Improvement in Echocardiographic and Diagnostic Biomarkers after Systemic Glucocorticoid Therapy in Infants with Pulmonary Hypertension.

OBJECTIVE: To assess the effect of treating pulmonary hypertension (PH) in infants younger than 1 year of age with systemic glucocorticoids while using echocardiographic and diagnostic biomarkers as measures of efficacy. STUDY DESIGN: A retrospective chart review was performed on 17 hospitalized infants younger than 1 year of age at St Louis Children's Hospital who received a 5- to 7-day course of systemic glucocorticoid treatment followed by a 3-week taper with no significant intracardiac shunts from January 1, 2017, to December 31, 2021. Quantitative echocardiographic indices for PH, N-terminal pro b-type natriuretic peptide, and/or b-type natriuretic peptide levels were collected before glucocorticoid treatment, after the glucocorticoid burst, and after the 21-day taper. RESULTS: Mean (±SD) gestational age was 32.1 (±5.8) weeks, 5 infants were (29%) concomitantly treated with sildenafil, and 8 were male. Twelve were classified as World Health Organization group 3 PH (71%) and 5 as World Health Organization group 1 PH. There were significant improvements 30 days after glucocorticoid initiation in b-type natriuretic peptide levels (P = .008), PCO2 (P = .03), eccentricity index (P = .005), right ventricular ejection time (P = .04), pulmonary artery acceleration time (P = .002), and pulmonary artery acceleration time-to-right ventricular ejection time ratio (P = .02). Tricuspid regurgitation velocity was not able to be assessed. There were no mortalities during the study timeline. CONCLUSIONS: In our retrospective study, systemic glucocorticoid therapy was well tolerated and appeared to be associated with significant improvement in cardiopulmonary function in infants with PH. Further prospective study in a larger sample is warranted.

Shape of Pulmonary Artery Doppler Flow Profile and Right Ventricular Hemodynamics in Neonates.

OBJECTIVES: To characterize pulmonary artery Doppler flow profile (PAFP) patterns among infants receiving care in neonatal intensive care units and to examine the association of PAFP patterns with pulmonary and right ventricular (RV) hemodynamics. STUDY DESIGN: This is a retrospective study at 2 tertiary intensive care units over 4 years that included neonates who demonstrated a complete tricuspid regurgitation envelope on targeted neonatal echocardiography. Separate personnel reviewed TNEs to characterize PAFP patterns, divide cohort into PAFP groups, and measure quantitative indices of RV hemodynamics (RV systolic pressure, pulmonary artery acceleration time and its ratio with RV ejection time, tricuspid annular plane systolic excursion, and RV output), for intergroup comparisons. RESULTS: We evaluated TNEs from 186 neonates with median gestational age of 28.5 weeks (IQR, 25.9-35.9 weeks). Four distinct PAFP patterns were identified (A) near-isosceles triangle (22%), (B) right-angled triangle (29%), (C) notching (40%), and (D) low peak velocity (<0.4 m/s; 9%). Groups A-C demonstrated a stepwise worsening in all indices of PH, whereas pattern D was associated with lower tricuspid annular plane systolic excursion and RV output. Using common definitions of pulmonary hypertension (PH), pattern A performed best to rule out PH (sensitivity range, 81%-90%) and pattern C for diagnosing PH (specificity range, 63%-78%). CONCLUSIONS: Inspection of PAFP is a simple bedside echocardiography measure that provides clinically meaningful information on underlying RV hemodynamics and may aid in screening and monitoring of patients for PH in intensive care units.

Accuracy of Transthoracic Echocardiogram as a Screening Method in the Clinical Practice of Pulmonary Hypertension Investigation. / Acurácia do Ecocardiograma Transtorácico como Método de Triagem na Prática Clínica da Investigação da Hipertensão Pulmonar.

