Hipertensión Pulmonar Secundaria a Enfermedad Tromboembólica ajlescano2004@yahoo.com.ar 42º Congreso Argentino de Medicina Respiratoria “Unidad Cardiorespiratoria. Simposio conjunto AAMR-SAC” Hipertensión Pulmonar Secundaria a Enfermedad Tromboembólica Coordinador de Cardiología. Sanatorio Finochietto. Bs As. Argentina Coordinador de Insuficiencia Cardíaca e Hipertensión Pulmonar. Hospital Santojanni Coordinador de Docencia. Sociedad Argentina de Cardiología Adrián J Lescano. MTSAC, MASEHF

PAPM > 25 mm Hg reposo Pulmonary arterial hypertension (PAH) Idiopathic PAH (IPAH) Heritable PAH Drug- and toxin-induced Associated PAH (APAH) Connective tissue diseases HIV infection Portal hypertension Congenital heart diseases Schistosomiasis Chronic hemolytic anemia HP Tromboembólica crónica PAPM > 25 mm Hg reposo

PAH y la CTEPH son 2 subgrupos de hipertension pulmonar. Se caracterizan por diferentes factores de riesgo. PAH: asociada a mutaciones genéticas BMPR2, HIV, enfermedades cardíacas congenital, tejido conectivo y exposición a drogas y toxinas. CTEPH: asociada a Ac antifosfolipidicos, esplenectomía, shunts ventriculo-atrial o marcapasos infectados. La terapéutica utilizada difiere entre la PAH y CTEPH. - Existen mecanismos combinados entre las 2 entidades, incluyendo la disfunción endotelial y el remodelado pulmonar distal. Humbert M. Eur Respir Rev 2010; 19: 115, 59–63

CLASIFICACION DE HP (NICE 2013) 1- Hipertensión arterial pulmonar 1.1- Idiopática 1.2- Hereditaria (BMPR / ALK1, Endoglin, SMAD9, CAV1, KCNK3 / Desconocido) 1.3- Inducidos por drogas y toxinas 1.4- Asociada con: Enfermedades del tejido conectivo, Hipertensión portal Infección por virus de inmunodeficiencia adquirida (HIV) Cardiopatías congénitas Esquistosomiasis, 1.5- Hipertensión pulmonar persistente del recién nacido 1´ - Enfermedad pulmonar veno-oclusiva y/o hemangiomatosis capilar pulmonar 2- Hipertensión pulmonar asociada a enfermedades cardíacas izquierda Disfunción sistólica / Disfunción diastólica / Enfermedad valvular Obstrucción congenita/adquirida del TSVI 3- Hipertensión pulmonar asociada a enfermedades respiratorias y/o hipoxemia 3.1- Enfermedad pulmonar obstructiva crónica 3.2- Enfermedad pulmonar intersticial 3.3- Otras afecciones mixtas restrictiva/obstructiva 3.4- Hipoventilación asociado a trastornos del sueño 3.5- Hipoventilación alveolar 3.6 Exposición crónica a grandes alturas 3.7 Anomalías del desarrollo 4- Hipertensión pulmonar tromboembólica crónica (CTEPH) 5- Hipertensión pulmonar con mecanismos multifactoriales no claros. Desordenes hematológicos: trastornos mieloproliferativos, esplenectomía, Anemia Hemolitica crónica Desordenes sistémicos: Sarcoidosis, histiocitosis, linfangiomatosis, neurofibromatosis, vasculitis. Desordenes metabólicos: enfermedad por depósito de glucógeno, enfermedad de Gaucher, desordenes tiroideos. Otros: Tumores obstructivos, mediastinitis fibrosante, insuficiencia renal crónica en diálisis Segmentación PH

CTEPH Epidemiologia Conclusiones Factores de Riesgo Tratamiento Diagnóstico Diferencial

CTEPH Epidemiologia Conclusiones Factores de Riesgo Tratamiento Diagnóstico Diferencial

