Characteristics and risk profiles of patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension living permanently at >2500 m of high altitude in Ecuador.

Over 80 Mio people worldwide live >2500 m, including at least as many patients with pulmonary vascular disease (PVD), defined as pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH), as elsewhere (estimated 0.1‰). Whether PVD patients living at high altitude have altered disease characteristics due to hypobaric hypoxia is unknown. In a cross-sectional study conducted at the Hospital Carlos Andrade Marin in Quito, Ecuador, located at 2840 m, we included 36 outpatients with PAH or CTEPH visiting the clinic from January 2022 to July 2023. We collected data on diagnostic right heart catheterization, treatment, and risk factors, including NYHA functional class (FC), 6-min walk distance (6MWD), and NT-brain natriuretic peptide (BNP) at baseline and at last follow-up. Thirty-six PVD patients (83% women, 32 PAH, 4 CTEPH, mean ± SD age 44 ± 13 years, living altitude 2831 ± 58 m) were included and had the following baseline values: PaO2 8.2 ± 1.6 kPa, PaCO2 3.9 ± 0.5 kPa, SaO2 91 ± 3%, mean pulmonary artery pressure 53 ± 16 mmHg, pulmonary vascular resistance 16 ± 4 WU, 50% FC II, 50% FC III, 6MWD 472 ± 118 m, BNP 490 ± 823 ng/L. Patients were treated for 1628 ± 1186 days with sildenafil (100%), bosentan (33%), calcium channel blockers (33%), diuretics (69%), and oxygen (nocturnal 53%, daytime 11%). Values at last visit were: FC (II 75%, III 25%), 6MWD of 496 ± 108 m, BNP of 576 ± 5774 ng/L. Compared to European PVD registries, ambulatory PVD patients living >2500 m revealed similar blood gases and relatively low and stable risk factor profiles despite severe hemodynamic compromise, suggesting that favorable outcomes are achievable for altitude residents with PVD. Future studies should focus on long-term outcomes in PVD patients dwelling >2500 m.

Exercise-Induced Pulmonary Hypertension in Long-Term Survivors of Congenital Diaphragmatic Hernia.

OBJECTIVE: To determine the prevalence of exercise-induced pulmonary hypertension (PH) among long-survivors of congenital diaphragmatic hernia repair. STUDY DESIGN: This is a single-center, retrospective cohort study of CDH survivors who underwent exercise stress echocardiography (ESE) at Boston Children's Hospital from January 2006 to June 2020. PH severity was assessed by echocardiogram at baseline and after exercise. Patients were categorized by right ventricular systolic pressure (RVSP) after exercise: Group 1 - no or mild PH; and Group 2 - moderate or severe PH (RVSP ≥ 60 mmHg or ≥ ½ systemic blood pressure). RESULTS: Eighty-four patients with CDH underwent 173 ESE with median age 8.1 (4.8 - 19.1) years at first ESE. Sixty-four patients were classified as Group 1, 11 as Group 2, and 9 had indeterminate RVSP with ESE. Moderate to severe PH after exercise was found in 8 (10%) patients with no or mild PH at rest. Exercise-induced PH was associated with larger CDH defect size, patch repair, use of ECMO, supplemental oxygen at discharge, and higher WHO functional class. Higher VE/VCO2 slope, lower peak oxygen saturation, and lower percent predicted FEV1, and FEV1/FVC ratio were associated with Group 2 classification. ESE changed management in 9/11 Group 2 patients. PH was confirmed in all 5 Group 2 patients undergoing cardiac catheterization after ESE. CONCLUSIONS: Among long-term CDH survivors, 10% had moderate-severe exercise-induced PH on ESE, indicating ongoing pulmonary vascular abnormalities. Further studies are needed to optimally define PH screening and treatment for patients with repaired CDH.

Pulmonary Hypertension in Infants and Children with Vein of Galen Malformation and Association with Clinical Outcomes.