BACKGROUND: The transthoracic echocardiogram (TTE) plays a screening role in the diagnostic algorithm of pulmonary hypertension (PH). Studies have shown a significant disagreement between TTE measurements of the systolic pulmonary artery pressure (sPAP) and right atrial pressure (RAP) and those obtained by right heart catheterization (RHC). OBJECTIVE: To compare TTE measurements of sPAP and RAP with those obtained by RHC in patients being investigated for PH. METHODS: Patients referred to a PH reference center with a high or intermediate TTE probability of PH upon admission were submitted to RHC. The agreement between sPAP and RAP from both procedures was assessed through the Bland-Altman test. Differences of up to 10 mmHg for sPAP and 5 mmHg for RAP were considered within the variability of the test. Receiver Operating Characteristic (ROC) curve was constructed to determine the most accurate sPAP and Tricuspid regurgitation maximal velocity (TRV)values associated with the diagnosis of PH by RHC. The adopted level of statistical significance was 5%. RESULTS: Ninety-five patients were included. The Bland-Altman analysis showed a bias of 8.03 mmHg (95% CI:-34.9-50.9) for sPAP and -3.30 mmHg (95% CI:-15.9-9.3) for RAP. AUC for sPAP and TRV measured by TTE for discrimination of probable PH were 0.936 (95% CI: 0.836-1.0) and 0.919 (95% CI: 0.837-1.0), respectively. However, only 33.4% of the echocardiographic estimate of sPAP and 55.1% of RAP were accurate, as compared to the measurements obtained by RHC. CONCLUSION: TTE has a high discriminatory power as a screening diagnostic method for PH despite presenting disagreements between sPAP and RAP absolute values when compared to RHC measurements.

FUNDAMENTO: O ecocardiograma transtorácico (ETT) tem um papel de triagem no algoritmo diagnóstico da hipertensão pulmonar (HP). Estudos demonstraram uma discordância significativa entre as medições do ETT da pressão arterial pulmonar sistólica (PAPs) e da pressão atrial direita (PAD) e as obtidas pelo cateterismo do coração direito (CCD). OBJETIVO: Comparar as medições do ETT da PAPs e da PAD com as obtidas pelo CCD em pacientes com suspeita de HP. MÉTODOS: Pacientes encaminhados a um centro de referência com probabilidade alta ou intermediária de PH ao ETT na admissão hospitalar passaram por CCD. A concordância entre a PAPs e a PAD em ambos os procedimentos foi avaliada pelo teste de Bland-Altman. Diferenças de até 10 mmHg na PAPs e de até 5 mmHg na PAD foram consideradas dentro da variabilidade do teste. A curva de característica de operação do receptor (ROC) foi construída para determinar os valores mais precisos de PAPs e VRT associados ao diagnóstico de HP pelo CCD. O nível de significância estatística adotado foi 5%. RESULTADOS: Foram incluídos noventa e cinco pacientes. A análise de Bland-Altman análise revelou um viés de 8,03 mmHg (IC 95%: -34,9 a 50,9) na PAPs e -3,30 mmHg (IC 95%: -15,9 a 9,3) na PAD. AUC da PAPs e VRT medidas pelo ETT para a discriminação de provável HP foram de 0,936 (IC 95%: 0,836 a 1,0) e 0,919 (IC 95%: 0,837 a 1,0), respectivamente. Entretanto, apenas 33,4% da estimativa ecocardiográfica da PAPs e 55,1% da PAD foram precisas, em comparação às medições obtidas pelo CCD. CONCLUSÃO: O ETT tem um alto poder discriminatório como método diagnóstico de triagem para HP, apesar de apresentar discordâncias entre os valores absolutos de PAPs e PAD, em comparação às medições por CCD.

Accuracy of echocardiography and chest tomography for pulmonary hypertension screening in patients awaiting lung transplantation.

