Hipertensión pulmonar en los cortocircuitos congénitos

doi:10.1016/S0300-8932(10)70250-5

Revista Española de Cardiología

Volume 63, Issue 10, October 2010, Pages 1179-1193

https://doi.org/10.1016/S0300-8932(10)70250-5 Get rights and content

La hipertensión arterial pulmonar aparece con frecuencia en los pacientes con cardiopatías congénitas. La inmensa mayoría de ellos presentan cortocircuitos cardiacos congénitos. Inicialmente pueden mostrar un cortocircuito izquierda-derecha (sistémico-pulmonar). Su evolución natural muestra que, a medida que progresa la enfermedad, el remodelado y la disfunción vasculares dan lugar a aumentos de la resistencia vascular pulmonar y finalmente se desarrolla un síndrome de Eisenmenger, que es la forma más avanzada. Las anomalías anatomopatológicas y estructurales que se producen en la circulación pulmonar de estos pacientes son, en cierta medida, similares a las que se observan en otras formas de hipertensión arterial pulmonar. Basándose en este conocimiento, el tratamiento del síndrome de Eisenmenger ha sufrido cambios significativos recientemente, con la introducción de los tratamientos dirigidos a abordar las lesiones vasculares pulmonares.

El cierre más temprano de la comunicación cardiaca continúa siendo la mejor prevención de la lesión vascular pulmonar. Sin embargo, los parámetros preoperatorios que indican que una reparación será segura y eficaz continúan sin estar claros, aun cuando la hemodinámica siga siendo la evaluación habitual. La hipertensión pulmonar postoperatoria, tanto en el periodo inmediato tras la reparación quirúrgica como en la evolución a largo plazo, aún es un verdadero reto para el tratamiento. La situación concreta de los ventrículos únicos y la circulación de Fontan plantea también dificultades en presencia de lesiones vasculares pulmonares. Algunos de estos problemas se comentan en este artículo de revisión de la hipertensión pulmonar asociada a cortocircuitos congénitos.

Pulmonary arterial hypertension frequently arises in patients with congenital heart disease. The vast majority present with congenital cardiac shunts. Initially these may manifest as left-to-right (i.e. systemic-to-pulmonary) shunts. The natural history of disease progression involves vascular remodeling and dysfunction that lead to increased pulmonary vascular resistance and, finally, to the development of Eisenmenger's syndrome, which is the most advanced form. The anatomical, pathological and structural abnormalities occurring in the pulmonary circulation of these patients are, to some extent, similar to those observed in other forms of pulmonary arterial hypertension. This understanding has recently led to significant changes in the management of Eisenmenger's syndrome, with the introduction of treatment specifically targeting pulmonary vascular disease.

Early closure of the cardiac shunt remains the best way of preventing pulmonary vascular lesions. However, it is still not clear which preoperative parameters predict safe and successful repair, though hemodynamic evaluation is still routinely used for assessment. Postoperative pulmonary hypertension, both in the immediate period after surgical repair and during long-term follow-up, remains a real therapeutic challenge. The clinical situation of a single ventricle with Fontan circulation also presents difficulties when pulmonary vascular lesions are present. This article reviews pulmonary hypertension associated with congenital shunts and discusses a number of the specific problems encountered.

Section snippets

INTRODUCCIÓN

La hipertensión pulmonar complica la evolución de muchos niños y adultos con cardiopatías congénitas (CPC). El aumento de la presión pulmonar asociado a la CPC es secundario a un aumento del flujo sanguíneo pulmonar o a la elevación de las presiones poscapilares. La hipertensión arterial pulmonar (HAP) se asocia en la inmensa mayoría de los casos a cortocircuitos congénitos.

A pesar de los importantes avances que se han realizado en el conocimiento de la regulación del lecho vascular pulmonar y

EPIDEMIOLOGÍA Y CLASIFICACIÓN

Hay una gran variedad de CPC que pueden conducir a la HAP, pero el grupo más importante es el formado por las lesiones con un cortocircuito izquierda-derecha. Dicho grupo incluye muchos defectos congénitos diferentes que presentan evoluciones diferentes, y ello tiene importancia.