Epidemiologia ¿Cuál es la relación? TEP Agudo CTEPH

Prevalencia de TEP en pacientes con CTEPH Epidemiologia La incidencia de CTEPH oscila entre 1% a 3.8%, a 2 años de seguimiento, en pacientes con tromboembolismo de pulmón agudo. Becattini C. Et al.Chest. 2006;130:172–175. 5. Pengo V. et al. N Engl J Med. 2004;350:2257–2264. Prevalencia de TEP en pacientes con CTEPH The pathophysiology of CTEPH remains unclear. The commonly accepted explanation (the embolic hypothesis) is that CTEPH is the result of single or recurrent PE arising from sites of venous thrombosis However, it has been suggested that CTEPH may also be caused by in situ thrombosis in the lung as a result of primary arteriopathy and endothelial dysfunction similar to that seen in PAH. This may help to explain why up to 30% of patients with CTEPH have no history of acute PE. *The study was a controlled retrospective cohort study that used logistic regression modelling. Three cohorts from four large European pulmonary vascular centres contributed prevalent cases: Austria, Slovak Republic, Germany, and Czech Republic. **This prospective registry was designed to include newly diagnosed (6 months) consecutive patients with CTEPH who did not receive PAH-targeted treatment before diagnosis from centers in Europe and Canada between February 2007 and January 2009. **Pepke-Zaba J and col. Circulation. 2011;124. *Bonderman Dand col. Eur Respir Rev 2009; 18.

Clase Funcional WHO Retrospectivo* Prospectivo** At the time of CTEPH diagnosis, a median of 14.1 months had passed since the first symptoms were observed Retrospectivo* Prospectivo** El diagnòstico se establece 14 meses posterior al comienzo de sìntomas **Pepke-Zaba J and col. Circulation. 2011;124. *Bonderman Dand col. Eur Respir Rev 2009; 18.

Diagnóstico Tardío Consulta CF III – IV 82,8 % CF III – IV 81,4 % Disnea 99% Edemas MI 40.5% Fatiga 31.5% Angina 15.3% Sincope 13.7% Consulta CF III – IV 82,8 % CF III – IV 81,4 % At diagnosis, the majority of patients were in NYHA functional class III or IV. Most common presenting symptoms were: dyspnea (99.1%), edema (40.5%), fatigue (31.5%), chest pain (15.3%), or syncope (13.7%). Retrospectivo* Prospectivo** **Pepke-Zaba J and col. Circulation. 2011;124. *Bonderman Dand col. Eur Respir Rev 2009; 18.

CTEPH Epidemiologia Conclusiones Factores de Riesgo Tratamiento Diagnóstico Diferencial

¿Quiénes son los pacientes en riesgo? Factores de Riesgo ¿Quiénes son los pacientes en riesgo? “Los factores de riesgo que predisponen al desarrollo de CTEPH incluyen el tamaño del trombo inicial y las condiciones médicas asociadas”. Kim NH and Lang IM. Eur Respir Rev 2012; 21: 123, 27–31

Factores de Riesgo Con el TEP, factores locales contribuyen a la genesis de trombosis in situ Proteínas procoagulantes y otros factores hemostáticos están asociados con incremento del riesgo de CTEPH. A number of procoagulant proteins and other haemostatic factors have been associated with an increased risk of CTEPH. Once a PE has occurred, these local factors may favour the formation of in situ thrombosis. - El incremento en los valores de factor VIII fue identificado como FR para CTEPH (45 con CTEPH vs 200 p con HP no tromboembolica (p 0.01) Wong CL, et al. Blood Coagul Fibrinolysis 2010; 21: 201–206. - Anomalías en la estructura y función del fibrinogeno en CTEPH. Morris TA, et al. Am J Respir Crit Care Med 2006; 173: 1270–1275. N.H. Kim and I.M. Lang. Eur Respir Rev 2012; 21: 123,27–31. G. Piazza and Goldhaber. N Engl J Med 2011;364:351-60.