OBJECTIVE: To examine the accuracy of a pulmonary hypertension screening strategy based on a combination of echocardiographic data and tomographic measurements (pulmonary artery diameter and pulmonary artery diameter to ascending aorta diameter ratio) in patients with chronic lung disease referred for lung transplantation. METHODS: A retrospective observational study with patients with pulmonary emphysema or fibrosis referred for transplantation between 2012 and 2016. Pulmonary hypertension was defined as mean pulmonary artery pressure ≥25mmHg, or between 21 and 24mmHg, with pulmonary vascular resistance >3 Wood units on right heart catheterization. Tomographic measurements were made by two independent radiologists. RESULTS: This sample comprised 13 patients with emphysema and 19 patients with pulmonary fibrosis. Of these, 18 had pulmonary hypertension. The level of agreement in tomographic measurements made by radiologists was high (intraclass correlation coefficients 0.936 and 0.940, for pulmonary artery diameter and pulmonary artery diameter to ascending aorta diameter ratio, respectively). Areas under the ROC curves constructed for pulmonary artery diameter, pulmonary artery diameter to ascending aorta diameter ratio, and pulmonary artery systolic pressure as predictors of pulmonary hypertension were 0.540, 0.629 and 0.783, respectively. The sensitivity, specificity and negative predictive value of pulmonary artery systolic pressure ≥40mmHg were 67%, 79% and 65%, respectively. The combined criterion (pulmonary artery diameter to ascending aorta diameter ratio >1 and/or pulmonary artery systolic pressure ≥40mmHg) achieved sensitivity of 72%, specificity of 79%, and a negative predictive value of 69%. CONCLUSION: Measurements of pulmonary artery and ascending aorta diameter were highly reproducible. The association of pulmonary artery and aortic diameter >1 and/or pulmonary artery systolic pressure ≥40mmHg improved the sensitivity and the negative predictive value for pulmonary hypertension screening. This strategy demands prospective validation to assess safety and cost-effectiveness.

Magnetic Resonance Imaging Assessment of Pulmonary Vascularity in Infants with Congenital Diaphragmatic Hernia: A Novel Tool for Direct Assessment of Severity of Pulmonary Hypertension and Hypoplasia.

OBJECTIVES: To assess the feasibility of magnetic resonance imaging (MRI) for postnatal assessment of pulmonary vascularity in infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: Infants with prenatally diagnosed CDH (n = 24) received postnatal pulmonary MRI. Infants with nonpulmonary birth defects served as controls (n = 5). Semiautomatic segmentation was performed to obtain total vascular volume using time of flight images to assess vascularity. RESULTS: Average vascular density (vascular volume/lung volume) in control infants was 0.23 ± 0.06 mm3/mm3 compared with 0.18 ± 0.06 mm3/mm3 in infants with CDH is (P = .09). When stratified further based on CDH severity, the difference between control infants and moderate CDH group was statistically significant. (0.23 mm3/mm3 vs 0.15 mm3/mm3, P = .01). Ipsilateral vascular density on MRI in infants with CDH significantly correlated with the prenatal pulmonary hypertensive index (P = .0004, Spearman R = +0.87) and with number of days on mechanical ventilation (P = .04, Spearman R = -0.44), total days on inhaled nitric oxide (P = .02, Spearman R = -0.47), use of epoprostenol for acute pulmonary hypertension (PH) (0.14 mm3/mm3 vs 0.20 mm3/mm3, P = .005), and use of sildenafil for chronic PH (0.15 mm3/mm3 vs 0.19 mm3/mm3, P = .03). CONCLUSIONS: Our results suggest that postnatal pulmonary vascularity assessed by MRI strongly correlates with prenatal and postnatal markers of PH severity and that pulmonary vascularity may serve as a direct measure of pulmonary vascular hypoplasia in infants with CDH.

[Reentry High-Altitude Pulmonary Edema in Pediatric Patients]. / Edema pulmonar de altura por re-ascenso en pacientes pediátricos.