Los avances realizados en cardiología pediátrica y en cirugía han hecho aumentar el número de pacientes con CPC que sobreviven hasta la edad adulta, y han ayudado a prevenir la aparición del SE en muchos pacientes de

Corrección quirúrgica/operabilidad

Los avances realizados en cirugía cardiaca pediátrica permiten actualmente una cirugía correctora de las CPC asociadas a un aumento del flujo sanguíneo pulmonar, que puede aplicarse a una edad muy temprana. Estas intervenciones van destinadas a prevenir toda una serie de secuelas, entre las que se encuentra el desarrollo de una HAP y la EVP. Sin embargo, en algunos pacientes con cortocircuitos izquierda-derecha, estos defectos congénitos pueden pasar inadvertidos hasta una fase avanzada de la

HIPERTENSIÓN PULMONAR PERSISTENTE TARDÍA TRAS LA REPARACIÓN QUIRÚRGICA

El estado funcional y estructural del lecho vascular pulmonar desempeña un papel clave en la forma de presentación y en la evolución de los niños con enfermedades cardiovasculares congénitas. Es el periodo postoperatorio inmediato cuando el niño presenta la máxima vulnerabilidad a un aumento súbito o sostenido de la RVP. Tras la cirugía de una CPC, la reactividad vascular pulmonar aumenta y los estímulos vasospásticos pueden comportar un aumento súbito de la PAP y la resistencia, que dará lugar

TRATAMIENTO DEL SÍNDROME DE EISENMENGER

El SE es la forma más avanzada de HAP asociada a las CPC. Los signos y síntomas de SE suelen deberse a una baja saturación de oxígeno de la sangre y consisten en disnea, cianosis, fatiga, mareo, síncope y arritmias. Los síntomas pueden no aparecer hasta una fase avanzada de la infancia o el inicio de la edad adulta. En general, los pacientes con SE presentan una esperanza de vida reducida, aunque pueden sobrevivir hasta la tercera o la cuarta década de la vida³², y algunos de ellos llegan

CONCLUSIONES

En resumen, las mejoras alcanzadas en el diagnóstico y el tratamiento médico y quirúrgico han modificado las perspectivas de supervivencia a largo plazo en los pacientes con HAP-CPC, y ello ha dado lugar a un aumento significativo del número de pacientes que sobreviven hasta la edad adulta. Aunque existen algunas diferencias en la etiología, la respuesta al tratamiento y la supervivencia, los pacientes pediátricos y adultos con HAP-CPC tienen básicamente la misma enfermedad; un trastorno

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Cited by (30)

