaneous measurement of pulmonary arterial pressure (PAP) and cross-sectional area (CSA) of the artery. The implantable device, which measures 3.2 mm × 2 mm × 10 mm, comprises a piezoresistive pressure sensor, an ASIC implemented in 180-nm CMOS, a piezoelectric ultrasound (US) transducer, and a nitinol anchoring loop. An energy-efficient pressure monitoring system, which employs duty-cycling and spinning excitation technique, achieves 0.44 mmHg resolution in a pressure range from -135 mmHg to +135 mmHg and consumes 1.1 nJ conversion energy. The artery diameter monitoring system utilizes the inductive characteristic of the implant's anchoring loop and achieves 0.24 mm resolution within a diameter range of 20 mm to 30 mm, four times higher than echocardiography lateral resolution. The wireless US power and data platform enables simultaneous power and data transfer employing a single piezoelectric transducer in the implant. The system is characterized with an 8.5 cm tissue phantom and achieves a US link efficiency of 1.8%. The uplink data is transmitted by using an ASK modulation scheme parallel to the power transfer and achieves a modulation index of 26%. The implantable system is tested in an in-vitro experimental setup, which emulates the arterial blood flow, and accurately detects fast pressure peaks for systolic and diastolic pressure changes at both 1.28 MHz and 1.6 MHz US powering frequencies, with corresponding uplink data rates of 40 kbps and 50 kbps.

Use of CO2-Derived Variables in Cardiac Intensive Care Unit: Pathophysiology and Clinical Implications.

Shock is a life-threatening condition, and its timely recognition is essential for adequate management. Pediatric patients with congenital heart disease admitted to a cardiac intensive care unit (CICU) after surgical corrections are particularly at risk of low cardiac output syndrome (LCOS) and shock. Blood lactate levels and venous oxygen saturation (ScVO2) are usually used as shock biomarkers to monitor the efficacy of resuscitation efforts, but they are plagued by some limitations. Carbon dioxide (CO2)-derived parameters, namely veno-arterial CO2 difference (ΔCCO2) and the VCO2/VO2 ratio, may represent a potentially valuable addition as sensitive biomarkers to assess tissue perfusion and cellular oxygenation and may represent a valuable addition in shock monitoring. These variables have been mostly studied in the adult population, with a strong association between ΔCCO2 or VCO2/VO2 ratio and mortality. In children, particularly in CICU, few studies looked at these parameters, while they reported promising results on the use of CO2-derived indices for patients' management after cardiac surgeries. This review focuses on the physiological and pathophysiological determinants of ΔCCO2 and VCO2/VO2 ratio while summarizing the actual state of knowledge on the use of CO2-derived indices as hemodynamical markers in CICU.

Growing up with Idiopathic Pulmonary Arterial Hypertension: An Arduous Journey.

Idiopathic pulmonary arterial hypertension (IPAH) is an uncommon and severe disease. We report the case of a 7-year-old boy investigated for cardiac murmur and exercise intolerance. Pulmonary hypertension (PH) was suspected at clinical examination and confirmed by echocardiography and cardiac catheterization. This case of pulmonary hypertension was classified as idiopathic given the negative etiological investigation. Vasoreactive testing with oxygen and nitric oxide was negative. Therefore, treatment with sildenafil (1.4 mg/kg/d) and bosentan (3 mg/kg/d) was initiated. This allowed the stabilization of, but not a decrease in, pulmonary artery pressure for the next 5 years, during which the patient's quality of life was significantly reduced. At a later follow-up, the estimated pulmonary pressure was found to have increased and become supra-systemic, with a consequent deterioration in the child's condition. This led to the decision to enter him into a clinical trial that is still ongoing. Idiopathic pulmonary arterial hypertension is a severe disease that can present with non-specific symptoms, such as asthenia and exercise limitation, which are important not to trivialize. The disease is associated with significantly decreased quality of life in affected children and carries a high burden in terms of mortality and morbidity. The current knowledge about IPAH in children is reviewed, with a particular focus on the future prospects for its treatment and the related quality of life of patients.

Three-dimensional printing and virtual reconstruction in surgical planning of double-outlet right ventricle repair.