INTRODUCTION: High-altitude pulmonary edema (HAPE) occurs when a person without adequate pulmonary adap tation ascends above 2500 meters above sea level. Usually, it is more frequent among those living at low altitudes, however, it can occur in people who live at high altitudes and descend to lower ones for a short time, which is called re-entry HAPE. OBJECTIVE: To describe the clinical course, diagnosis, and management of re-entry HAPE in pediatric patients, and to achieve an early approach to reduce complications. CLINICAL CASES: We present 6 cases of pediatric patients diagnosed with re-entry HAPE in a fourth level hospital in Bogotá, Colombia, between 2013 and 2018. All patients resided in Bogo tá, 5/6 were male, the median age was 11 years, 4/6 had a history of lung disease, and 5/6 required a high-flow oxygen device. In all cases, the chest X-ray reported opacities and 2/6 showed pulmonary hypertension on the echocardiogram. All patients were initially treated for bacterial pneumonia or asthma and, although they progressed adequately, these inadequate treatments can cause compli cations. CONCLUSION: The diagnosis, treatment, and prevention of HAPE are important since it is usually confused with infectious pulmonary pathologies due to its similar clinical course, which leads to inadequate treatment and can generate complications. The suggestion is that HAPE should be con sidered as a differential diagnosis in patients with a recent history of ascending to high altitude cities.

Coexistent Mitral Stenosis and left Circumflex Coronary Artery to left Atrial Fistula in a Patient with Severe Pulmonary Hypertension.

Coronary artery to left atrial fistula is rare in patients with mitral stenosis. We report an interesting case of a patient with concomitant mitral valve stenosis and coronary fistulae, originating from the left circumflex artery and drained into the left atrium with two terminal orifices.

Coexistent mitral stenosis and left circumflex coronary artery to left atrial fistula in a patient with severe pulmonary hypertension

Abstract Coronary artery to left atrial fistula is rare in patients with mitral stenosis. We report an interesting case of a patient with concomitant mitral valve stenosis and coronary fistulae, originating from the left circumflex artery and drained into the left atrium with two terminal orifices.

Mixoma auricular izquierdo gigante que causa obstrucción valvular mitral, hipertensión pulmonar y tromboembolia pulmonar / Giant atrial myxoma causing mitral valve obstruction, pulmonary hypertension and pulmonary thromboembolism

Resumen: Los tumores cardíacos pueden ser primarios o, más frecuentemente secundarios o metastásicos. Entre los tumores primarios es más frecuente el mixoma, cuya ubicación más común es en la aurícula izquierda. Las manifestaciones clínicas son diversas, producidas principalmente por obstrucción mecánica, embolizaciones, y manifestaciones constitucionales. Se comunica el caso de un paciente de 32 años, con cuadro clínico de insuficiencia cardíaca, hipertensión pulmonar severa y tromboembolismo pulmonar bilateral. Se hizo el diagnóstico de mixoma auricular izquierdo. Se resecó el tumor y se manejó la hipertensión pulmonar desde el ingreso al hospital con inhibidores de la fosfodiesterasa asociado a anticoagulación. Se discute el tema dando énfasis a aspectos fisiopatológicos involucrados tanto en la hipertensión pulmonar como en la presencia de tromboembolia pulmonar.

Abstract: Cardiac tumors may be primary or, more frequently secondary or associated to metastasis. Atril myxoma es the most frequent primary tumor, usually located in the left atrium. Clinical manifestations include those due to mitral valve occlusión, emboli and general non spedific symptoms and signs. Herein we report the clinical case of a 32 year old patient with severe pulmonary hypertension and bilateral pulmonary embolism. The tumor was extirpated, and he received phosphoro-diesterase inhiborts and anticoagulants. Subsequent clinical course was satisfactory. A brief discussion of this condicion is included.