Better Outcomes in Pulmonary Arterial Hypertension After Repair of Congenital Heart Disease, Compared With Idiopathic Pulmonary Arterial Hypertension
2021, CJC Open
Citation Excerpt :
The difference in cardiac adaptation between these 2 PAH groups is also supported by the significantly greater brain natriuretic peptide concentration found in idiopathic-PAH patients,9 and may be related to RV conditioning from early childhood in CHD patients.19,22-24 RV adaptation is a major determinant of survival in PAH, and optimizing RV function is a major target for PAH therapies.25-27 Our data confirmed that pediatric patients with idiopathic PAH have a significantly greater mortality rate compared to adults, as previously reported in the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL) in a smaller population.28
Pulmonary vascular changes in postoperative pulmonary artery hypertension (PAH) are similar to those seen in idiopathic PAH. Data are sparse on direct comparative midterm outcomes for these 2 high-risk populations.
Patients with idiopathic or postoperative PAH referred to a large tertiary hospital between June 2005 and July 2019 were retrospectively evaluated.
A total of 364 consecutive patients were studied, including 201 postoperative PAH patients and 163 patients with idiopathic PAH, with a median age of 18.7 (interquartile range 10.0, 31.5) and 7.3 (IQR: 2.9, 18.3) years, respectively. PAH-specific drugs were used in 77.7% of patients; 31.4% received combination therapy. Patients with idiopathic PAH had a shorter 6-mintue walk distance, lower percutaneous oxygen saturation, and higher B-type natriuretic peptide levels than those with postoperative PAH at diagnosis (all P < 0.001), During a median follow-up time of 3.4 (interquartile range: 2.1, 5.8) years, 56 patients (15.4%) died, and one underwent bilateral lung transplantation. Patients with postoperative PAH had better survival than those with idiopathic PAH, according to age (hazard ratio [HR] 0.128, 95% confidence interval [CI]: 0.07-0.22, P < 0.0001); Kaplan–Meier survival estimates at 5 years for idiopathic and postoperative PAH patients were 74.3% and 92.6%, respectively. Patients in New York Heart Association functional class III–IV had an over 4-fold increased risk of death (HR 4.85, 95% CI: 2.61-9.00, P < 0.0001). Patients < 18 years of age at idiopathic PAH diagnosis had a worse survival compared to adult patients (HR 6.90, 95% CI: 4.19-15.56, P = 0.040).
Postoperative-PAH patients had better midterm survival compared to patients with idiopathic PAH. Mortality was significant in both PAH groups, reinforcing the need for early diagnosis and optimal individualized management to improve outcomes.
Les changements vasculaires pulmonaires associés à l'hypertension artérielle pulmonaire (HAP) postopératoire sont semblables à ceux observés dans l'HAP idiopathique. On dispose de peu de données comparatives directes sur les résultats à moyen terme dans ces deux populations à risque élevé.
Les patients présentant une HAP idiopathique ou postopératoire qui avaient été dirigés vers un important centre hospitalier de soins tertiaires entre juin 2005 et juillet 2019 ont fait l'objet d'une évaluation rétrospective.
Au total, 364 patients consécutifs ont été étudiés, dont 201 cas d'HAP postopératoire et 163 cas d'HAP idiopathique, dont l'âge médian était de 18,7 (intervalle interquartile : de 10,0 à 31,5) et de 7,3 (intervalle interquartile : de 2,9 à 18,3) ans, respectivement. Des médicaments traitant précisément l'HAP avaient été utilisés chez 77,7 % des patients; 31,4 % des patients avaient reçu un traitement en association. Chez les patients présentant une HAP idiopathique, la distance parcourue au test de marche de six minutes était inférieure, la saturation percutanée en oxygène était inférieure et les taux de peptide natriurétique de type B étaient supérieurs aux valeurs affichées par les patients présentant une HAP postopératoire au diagnostic (toutes les valeurs p < 0,001). Pendant une période de suivi d'une durée médiane de 3,4 (intervalle interquartile : de 2,1 à 5,8) ans, 56 patients (15,4 %) étaient décédés, et un patient avait subi une transplantation pulmonaire bilatérale. La survie des patients présentant une HAP postopératoire était supérieure à celle des patients avec une HAP idiopathique, en fonction de l'âge (rapport des risques instantanés [RRI] 0,128, intervalle de confiance à 95 % [IC] : de 0,07 à 0,22, p < 0,0001); la survie à cinq ans des patients atteints d'HAP idiopathique et postopératoire, estimée selon la méthode de Kaplan-Meier, était de 74,3 % et de 92,6 %, respectivement. Chez les patients appartenant aux classes fonctionnelles III et IV de la New York Heart Association, le facteur multiplicatif du risque de décès était plus de quatre fois supérieur (RRI 4,85, IC à 95 % : de 2,61 à 9,00, p < 0,0001). Les patients âgés de moins de 18 ans au moment du diagnostic d'HAP idiopathique avaient un taux de survie inférieur à celui des patients adultes (RRI 6,90, IC à 95 % : de 4,19 à 15,56, p = 0,040).
La survie à moyen terme des patients atteints d'une HAP postopératoire était supérieure à celle des patients dont l'HAP était idiopathique. La mortalité était importante dans les deux groupes d'HAP, ce qui met en lumière la nécessité d'un diagnostic précoce et d'une prise en charge individualisée optimale afin d'améliorer les résultats.
Congenital Heart Disease-Associated Pulmonary Hypertension
2021, Clinics in Chest Medicine
Citation Excerpt :
Data should be obtained in the absence of respiratory or metabolic acidosis, hypoxia, anemia, or agitation. Nevertheless, the issue of determining operability is not straightforward and has been highlighted in several recent articles.14,22–24 Lopes and O’Leary25 proposed the following hemodynamic criteria for operability based on existing literature and surveying centers of excellence with experience in the treatment of pulmonary hypertensive patients: baseline PVRi less than 6 WUm2 and PVR:SVR ratio less than 0.3.
Pulmonary hypertension
2018, Critical Heart Disease in Infants and Children
Pulmonary hypertension is a formidable challenge to the care of children with congenital heart disease, with a burgeoning incidence in the perioperative period. Awareness of this problem, prospective clinical pathway development, and focused expertise are all needed to optimally equip multidisciplinary teams to meet this challenge. Here we present insights into epidemiology, costs, anatomy, pathophysiology, medical diagnostics, and pharmacotherapies involved in treating pulmonary hypertension in pediatric congenital heart disease patients. The emphasis is on identifying patients at risk, choosing appropriate diagnostics, optimizing perioperative outcomes, timely recognition and management of pulmonary hypertensive crisis, the molecular basis of pharmacotherapy, and guidelines for treatment. Anticipatory guidance is also provided for transferring children from hospital to home, and frontiers of research in the field are considered.