Factores de Riesgo para CTEPH Sintomáticos Estudio prospectivo de 223 pacientes con TEP A prospective, long-term, follow-up study to assess the incidence of symptomatic CTPH in consecutive patients with an acute episode of pulmonary embolism but without prior venous thromboembolism. 223 patients were followed with acute pulmonary embolism. The following increased the risk of CTPH: a previous pulmonary embolism (odds ratio, 19.0), younger age (odds ratio, 1.79 per decade), a larger perfusion defect (odds ratio, 2.22 per decile decrement in perfusion), and idiopathic pulmonary embolism at presentation (odds ratio, 5.70). V. Pengo and coll. N Engl J Med 2004;350:2257-64

Los pacientes esplenectomizados desarrollan un estado protrombotico. Factores de Riesgo The association between splenectomy and CTEPH may be due to the presence of abnormal erythrocytes that would normally be filtered out of the blood by the spleen. The abnormal expression of phosphatidylserine on the surface of erythrocytes may trigger the coagulation process, resulting in the formation of thromboembolic material. Los mecanismos fisiopatológicos que asocian la esplenectomia y la CTEPH son escasamente definidos. Los pacientes esplenectomizados desarrollan un estado protrombotico. Jais X and col. Thorax 2005;60:1031–1034.

Ulceras Venosas Crónicas Factores de Riesgo FR en CTEPH OR (IC 95%) Valor de p Hipotiroidismo 6.10 (2.73-15.05) <0.001 Neoplasias 3.76 (1.47-10.43) 0.005 TVP Previa 4.52 (2.35-9.12) TVP Recurrente 14.49 (5.4-43) <0.0001 Ulceras Venosas Crónicas 2.84 (0.99-9) 0.053 APA/LAC 4.2 (1.56-12.2) 0.004 LES 0.11 (0-1.21) 0.076 Marcapaso Infectado 76.4 (7.6-10350) EII 3.19 (0.7-16.3) 0.12 Esplenectomía 17.8 (1.5-2438) 0.017 Hb Anormal 0.84 (0.05-122) 0.91 EPOC 0.47 (0.1-1.7) 0.25 Mielofibrosis 0.34 (0.02-8.4) 0.51 The study was a controlled retrospective cohort study. D. Bonderman, et al. Eur Respir Rev 2009; 18.

CTEPH Epidemiologia Conclusiones Factores de Riesgo Tratamiento Diagnóstico Diferencial

Diagnóstico de Hipertensión Pulmonar ESC/ERS GUIDELINES Diagnóstico de Hipertensión Pulmonar Differential diagnosis Diagnostic algorithm for PH. PAH should be considered in the differential diagnosis of exertional dyspnoea, syncope, angina, and/or progressive limitation of exercise capacity. The diagnostic process starts with the identification of the more common clinical groups of PH (group 2—left heart disease and group 3—lung diseases), then distinguishes group 4—CTEPH and finally makes the diagnosis and recognizes the different types in group 1—PAH. European Heart Journal 2009:30;2493–2537.

Diagnóstico de Hipertensión Pulmonar ESC/ERS GUIDELINES Diagnóstico de Hipertensión Pulmonar Differential diagnosis PAH should be considered in the differential diagnosis of exertional dyspnoea, syncope, angina, and/or progressive limitation of exercise capacity. The diagnostic process starts with the identification of the more common clinical groups of PH (group 2—left heart disease and group 3—lung diseases), then distinguishes group 4—CTEPH and finally makes the diagnosis and recognizes the different types in group 1—PAH. European Heart Journal 2009:30;2493–2537.