Impact of right ventricular work and pulmonary arterial compliance on peak exercise oxygen uptake in idiopathic pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is associated with increased right ventricular (RV) afterload, RV dysfunction and decreased peak oxygen uptake (pVO2). However, the pulmonary hemodynamic mechanisms measured by exercise right heart catheterization (RHC) that contribute to reduced pVO2 in idiopathic PAH (IPAH) are not completely characterized. Therefore, we sought to evaluate the exercise RHC determinants of pVO2 in patients with IPAH. METHODS: 519 consecutive patients with suspected and/or confirmed pulmonary hypertension were prospectively screened to identify 20 patients with IPAH. All IPAH patients were prospectively evaluated with resting and exercise RHC and cardiopulmonary exercise testing. RESULTS: 85% of the patients were female; the median age was 34[29-42] years old. At peak exercise, mean pulmonary arterial (PA) pressure was 76 ± 17 mmHg, PA wedge pressure was 14 ± 5 mmHg, cardiac output (CO) was 5.7 ± 1.9 L/min, pulmonary vascular resistance was 959 ± 401 dynes/s/cm5 and PA compliance was 0.9[0.6-1.2] ml/mmHg. On univariate analysis, pVO2 positively correlated to peak CO, peak cardiac index, peak stroke volume index, peak RV stroke work index (RVSWI) and peak oxygen saturation. There was a negative correlation between pVO2 and Δ (rest to peak change) PA compliance. In age-adjusted multivariate model, peak RVSWI (Coefficient = 0.15, Beta = 0.63, 95% CI [0.07-0.22], p < 0.01) and ΔPA compliance (Coefficient = -2.51, Beta = -0.43, 95% CI [-4.34-(-0.68)], p = 0.01) had the best performance predicting pVO2 (R2 = 0.66). CONCLUSIONS: In conclusion, a load dependent measurement of RV function (RVSWI) and the pulsatile component of RV afterload (ΔPA compliance) significantly influence pVO2 in IPAH, further highlighting the pivotal role of hemodynamic coupling to IPAH exercise capacity.

Echocardiographic evaluation of pulmonary hypertension, right ventricular function, and right ventricular-pulmonary arterial coupling in patients with rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) patients are at increased risk for developing cardiovascular disease, including right heart failure. The evaluation of right ventricle (RV) using the relationship between tricuspid annular plane systolic excursion (TAPSE) and right ventricular systolic pressure (RVSP) is of clinical prognostic relevance. Mild echocardiographic pulmonary hypertension (ePH) has been associated with worse RV function. The aim of this study was to evaluate RV function as measured by TAPSE to RVSP ratio in rheumatoid arthritis patients compared to matched healthy controls. METHOD: A case-control study with 67 RA patients aged 40 to 75 years that fulfilled the 2010 ACR/EULAR criteria and 45 matching controls was included. A transthoracic echocardiogram was performed to all patients. TAPSE was measured as the distance traveled from end-diastole to end-systole. RVSP was calculated using the modified Bernoulli equation. Comparisons were done using Chi-square and Mann-Whitney's U test or Student's t test. RESULTS: Patients with RA had significantly reduced ventricular function (TAPSE 23 [21-25] vs 25 [23-26], p = 0.033) and TAPSE/RVSP ratio was significantly lower in RA-patients than controls (TAPSE to RVSP ratio 0.809 [0.67-1.01] vs 0.933 [0.79-1.11], p = 0.009). RA-patients with mild ePH had similar RV function, evaluated by TAPSE, in comparison to RA-patients with normal RVSP. CONCLUSION: RA-patients had worse RV function measured by TAPSE and worse TAPSE/RVSP ratio than controls. Also, RA-patients with mild ePH had reduced right ventricular-pulmonary arterial coupling in comparison with patients with RA and normal RVSP. These echocardiographic findings could justify aggressive treatment for these patients and assess their evolution. Key Points • Right ventricular (RV) function and RV coupling with the pulmonary artery (RV-PA coupling) were worse in patients with RA in comparison to healthy controls. • Values of right ventricular systolic pressure (RVSP) were similar between RA-patients and non-RA controls. • Prevalence of normal RVSP, mild echocardiographic pulmonary hypertension (ePH), and pulmonary hypertension was similar between RA-patients and non-RA matched controls •Patients with RA and mild ePH had reduced RV-PA coupling in comparison with RA-patients with normal RVSP.