Relation of Cytokine Profile to Clinical and Hemodynamic Features in Young Patients With Congenital Heart Disease and Pulmonary Hypertension
2017, American Journal of Cardiology
In congenital heart disease, severity of pulmonary hypertension and operability is defined by noninvasive parameters (clinical history, physical examination, and echocardiography) and sometimes, cardiac catheterization. We investigated how circulating levels of inflammatory mediators correlate with such parameters in a young pediatric population (age, 2.0 months to 3.1 years) and the effects of preoperative pulmonary vasodilator therapy with sildenafil. Cytokines were analyzed in serum using chemiluminescence signals. In the whole patient group (n = 47), interleukin 17E, a Th2 immune response mediator increased with increasing age, considered as a parameter of disease severity (R² = 0.24, p <0.001), whereas the angiogenic chemokine growth-regulated oncogene alpha decreased (R² = 0.21, p = 0.001). Macrophage migration inhibitory factor chemokine was greater in subjects with elevated pulmonary vascular resistance (n = 16, p = 0.022), whereas regulated on activation, normal T cell expressed and secreted chemokine was greater in subjects with pulmonary congestion due to increased pulmonary blood flow (n = 31, p = 0.037). The observations were the same for the specific subpopulation of patients with Down syndrome (p = 0.009 and p = 0.012 for migration inhibitory factor and regulated on activation, normal T cell expressed and secreted in the respective subgroups). Sildenafil administration to patients with elevated pulmonary vascular resistance resulted in improvement of pulmonary blood flow (p = 0.012) and systemic oxygen saturation (p = 0.010), with a decrease in serum interleukin 6 (p = 0.027) and soluble ICAM-1 (p = 0.011). In conclusion, levels of circulating inflammatory molecules seem to correlate with disease severity in this population, with potential pathophysiological and therapeutic implications.
Elevated serum HMGB1 in pulmonary arterial hypertension secondary to congenital heart disease
2016, Vascular Pharmacology
Citation Excerpt :
Eligible patients were divided into three groups according to mean pulmonary arterial pressure [5], including CHD with mild-to-moderate PAH (25 mm Hg ≤ MPAP < 45 mm Hg, n = 23), CHD with severe PAH (MPAP ≥ 45 mm Hg, n = 60), and CHD without PAH (all with left-to-right shunting and MPAP < 25 mm Hg, n = 23) group. CHD with severe PAH group was further divided into three sub-groups according to the pulmonary vascular resistance (PVR) and Qp/Qs measurements: PAH patients with low pulmonary vascular resistance (PVR < 10 wood units), preEisenmenger (PVR > 10 wood units, 1.0 < Qp/Qs < 1.5), and Eisenmenger's syndrome (ES, PVR > 10 wood units, Qp/Qs < 1.0, with cyanosis) [13,14]. Routine cardiac catheterization and hemodynamic measurements were performed with intravenous midazolam sedation.
This study investigated the potential value of serum high mobility group box-1 (HMGB1) level in the diagnosis, staging and treatment response of patients with pulmonary arterial hypertension secondary to congenital heart disease (PAH-CHD).
This was a single-center prospective study in 106 CHD patients. Serum HMGB1 levels were measured by enzymelinked immunosorbent assay. HMGB1 levels were significantly increased in patients with PAH compared to patients without PAH (P < 0.01) and healthy controls (P < 0.001). HMGB1 levels significantly correlated with pulmonary arterial pressure (P < 0.001) and pulmonary vascular resistance (PVR) (P < 0.001). In patients with severe PAH, HMGB1 levels were significantly higher in patients with Eisenmenger syndrome (ES) than in patients exhibiting low PVR (P < 0.001). Severe PAH and ES was identified by serum HMGB1 with a cutoff value of 13.62 ng/mL (P < 0.001) with a specificity of 82.8% and a sensitivity of 90%, and a cutoff value of 21.62 ng/mL (P = 0.001) with a specificity of 85.2% and a sensitivity of 64.3%, respectively. HMGB1 levels were significantly decreased after sildenafil therapy for 6 months (P < 0.01).
Our study suggests that serum HMGB1 level may be used as a biomarker to identify PAH in CHD patients, assess pulmonary vascular remodeling, and evaluate the treatment response to sildenafil.
BMPR2 mutation is a potential predisposing genetic risk factor for congenital heart disease associated pulmonary vascular disease
2016, International Journal of Cardiology
Citation Excerpt :
It is estimated that worldwide 3 million children are at risk for the development of pulmonary vascular disease due to congenital heart disease [3]. Early closure of the cardiac shunt remains the best way of preventing pulmonary vascular lesions [4]. However, it is still not clear which preoperative parameters predict safe and successful repair, though hemodynamic evaluation is still routinely used for assessment.
Pulmonary arterial hypertension (PAH) frequently arises in patients with congenital heart disease (CHD) and can lead to pulmonary vascular disease (PVD). The present study was initiated to distinguish the predisposing effect of bone morphogenetic protein receptor 2 (BMPR2) in CHD by comparing the different mutation features of BMPR2 between CHD patients with or without PVD.
294 CHD–PVD and 161 CHD without PVD patients were enrolled. PAH was diagnosed by heart catheterization at rest after CHD was first recognized by echocardiography. PVD was defined as a pulmonary vascular resistance (PVR) more than 3 Wood units. BMPR2 gene was screened by direct sequencing. A total of 24 mutations were identified, accounting for 22 of the 294 patients with CHD–PVD (7.5%) and 2 of the 161 CHD patients without PVD (1.2%, P = 0.004). Female/male CHD–PVD patient ratio was 1.6:1, while in the BMPR2 mutation carriers female patients were more dominant (4.5:1, P = 0.042). A significant higher BMPR2 mutation rate (12.6%) was found in repaired CHD–PVD (P = 0.010). BMPR2 mutations in CHD–PVD patients were identified in different clinical phenotypes. Missense mutation of BMPR2 is the dominant mutation type.
Genetic predisposing factor may be an important component in the process of development of PVD in CHD patients. Female, repaired patients are more likely to be detected with genetic mutations.