Diagnostico Diferencial Los consensos recomiendan la realización de un centellograma V/Q para detectar CTEPH Galie N, et al. ESC/ERS/ISHLT Guidelines. Eur Respir J 2009 Jaff MR, et al. Scientific Statement from the American Heart Association. Circulation 2011 Mehta S, et al. CTEPH: Clinical Practice Guideline. Can Respir J 2011 Wilkens H, et al. Cologne Consensus Conference. Int J Cardiol 2011 Centellograma V/Q: Sensibilidad 96-97% y especificidad 90-95% Tunariu N, et al. J Nucl Med 2007

Diagnóstico Diferencial Sospecha Confirmación Determinación del Riesgo Task Force 10: CTEPH Diagnostico e Intervención Sospecha - Ecocardiograma - VQ scan Confirmación - Cateterismo Derecho - Angiografía Pulmonar (Selective DSA, CTPA, MRA) Diagnostic algorithm for CTEPH, Nice 2013. - VQ scan is recommended for diagnosis and mandatory for exclusion of CTEPH. - Selective pulmonary angiography remains the gold standard for evaluation of operability. In centers with particular imaging experience in CTEPH. High quality CT or MR pulmonary angiography may be an acceptable alternative for disease confirmation. Determinación del Riesgo - Hemodinámica - Comorbidilidades - Cirugía/ CTEPH team con experiencia WSPH – Nice 2013.

CTEPH Epidemiologia Conclusiones Factores de Riesgo Tratamiento Diagnóstico Diferencial

PEA is la terapéutica de elecciòn en la CTEPH (1980), pero…… Tratamiento PEA TratamientoMédico Angioplastía Pulmonar PEA is la terapéutica de elecciòn en la CTEPH (1980), pero…… The current surgical procedure for PEA as a standard approach to the treatment of CTEPH was first developed in the late 1980s at the University of California at San Diego (California, USA) by the team led by Dr Ken Moser. Since the initial reports, there have been several modifications to the surgical approach to PEA. Approximately 4000 procedures have been completed in specialized centres in many countries worldwide. > 4000 intervenciones

Mortalidad Peri-operative/PVR Registro internacional de 679 pacientes Tratamiento Mortalidad Peri-operative/PVR Registro internacional de 679 pacientes p < 0.05 Surgical management and outcome of patients with chronic thromboembolic pulmonary hypertension: results from an international prospective registry. A total of 679 patients were registered from 1 Canadian and 26 European centers, of whom 386 (56.8%) underwent surgery. Mayer E, et al. J Thorac Cardiovasc Surg 2011;141:702-10.

“Seguridad de la PEA hoy” Tratamiento “Seguridad de la PEA hoy” La mortalidad hospitalaria es baja en centros con experencia: - PEACOG, 74 pacientes: 1.4% Vuylsteke et al Lancet 2011;378:1379 - UCSD, ultimos 5000 pacientes: 2.2% Madani et al. Ann Thor Surg 2012;94:97 - European prospective registry: 4.7% Mayer et al. Thorac Cardiovasc Res 2011;141:702

Tratamiento Clasificación THISTLETHWAITE classified CTEPH cases into 4 surgical categories based on endarterectomised specimens: type 1 and 2 lesions occur in the main lobar arteries and proximal segmental arteries, respectively, while type 3 lesions occur in more distal segmental arteries. An experienced surgeon can remove type 1–3 lesions with a high likelihood of haemodynamic improvement. However, type 4 lesions mostly result from distal vasculopathy with associated proximal intimal thickening, rather than intraluminal occlusion treatable with PEA [38], and represent conditions with a likely overlap with PAH. Therefore, patients in this group often have persistent post-operative PH caused by small-vessel Disease. Thistlethwaite et al. J Thorac Cardiovasc Surg 2002; 124: 1203–1211

Considerar tratamiento médico y/o dilatación con balón Clasificacion Type 1 Type 2 Type 3 Type 4 Enfermedad Proximal Enfermedad Distal Incierto / Inoperable (50%) PEA HP Residual (10%) Considerar tratamiento médico y/o dilatación con balón Thistlethwaite et al. J Thorac Cardiovasc Surg 2002; 124: 1203–1211