Interplay Between Thyroid Hormone Status and Pulmonary Hypertension in Graves' Disease: Relevance of the Assessment in Thyrotoxic and Euthyroid Patients.

Background: Graves' disease (GD) is the most common cause of hyperthyroidism and can cause cardiac changes, such as pulmonary hypertension. Methods: This is a prospective study in which we obtained demographic, clinical, laboratory data and characteristics of the GD, in addition to investigating cardiorespiratory function, focusing on the detection of pulmonary hypertension. Patients were separated into two groups: thyrotoxicosis and euthyroidism. Ninety patients with GD of both sexes, over 18 years of age, were included. The cardiorespiratory assessment included an echocardiographic evaluation, a questionnaire of specific symptoms, spirometry and a six-minute walk test. Results: The hyperthyroid group included 42 patients (47.73%) and the euthyroid group 46 patients (52.27%); 78 were women (86.67%). The prevalence of pulmonary hypertension between the hyperthyroidism (48.57%) and the euthyroidism (29.41%) groups was not different. Free thyroxine levels (FT4) (OR 1.266), higher left atrium volume (OR 1.113) and right ventricle diameter were associated with pulmonary hypertension. A direct correlation between FT4 with forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1), as also an inverse correlation between initial oxygen saturation (SpO2) with diagnostic time and drop SpO2 with the ratio between the diastolic velocity E of the mitral flow and the diastolic velocity of the mitral ring (E/e') were observed in the euthyroid group. An inverse correlation between FT4 levels with walked distance as % of predicted value, and a direct correlation between E/e' ratio and walked distance as % of predicted value were observed in the hyperthyroid group. Conclusion: We emphasize the importance of a cardiorespiratory reassessment in GD, even after a long-term control of the thyrotoxic state, as we demonstrate that about 30% of these patients remain with PH and are subject to specific treatment.

Mid-term follow-up of balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension: An experience in Latin America.

OBJECTIVES: To describe the characteristics of patients who undergo balloon pulmonary angioplasty (BPA) for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) and report the mid-term outcomes. BACKGROUND: BPA has been recently introduced in Latin America. Mid-term results have not been published. METHODS: Prospective Chilean Registry of inoperable CTEPH patients who underwent BPA. Clinical variables were analyzed at baseline, after each procedure and at follow-up. Hemodynamic variables were recorded before and after the last BPA. RESULTS: Between August 2016 and September 2019, 22 patients (17 women), 59 ± 12.7 years, underwent 81 BPA and were followed for as long as 33.1 months (mean 17.3 ± 7.5). Mean pulmonary artery pressure decreased by 17.4% (51.1 ± 12 vs. 42.2 ± 13 mmHg, p = .001), pulmonary vascular resistance by 23.9% (766.7 ± 351 vs. 583 ± 346 dynes/s/cm-5 , p = .001), cardiac index increased by 8% (2.3 ± 0.54 vs. 2.5 ± 0.54 L/min/m2 , p = .012), N-terminal pro-B-type natriuretic peptide decreased by 73.8% (1,685 ± 1,045 vs. 441.8 ± 276 pg/dl, p = .006), and 6-min walk distance improved by 135 m (316.7 ± 94 vs. 451.1 ± 113 m, p = .001). One patient (4.5%) developed lung reperfusion injury and four patients (18.2%) had minor bleeding (hemoptysis), after the procedure. There was no mortality associated with BPA. CONCLUSIONS: Our results confirm that BPA for inoperable CTEPH is a relatively safe procedure that improves clinical and hemodynamic parameters in the mid-term. This therapy should be considered as an alternative, mainly in places where access to PAH therapy or surgery is restricted.