Enri Leci

Current era survival of patients with pulmonary arterial hypertension associated with congenital heart disease: a comparison between clinical subgroups

AIMS This study compared the clinical, functional, and haemodynamic characteristics and current era survival of subgroups of patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD): Eisenmenger syndrome (ES); PAH-CHD associated with systemic-to-pulmonary shunts (SPs); PAH with small defects (SDs); and PAH after defect correction (CDs). METHODS AND RESULTS Data from consecutive PAH-CHD patients referred to our centre from 1 January 1998 to 31 May 2011 were collected. A contemporary group of idiopathic PAH patients was utilized for comparison. Treatment was per PAH guidelines, including combination therapy, with approved PAH-specific drugs. Survival was assessed with Kaplan-Meier analysis from the first invasive haemodynamic confirmation of PAH and compared across subgroups by log-rank test. Of 192 patients (mean age 41 ± 17 years; 61% female), 90 had ES (aged 41 ± 16 years); 48 SP (aged 47 ± 18 years); 10 SD (aged 25 ± 21 years); and 44 CD (aged 36 ± 17 years). Patients with ES had the highest baseline pulmonary vascular resistance and the lowest exercise capacity. Seventy-eight per cent were treated with approved PAH-specific drugs, and 44% were treated with combination therapy. Kaplan-Meier survival estimates (95% confidence interval) at 20 years for ES, SP, and CD were 87% (77-93%), 86% (60-96%), and 36% (12-72%, P = 0.0001 vs. ES; P = 0.004 vs. SP), respectively, and at 15 years for SD was 66% (16-91%, P = 0.015 vs. ES; P = 0.016 vs. SP). The survival of the 278 patients with idiopathic PAH appeared to be worse when compared with the PAH-CHD subgroups. CONCLUSION Relevant clinical, functional, haemodynamic, and survival differences were observed among subgroups. In particular, patients with CD and SD had the worst survival. These findings should be considered when planning medical or interventional treatment strategies in PAH-CHD patients.

Current Therapeutic Approaches to Pulmonary Arterial Hypertension

Pulmonary hypertension is a heterogeneous hemodynamic and pathophysiological state that is observed in a number of clinical conditions, which have been divided into six diagnostic groups. Although the increase in pulmonary pressure observed in these clinical groups may be similar, underlying disease mechanisms, diagnostic methods, and prognostic and therapeutic consequences are completely different. Pulmonary arterial hypertension is associated with several rare conditions that have comparable clinical and hemodynamic characteristics and exhibit virtually identical anatomical and pathological alterations in the lung microcirculation. These conditions include idiopathic and familial forms of the disease and disease forms associated with connective tissue disease, congenital heart defects involving systemic-to-pulmonary arterial shunts, portal hypertension, and HIV infection. It has been shown that treatment with specific drugs (e.g. prostanoids, endothelin-receptor antagonists and phosphodiesterase type-5 inhibitors) is effective in these patients and that these drugs can also be administered in various combinations. An evidence-based treatment algorithm has been developed for these patients. In patients with pulmonary hypertension due to left heart disease or lung disease, treatment focuses on the underlying condition and there is no convincing evidence that agents approved for pulmonary arterial hypertension are effective. For patients with chronic thromboembolic pulmonary hypertension, the treatment of choice is pulmonary endarterectomy. However, drugs intended specifically for the treatment of pulmonary arterial hypertension may be considered in inoperable cases or after suboptimal surgery.

Estrategias terapéuticas actuales en la hipertensión arterial pulmonar

La hipertension pulmonar es un estado hemodinamico y fisiopatologico heterogeneo que puede observarse en multiples situaciones clinicas, que se han clasificado en seis grupos diagnosticos. A pesar de que las elevaciones de la presion pulmonar pueden ser similares en los diferentes grupos clinicos, los mecanismos subyacentes, los enfoques diagnosticos y las repercusiones pronosticas y terapeuticas son completamente diferentes. La hipertension arterial pulmonar incluye trastornos infrecuentes que tienen en comun un cuadro clinico y hemodinamico comparable y unas alteraciones anatomopatologicas practicamente identicas en la microcirculacion pulmonar. Comprende formas idiopaticas y familiares, asi como las formas asociadas a enfermedades del tejido conjuntivo, cardiopatias congenitas con cortocircuito sistemico-pulmonar, hipertension portal e infeccion por el VIH. Se ha demostrado que determinados tratamientos farmacologicos especificos (prostanoides, antagonistas de los receptores de endotelina e inhibidores de la fosfodiesterasa tipo 5) son eficaces en este grupo y pueden administrarse tambien de manera combinada. Existe un algoritmo de tratamiento basado en la evidencia para estos pacientes. En los pacientes con hipertension pulmonar debida a una cardiopatia izquierda o enfermedades pulmonares, el tratamiento se centra en el trastorno subyacente, y no se ha demostrado de manera convincente que las medicaciones autorizadas para la hipertension arterial pulmonar sean eficaces. En los pacientes con hipertension pulmonar tromboembolica cronica, el tratamiento de eleccion es la endarterectomia pulmonar, y puede considerarse el uso de farmacos especificos para la hipertension arterial pulmonar en los casos inoperables o tras una intervencion quirurgica suboptima.