68 pacientes consecutivos con CTEPH inoperable Tratamiento PEA TratamientoMédico Angioplastia Pulmonar 68 pacientes consecutivos con CTEPH inoperable sometidos a angioplastía pulmonar con balón (APB). La APB fue realizada en diversas etapas y modalidades, para maximar la eficacia y reducir el riesgo de injuria por reperfusiòn. En total 4 sesiones por pacientes se realizaron, con un promedio de 3 vasos dilatados por sesion. Although balloon pulmonary angioplasty (BPA) for inoperable patients with chronic thromboembolic pulmonary hypertension was first reported over a decade ago, its clinical application has been restricted because of limited efficacy and complications. - Mizoguchi (Okayama Medical Center, Okayama, Japan): Sixty-eight consecutive patients with inoperable chronic thromboembolic pulmonary hypertension underwent BPA. They performed BPA in a staged fashion over multiple, separate procedures to maximize efficacy and reduce the risk of reperfusion pulmonary injury. A total of 4 (2–8) sessions were performed in each patient, and the number of vessels dilated per session was 3. Mizoguchi H., et al. Circ Cardiovasc Interv. 2012 Dec;5(6):748-55

Tratamiento TratamientoMédico PEA Angioplastía Pulmonar Although balloon pulmonary angioplasty (BPA) for inoperable patients with chronic thromboembolic pulmonary hypertension was first reported over a decade ago, its clinical application has been restricted because of limited efficacy and complications. - Mizoguchi (Okayama Medical Center, Okayama, Japan): Sixty-eight consecutive patients with inoperable chronic thromboembolic pulmonary hypertension underwent BPA. They performed BPA in a staged fashion over multiple, separate procedures to maximize efficacy and reduce the risk of reperfusion pulmonary injury. A total of 4 (2–8) sessions were performed in each patient, and the number of vessels dilated per session was 3. Mizoguchi H., et al. Circ Cardiovasc Interv. 2012 Dec;5(6):748-55

WHO FC MPAP C I PVR Tratamiento TratamientoMedico PEA Angioplastia Pulmonar WHO FC MPAP C I PVR Although balloon pulmonary angioplasty (BPA) for inoperable patients with chronic thromboembolic pulmonary hypertension was first reported over a decade ago, its clinical application has been restricted because of limited efficacy and complications. - Mizoguchi (Okayama Medical Center, Okayama, Japan): Sixty-eight consecutive patients with inoperable chronic thromboembolic pulmonary hypertension underwent BPA. They performed BPA in a staged fashion over multiple, separate procedures to maximize efficacy and reduce the risk of reperfusion pulmonary injury. A total of 4 (2–8) sessions were performed in each patient, and the number of vessels dilated per session was 3. Mizoguchi H., et al. Circ Cardiovasc Interv. 2012 Dec;5(6):748-55

Angioplastia Pulmonar Tratamiento PEA Tratamiento Médico Angioplastia Pulmonar PEA Angioplastia Pulmonar Experiencia > 7000 casos 127 casos reportados, 4 series de caso Mejoria Hemodinamica +++ + selección de casos inoperables Invasivo Alto Moderado Evento a largo plazo > 5 años de sobrevida 3 años Recomendaciones Aceptada, reproducible, guidelines Emergente, solo experimental, pendientes trials David Jenkins´s presentation. Task Force 10: WSPH 2013 – Nice

Tratamiento PEA Tratamiento Médico Angioplastia Pulmonar Tratamiento Médico: Arteriopatía de pequeños vasos similar a la HP idiopática e incremento de la concentración de ET-1. David Jenkins´s presentation. Task Force 10: WSPH 2013 – Nice