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PUESTA AL DÍA Corazón derecho y circulación pulmonar (X)Hipertensión pulmonar en los cortocircuitos congénitosPulmonary Hypertension in Congenital Shunts

Section snippets

INTRODUCCIÓN

EPIDEMIOLOGÍA Y CLASIFICACIÓN

Corrección quirúrgica/operabilidad

HIPERTENSIÓN PULMONAR PERSISTENTE TARDÍA TRAS LA REPARACIÓN QUIRÚRGICA

TRATAMIENTO DEL SÍNDROME DE EISENMENGER

CONCLUSIONES

J Am Coll Cardiol

Int J Cardiol

J Am Coll Cardiol

Am J Cardiol

J Am Coll Cardiol

Int J Cardiol

Int J Cardiol

Int J Cardiol

J Thorac Cardiovasc Surg

J Am Coll Cardiol

J Am Coll Cardiol

Int J Cardiol

Am J Cardiol

Int J Cardiol

Am Heart J

Int J Cardiol

Int J Cardiol

Int J Cardiol

Am J Cardiol

J Heart Lung Transplant

Prog Cardiovasc Dis

Ann Thorac Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Ann Thorac Surg

Eur Heart J

Fontan and the pulmonary circulation: a potential role for new pulmonary hypertension therapies

Heart

Management of pulmonary arterial hypertension associated with congenital systemic-to-pulmonary shunts and Eisenmenger's syndrome

Drugs

Congenital heart disease and pulmonary hypertension

Rev Port Cardiol

Pulmonary hypertension associated with congenital cardiac disease

Cardiol Young

Classifying pulmonary hypertension in the setting of the congenitally malformed heart—cleaning up a dog's dinner

Cardiol Young

Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology

Eur Heart J

Assessment of operability of congenital cardiac shunts with increased pulmonary vascular resistance

Catheter Cardiovasc Interv

Measurement, interpretation and use of haemodynamic parameters in pulmonary hypertension associated with congenital cardiac disease

Cardiol Young

Treatment and survival in children with pulmonary arterial hypertension: the UK Pulmonary Hypertension Service for Children 2001-2006

Heart

Preoperative pulmonary hemodynamics and assessment of operability: is there a pulmonary vascular resistance that precludes cardiac operation?

Pediatr Crit Care Med

Pulmonary vascular disease in different types of congenital heart disease

Br Heart J

Is lung biopsy useful for surgical decision making in congenital heart disease?

Eur J Cardiothorac Surg

Inhaled nitric oxide as a preoperative test (INOP Test I): the INOP Test Study Group

Circulation

PUESTA AL DÍA Corazón derecho y circulación pulmonar (X)
Hipertensión pulmonar en los cortocircuitos congénitosPulmonary Hypertension in Congenital Shunts