Objectives: For more than a decade, 3-dimensional (3D) printing has been identified as an innovative tool for the surgical planning of double-outlet right ventricle (DORV). Nevertheless, lack of evidence concerning its benefits encourages us to identify valuable criteria for future prospective trials. Methods: We conducted a retrospective study involving 10 patients with DORV operated between 2015 and 2019 in our center. During a preoperative multidisciplinary heart team meeting, we harvested surgical decisions following a 3-increment step process: (1) multimodal imaging; (2) 3D virtual valvular reconstruction (3DVVR); and (3) 3D-printed heart model (3DPHM). The primary outcome was the proportion of predicted surgical strategy following each of the 3 steps, compared with the institutional retrospective surgical strategy. The secondary outcome was the change of surgical strategy through 3D modalities compared with multimodal imaging. The incremental benefit of the 3DVVR and 3DPHM over multimodal imaging was then assessed. Results: The operative strategy was predicted in 5 cases after multimodal imaging, in 9 cases after 3DVVR, and the 10 cases after 3DPHM. Compared with multimodal imaging, 3DVVR modified the strategy for 4 cases. One case was correctly predicted only after 3DPHM inspection. Conclusions: 3DVVR and 3DPHM improved multimodal imaging in the surgical planning of patients with DORV. 3DVVR allowed a better appreciation of the relationships between great vessels, valves, and ventricular septal defects. 3DPHM offers a realistic preoperative view at patient scale and enhances the evaluation of outflow tract obstruction. Our retrospective study demonstrates benefits of preoperative 3D modalities and supports future prospective trials to assess their impact on postoperative outcomes.

Home Respiratory Polygraphy and Spirometry in Normal Weight and Children with Obesity Suspected for Obstructive Sleep Apnea Syndrome: Are There Any Associations?

Aim: It is known that children and adolescents with obesity are more prone to obstructive sleep apnea syndrome (OSAS) and that their lung function may show some disturbance. Literature is scarce about potential associations; therefore, we aimed to study the relationship between OSAS, lung function, and adiposity in a population of children suspected of OSAS. Material and Methods. We performed home respiratory polygraphy and spirometry in all subjects. The relationships between body mass index z-score (zBMI), polygraphy, and spirometry data were analyzed. Results: We recruited 81 subjects aged between 5 and 16 years, 63% being obese. 43.2% of subjects were diagnosed with OSAS (32.1% mild, 4.9% moderate, and 6.2% severe). We found no correlation between respiratory polygraphy and the zBMI. The mean spirometric value FEV1, FVC, and FEV1/FVC ratio z's were normal in all subjects, whereas FVC z's and FEV1/FVC ratio z's were significantly positively related for obesity and negatively for normal weight (p < 0.05). FEV1 z's was inversely correlated to the percentage of analyzed time passed below 90% of SpO2 (r = -0.224, p = 0.044). All subjects with FEV1 (n = 8) and/or FVC (n = 9) z's below the lower limit for normal (LLN) had an AHI ≥ 1 (FEV1: p = 0.001; FVC: p < 0.001), especially subjects with normal weight (FEV1: p = 0.003; FVC: p = 0.010). Conclusion: When comparing normal-weight children and adolescents with obesity, the prevalence of OSAS but not spirometric values was strongly related to BMI z-score, probably because obesity engenders advanced puberty and an accelerated growth spurt. FEV1 was more frequently

The Influence of Methods for Cardiac Output Determination on the Diagnosis of Precapillary Pulmonary Hypertension: A Mathematical Model.

Background: precapillary pulmonary hypertension (PH, PcPH) is now defined as a mean pulmonary artery pressure (mPAP) > 20 mmHg, a pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg and a pulmonary vascular resistance (PVR) > 2 WU. For PVR calculation, the measurement of cardiac output (CO) is necessary. It is generally measured using thermodilution. However, recent data showed that the agreement with direct Fick method, historically the gold standard, is less than previously reported. We aimed to create a mathematical model that calculated the probability of being classified differently (PcPH or unclassified PH) if CO measured by direct Fick was used instead of thermodilution for any individual patients with a mPAP > 20 mmHg and a PAWP ≤ 15 mmHg. Methods: The model is based on Bland and Altman analysis with a normally distributed difference of cardiac output, fixed 1.96 standard deviation of bias, bias and physiological cardiac output limits. Results: Following a literature review of the studies comparing CO measured with direct Fick and thermodilution, we fixed the 1.96 standard deviation of bias at 2 L/min, bias at 0 L/min and physiological resting CO limits between 1.3 L/min and 10.2 L/min. Conclusions: This model can help the clinician to evaluate the potential benefit of measuring CO using direct Fick during the diagnostic work-up and its utility in confirming or ruling out a diagnosis of PcPH in any given patient with a mPAP > 20 mmHg and a PAWP ≤ 15 mmHg.