Enfermedad de pequeños vasos que contribuyen a la CTEPH: Tratamiento Enfermedad de pequeños vasos que contribuyen a la CTEPH: 1- Obstrucción de arterias sub-segmentarios y distales que exceden al alcanze de la PEA. 2- Arteriopatia pulmonar de pequeñas arterias musculares y arteriolas distales. 3- La histopatologia del tejido pulmonar demuestra engrosamiento intimal y lesiones plexiformes en arterias pequeñas y arteriolas. Persistent PH from small-vessel disease following PEA remains the major cause of post-operative morbidity and mortality in CTEPH. La HP persistente de pequeños vasos, es la mayor causa de morbi-mortalidad post-operatoria N.H. Kim and I.M. Lang. Eur Respir Rev 2012; 21: 123,27–31. G. Piazza and Goldhaber. N Engl J Med 2011;364:351-60.

Tratamiento “Terapéutica Medica en CTEPH” ¿Evidencia? 2010 2008 2007 Open-label uncontrolled study Ghofrani HA, et al. Eur Respir J. 2010;36(4):792-90 Non-randomized, open-label prospective study 2008 Suntharalingam J, et al. Chest. 2008;134(2):229-36 Jaïs X, et al. J Am Coll Cardiol. 2008;52(25):2127-34. open-label uncontrolled clinical trial Seyfarth HJ, et al. Respiration. 2007;74(3):287-92.   2007 Reichenberger F., et al. Eur Respir J. 2007(5):922-7. Retrospective analysis Open-label uncontrolled study Skoro-Sajer N., et al. J Thromb Haemost. 2007(3):483-9. Cabrol S., et al. J Heart Lung Transplant. 2007(4):357-62. Caso series Bonderman D, et al. Chest. 2005;128(4):2599-603. 2005 Open-label multicenter study Hoeper MM, et al. Chest. 2005;128(4):2363-7. 2003 Ghofrani HA., et al. Am J Respir Crit Care Med. 2003;167(8):1139-41. Open-label uncontrolled study 2002 H. OlschewskI, et al. N Engl J Med 2002;347:322-9.

Tratamiento “Terapéutica Medica en CTEPH” ¿Evidencia? 2008 2002 Estudio piloto con escaso poder sobre el end point primario. “Terapéutica Medica en CTEPH” ¿Evidencia? CHEST. Riociguat 2008 Suntharalingam J, et al. Chest. 2008;134(2):229-36 Jaïs X, et al. J Am Coll Cardiol. 2008;52(25):2127-34. El BENEFiT fue un doble-ciego, randomizado, placebo-controlado en CTEPH CTEPH; 32,7% de los pacientes. 2002 H. OlschewskI, et al. N Engl J Med 2002;347:322-9.

Características demográficas y basales Tratamiento BENEFiT Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension. A Randomized, Placebo-Controlled Trial Características demográficas y basales Placebo (n 80) Bosentan (n 77) Age, mean ± SD(ys) 63.1 ± 10.3 63.0 ± 12.9 Females (%) 58.8 71.4 Previous PEA (%) 27.5 28.6 PVR, mean ± SD(dyn.s.cm-5) 787 333 778 323 6MWD, mean ± SD(m) 344.5 82.6 340.0 85.3 WHO functional class (II/III/IV) 22/56/2 22/51/3 Cardiac index, mean±SD(l/min/m2) 2.35 0.55 2.24 0.54 TPR, mean SD (dyn·s·cm-5) 936 347 944 340 mPAP, mean SD (mm Hg) 47.4 12.5 44.2 10.4 mRAP, mean SD (mm Hg) 8.4 6.0 8.3 6.1 Borg dyspnea index, mean SD 4.1 2.3 4.4 2.0 NT-proBNP, mean SD (ng/l) 1,405 ±1,882 1,481 ±1,833 The BENEFiT study was a double-blind, randomized, placebo-controlled study in CTEPH including patients with either inoperable CTEPH or persistent/recurrent pulmonary hypertension after PEA (>6 months after PEA). 157 patients were enrolled and randomized: 80 to placebo, 77 to bosentan. Jaïs X, et al. J Am Coll Cardiol. 2008;52(25):2127-34.