OBJECTIVE: To assess the extent and resolution of pulmonary hypertension (PH), cardiovascular factors, and echocardiographic findings associated with mortality in infants and children with vein of Galen malformation (VOGM). STUDY DESIGN: We performed a retrospective review of 49 consecutive children with VOGM admitted to Boston Children's Hospital from 2007 to 2020. Patient characteristics, echocardiographic data, and hospital course were analyzed for 2 cohorts based on age at presentation to Boston Children's Hospital: group 1 (age ≤60 days) or group 2 (age >60 days). RESULTS: Overall hospital survival was 35 of 49 (71.4%); 13 of 26 (50%) in group 1 and 22 of 23 (96%) in group 2 (P < .001). High-output PH (P = .01), cardiomegaly (P = .011), intubation (P = .019), and dopamine use (P = .01) were significantly more common in group 1 than group 2. Among patients in group 1, congestive heart failure (P = .015), intubation (P < .001), use of inhaled nitric oxide (P = .015) or prostaglandin E1 (P = .030), suprasystemic PH (P = .003), and right-sided dilation were significantly associated with mortality; in contrast, left ventricular volume and function, structural congenital heart disease, and supraventricular tachycardia were not associated. Inhaled nitric oxide achieved no clinical benefit in 9 of 11 treated patients. Resolution of PH was associated with overall survival (P < .001). CONCLUSIONS: VOGM remains associated with substantial mortality among infants presenting at ≤60 days of life owing to factors associated with high output PH. Resolution of PH is an indicator associated with survival and a surrogate end point for benchmarking outcomes.

Exertional Cardiac and Pulmonary Vascular Hemodynamics in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Exertional dyspnea is a cardinal manifestation of heart failure with reduced ejection fraction (HFrEF), but quantitative data regarding exertional hemodynamics are lacking. OBJECTIVES: We sought to characterize exertional cardiopulmonary hemodynamics in patients with HFrEF. METHODS: We studied 35 patients with HFrEF (59 ± 12 years old, 30 males) who completed invasive cardiopulmonary exercise testing. Data were collected at rest, at submaximal exercise and at peak effort on upright cycle ergometry. Cardiovascular and pulmonary vascular hemodynamics were recorded. Fick cardiac output (Qc) was determined. Hemodynamic predictors of peak oxygen uptake (VO2) were identified. RESULTS: Left ventricular ejection fraction and cardiac index were 23% ± 8% and 2.9 ± 1.1 L/min/m2, respectively. Peak VO2 was 11.8 ± 3.3 mL/kg/min, and the ventilatory efficiency slope was 53 ± 13. Right atrial pressure increased from rest to peak exercise (4 ± 5 vs 7 ± 6 mmHg,). Mean pulmonary arterial pressure increased from rest to peak exercise (27 ± 13 vs 38 ± 14 mmHg). Pulmonary artery pulsatility index increased from rest to peak exercise, while pulmonary arterial capacitance and pulmonary vascular resistance declined. CONCLUSIONS: Patients with HFrEF suffer from marked increases in filling pressures during exercise. These findings provide new insight into cardiopulmonary abnormalities contributing to impairments in exercise capacity in this population. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT03078972.

Pulmonary Hypertension in Children with Down Syndrome: Results from the Pediatric Pulmonary Hypertension Network Registry.

OBJECTIVE: To characterize distinct comorbidities, outcomes, and treatment patterns in children with Down syndrome and pulmonary hypertension in a large, multicenter pediatric pulmonary hypertension registry. STUDY DESIGN: We analyzed data from the Pediatric Pulmonary Hypertension Network (PPHNet) Registry, comparing demographic and clinical characteristics of children with Down syndrome and children without Down syndrome. We examined factors associated with pulmonary hypertension resolution and a composite outcome of pulmonary hypertension severity in the cohort with Down syndrome. RESULTS: Of 1475 pediatric patients with pulmonary hypertension, 158 (11%) had Down syndrome. The median age at diagnosis of pulmonary hypertension in patients with Down syndrome was 0.49 year (IQR, 0.21-1.77 years), similar to that in patients without Down syndrome. There was no difference in rates of cardiac catheterization and prescribed pulmonary hypertension medications in children with Down syndrome and those without Down syndrome. Comorbidities in Down syndrome included congenital heart disease (95%; repaired in 68%), sleep apnea (56%), prematurity (49%), recurrent respiratory exacerbations (35%), gastroesophageal reflux (38%), and aspiration (31%). Pulmonary hypertension resolved in 43% after 3 years, associated with a diagnosis of pulmonary hypertension at age <6 months (54% vs 29%; P = .002) and a pretricuspid shunt (65% vs 38%; P = .02). Five-year transplantation-free survival was 88% (95% CI, 80%-97%). Tracheostomy (hazard ratio [HR], 3.29; 95% CI, 1.61-6.69) and reflux medication use (HR, 2.08; 95% CI, 1.11-3.90) were independently associated with a composite outcome of severe pulmonary hypertension. CONCLUSIONS: Despite high rates of cardiac and respiratory comorbidities that influence the severity of pulmonary hypertension, children with Down syndrome-associated pulmonary hypertension generally have a survival rate similar to that of children with non-Down syndrome-associated pulmonary hypertension. Resolution of pulmonary hypertension is common but reduced in children with complicated respiratory comorbidities.