Tratamiento Resultados hemodinámicos RVP: Reducción significativa Indice Cardíaco: Incremento significativo A statistically significant treatment effect (TE) of bosentan over placebo on PVR was demonstrated: 24.1% of baseline (95% confidence interval [CI]: 31.5% to 16.0%; p 0.0001). Total pulmonary resistance (TE: 193 dyn·s·cm5;95% CI: 283 to 104 dyn·s·cm5; p 0.0001) and cardiac index (TE: 0.3 l·min1·m2; 95% CI: 0.14 to 0.46 l·min1·m2; p 0.0007) improved. Mean TE on 6-min walk distance was 2.2 m (95% CI: 22.5 to 26.8 m;p 0.5449). Bosentan treatment was well tolerated. Jaïs X, et al. J Am Coll Cardiol. 2008;52(25):2127-34.

Tratamiento Resultados clínicos Significativos efectos en la reducción de síntomas (Borg dyspnea index*) CF WHO* A statistically significant treatment effect (TE) of bosentan over placebo on PVR was demonstrated: 24.1% of baseline (95% confidence interval [CI]: 31.5% to 16.0%; p 0.0001). Total pulmonary resistance (TE: 193 dyn·s·cm5;95% CI: 283 to 104 dyn·s·cm5; p 0.0001) and cardiac index (TE: 0.3 l·min1·m2; 95% CI: 0.14 to 0.46 l·min1·m2; p 0.0007) improved. Mean TE on 6-min walk distance was 2.2 m (95% CI: 22.5 to 26.8 m;p 0.5449). Bosentan treatment was well tolerated. Jaïs X, et al. J Am Coll Cardiol. 2008;52(25):2127-34.

Reducción significativa del NT-pro-BNP* Tratamiento Reducción significativa del NT-pro-BNP* Efectos en el 6MWD A statistically significant treatment effect (TE) of bosentan over placebo on PVR was demonstrated: 24.1% of baseline (95% confidence interval [CI]: 31.5% to 16.0%; p 0.0001). Total pulmonary resistance (TE: 193 dyn·s·cm5;95% CI: 283 to 104 dyn·s·cm5; p 0.0001) and cardiac index (TE: 0.3 l·min1·m2; 95% CI: 0.14 to 0.46 l·min1·m2; p 0.0007) improved. Mean TE on 6-min walk distance was 2.2 m (95% CI: 22.5 to 26.8 m;p 0.5449). Bosentan treatment was well tolerated. Jaïs X, et al. J Am Coll Cardiol. 2008;52(25):2127-34.

Diagnóstico de CTEPH No-operable Operable Algoritmo Terapéutico Diagnóstico de CTEPH Anticoagulación Determinar la Operabilidad por el team CTEPH No-operable Operable 2° Opinión de centros con experiencia PEA Tratamiento médico Terapias Emergentes Hipertensión Pulmonar persistente Referir a un centro de trasplante pulmonar M. Delcroix. WSPH (Task Force 10) – Nice 2013

CTEPH Conclusiones Epidemiologia 1% to 3.8% de los pacientes desarrollan CTEPH dentro de los 2 años de TEP agudo. 80% diagnóstico en CF III-IV Factores de Riesgo Tamaño del trombo inicial y condiciones medicas. Diagnostico Diferencial PAH: V/Q scan normal → aleja la sospecha CTEPH. La principal decision es identificar pacientes con accesibilidad para la tromboendarterectomia, donde el objetivo es la reducción sustancial en la resistencia vascular pulmonar. Tratamiento medico debe reservarse para cuadros inoperables o aquellos con HP persistente o recurrente. Tratamiento