Longitudinal B-Type Natriuretic Peptide Levels Predict Outcome in Infants with Congenital Diaphragmatic Hernia.

OBJECTIVE: To evaluate B-type natriuretic peptide (BNP) as a longitudinal biomarker of clinical outcome in infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: We conducted a retrospective study of 49 infants with CDH, classifying the cohort by respiratory status at 56 days, based on a proposed definition of bronchopulmonary dysplasia for infants ≥32 weeks' gestation: good outcome (alive with no respiratory support) and poor outcome (ongoing respiratory support or death). BNP levels were available at age 1-5 weeks. Longitudinal BNP trends were assessed using mixed-effects modeling. Receiver operating characteristic curves were generated to identify BNP cutoffs maximizing correct outcome classification at each time point. The time to reach BNP cutoff by outcome was assessed using Kaplan-Meier curves for weeks 3-5. RESULTS: Twenty-nine infants (59%) had a poor outcome. Infants with a poor outcome were more likely than those with a good outcome to have liver herniated into the thorax (90% vs 50%; P = .002) and to undergo nonprimary repair (93% vs 35%; P < .001). Mixed-effects modeling demonstrated a differing decline in BNP over time by outcome group (P = .003 for interaction). BNP accurately predicted outcome at 3-5 weeks (area under the curve, 0.81-0.82). BNP cutoffs that maximized correct outcome classification decreased over time from 285 pg/mL at 3 weeks to 100 pg/mL at 4 weeks and 48 pg/mL at 5 weeks. Time to reach the cutoffs of 100 pg/mL and 48 pg/mL were longer in the poor outcome group (log-rank P = .006 and <.0001, respectively). CONCLUSIONS: Elevated BNP accurately predicts poor outcome in infants with CDH at age 3-5 weeks, with declining cutoffs over 3-5 weeks of age.

Ultrasound-guided antecubital vein approach for right heart catheterisation in a Brazilian tertiary centre.

Objective: As a parallel to the radial approach for left heart catheterisation, forearm veins may be considered for the performance of right heart catheterisation. However, data regarding the application of this technique under ultrasound guidance are scarce. The current study aims to demonstrate the feasibility of right heart catheterisation through ultrasound-guided antecubital venous approach in the highly heterogeneous population usually referred for right heart catheterisation. Methods: Data from consecutive right heart catheterisations performed at an academic centre in Brazil, between January 2016 and March 2017 were prospectively collected. Results: Among 152 performed right heart catheterisations, ultrasound-guided antecubital venous approach was attempted in 127 (84%) cases and it was made feasible in 92.1% of those. Yet, there was no immediate vascular complication with the antecubital venous approach in this prospective series. Conclusions: Ultrasound-guided antecubital venous approach for the performance of right heart catheterisation was feasible in the vast majority of cases in our study, without occurrence of vascular complications.

Echocardiographic Measurements of Right Ventricular Mechanics in Infants with Bronchopulmonary Dysplasia at 36 Weeks Postmenstrual Age.

OBJECTIVE: To test the hypothesis that specific echocardiographic measurements of right ventricular (RV) mechanics at 36 weeks postmenstrual age (PMA) are associated with the severity of bronchopulmonary dysplasia (BPD). STUDY DESIGN: A subset of 93 preterm infants (born between 27 and 29 weeks of gestation) was selected retrospectively from a prospectively enrolled cohort. BPD was defined using the National Institutes of Health workshop definition, with modifications for oxygen reduction testing and altitude. The cohort was divided into no-BPD and BPD groups using previously published methodology for analyses. Echocardiographic measurements of RV function (ie, tricuspid annular plane systolic excursion, fractional area of change, systolic-to-diastolic ratio, tissue Doppler myocardial performance index, and RV strain), RV remodeling/morphology (end-systolic left ventricular eccentricity index), and RV afterload (pulmonary artery acceleration time measure) were evaluated at 36 weeks PMA. Multivariable logistic regression determined associations between RV measurements and BPD severity. RESULTS: Compared with the no-BPD cohort, the BPD group had lower birth weight z-scores (P = .04) and trended toward a male predominance (P = .08). After adjusting for birth weight z-score, gestational age, and sex, there were no between-group differences in echocardiographic measurements except for the eccentricity index (scaled OR [0.1-unit increase], 1.49; 95% CI, 1.13-2.12; P = .01). CONCLUSIONS: Among conventional and emerging echocardiographic measurements of RV mechanics, eccentricity index was the sole variable independently associated with BPD severity in this study. The eccentricity index may be a useful echocardiographic measurement for characterizing RV mechanics in patients with BPD at 36 weeks PMA.

Evidence of Echocardiographic Markers of Pulmonary Vascular Disease in Asymptomatic Infants Born Preterm at One Year of Age.

OBJECTIVE: To test the hypothesis that echocardiographic markers of pulmonary vascular disease (PVD) exist in asymptomatic infants born preterm at 1-year corrected age. STUDY DESIGN: We conducted a prospective cohort study of 80 infants born preterm (<29 weeks of gestation) and 100 age- and weight-matched infants born at term and compared broad-based conventional and quantitative echocardiographic measures of pulmonary hemodynamics at 1-year corrected age. Pulmonary artery acceleration time (PAAT), a validated index of pulmonary vascular resistance, arterial pressure, and compliance, was used to assess pulmonary hemodynamics. Lower PAAT is indicative of PVD. Subanalyses were performed in infants with bronchopulmonary dysplasia (BPD, n = 48, 59%) and/or late-onset pulmonary hypertension (n = 12, 15%). RESULTS: At 1 year, there were no differences between conventional measures of pulmonary hypertension in the infants born at term and preterm. All infants born preterm had significantly lower values of PAAT than infants born at term (73 ± 8 milliseconds vs 98 ± 5 milliseconds, P < .001). Infants born preterm with BPD had even lower PAAT than those without BPD (69 ± 5 milliseconds vs 79 ± 4 milliseconds, P < .01). The degree of PVD at 1-year corrected age was inversely related to gestation in all infants born preterm. Data analysis included adjustment for ventricular function and other confounding factors. CONCLUSIONS: In comparison with infants born at term, infants born preterm exhibit abnormal PAAT at 1-year corrected age irrespective of neonatal lung disease status, suggesting the existence of PVD beyond infancy. PAAT measurements offer a reliable, noninvasive tool for screening and longitudinal monitoring of pulmonary hemodynamics in infants.

Cor triatriatum sinister e hipertensão arterial pulmonar secundária em cão / Cor triatriatum sinister and secondary pulmonary arterial hypertension in a dog

This paper describes the occurrence of cor triatriatum sinister, a rare cardiac malformation in dogs, associated with pulmonary edema and pulmonary hypertension in a 5-year-old Poodle female with history of acute dyspnea and cyanosis. The animal presented acute respiratory failure, heart failure with low cardiac output, progressing to acute tubular necrosis and death. The diagnosis was made posmortem due to the clinical instability of the dog. This malformation was diagnosed by the subdivision of the left atrium into two compartments separated by an abnormal fibromuscular membrane, absence of structural abnormalities of the mitral valve and thickening of pulmonary artery tunica media associated with renal tubular degeneration. The occurrence of cor triatriatum in dogs is most common in the right atrium, defined as cor triatriatum dexter. Additionally, pulmonary arterial hypertension associated with this malformation is described only in humans with this heart defect.(AU)

Cor triatriatum sinister e hipertensão arterial pulmonar secundária em cão / Cor triatriatum sinister and secondary pulmonary arterial hypertension in a dog

This paper describes the occurrence of cor triatriatum sinister, a rare cardiac malformation in dogs, associated with pulmonary edema and pulmonary hypertension in a 5-year-old Poodle female with history of acute dyspnea and cyanosis. The animal presented acute respiratory failure, heart failure with low cardiac output, progressing to acute tubular necrosis and death. The diagnosis was made posmortem due to the clinical instability of the dog. This malformation was diagnosed by the subdivision of the left atrium into two compartments separated by an abnormal fibromuscular membrane, absence of structural abnormalities of the mitral valve and thickening of pulmonary artery tunica media associated with renal tubular degeneration. The occurrence of cor triatriatum in dogs is most common in the right atrium, defined as cor triatriatum dexter. Additionally, pulmonary arterial hypertension associated with this malformation is described only in humans with this heart defect.

Capillary hemangiomatosis like-lesions in lung biopsies from children with congenital heart defects.

The morphological findings in the lung vessels of children with pulmonary arterial hypertension associated with uncorrected congenital cardiac shunts may be qualitatively and quantitatively assessed by lung biopsy in selected cases. Among 297 lung biopsies collected over a period of 11 years two cases were detected presenting the typical findings of pulmonary capillary hemangiomatosis, a rare disorder usually associated with pulmonary veno-occlusive disease. We report the clinical and histological findings and discuss about the impact of this unexpected and not-previously described associated lesion on the prognosis and on the therapeutic strategy in patients with pulmonary hypertension associated with congenital heart disease.