Marie-Caroline Certain1, Marie-Camille Chaumais2, Xavier Jaïs3, Laurent Savale3, Andrei Seferian4, Florence Parent4, Marjolaine Georges5, Nicolas Favrolt1, Arnaud Bourdin6, Clément Boissin7, Vincent Cottin8, Julie Traclet9, Sébastien Renard10, Violaine Noel11, François Picard12, Barbara Girerd3, Maria-Rosa Ghigna13, Frédéric Perros14, Olivier Sitbon3, Philippe Bonniaud5, Marc Humbert3, David Montani15. 1. Department of Respiratory and Intensive Care Medicine, National French Reference Constitutive Center for Rare Pulmonary Diseases, Hôpital François Mitterrand, Burgundy University Hospital, Dijon, France. 2. INSERM UMR_S 999 "Pulmonary Hypertension: Pathophysiology and Novel Therapies", Hôpital Marie Lannelongue, Le Plessis-Robinson, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Pharmacy, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; University of Paris-Saclay, Faculty of Pharmacy, Châtenay Malabry, France. 3. INSERM UMR_S 999 "Pulmonary Hypertension: Pathophysiology and Novel Therapies", Hôpital Marie Lannelongue, Le Plessis-Robinson, France; AP-HP, Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; University of Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France. 4. AP-HP, Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, Le Kremlin-Bicêtre, France. 5. Department of Respiratory and Intensive Care Medicine, National French Reference Constitutive Center for Rare Pulmonary Diseases, Hôpital François Mitterrand, Burgundy University Hospital, Dijon, France; University of Bourgogne Franche-Comté, School of Medicine, Dijon, France; INSERM UMR 123-1, LNC Faculty of Medicine and Pharmacy, Dijon, France. 6. Department of Respiratory Diseases, Hôpital Arnaud de Villeneuve, Montpellier University Hospitals, Montpellier, France; University of Montpellier, School of Medicine, Montpellier, France; INSERM U1046, Montpellier, France. 7. Department of Respiratory Diseases, Hôpital Arnaud de Villeneuve, Montpellier University Hospitals, Montpellier, France. 8. Department of Respiratory Medicine, National Coordinating Reference Center for Rare Pulmonary Diseases, Hôpital Louis Pradel, Lyon, France; Claude-Bernard Lyon 1 University, University of Lyon, INRA, UMR754, Lyon, France; UMR 754, Lyon, France. 9. Department of Respiratory Medicine, National Coordinating Reference Center for Rare Pulmonary Diseases, Hôpital Louis Pradel, Lyon, France. 10. Department of Cardiology, Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital de la Timone, Aix-Marseille University, Marseille, France. 11. Internal Medicine Department, Hôpital Robert-Debré, Reims, France. 12. Department of Cardiology, University Hospital of Bordeaux, Bordeaux, France. 13. Department of Pathology, Hôpital Marie Lannelongue, Le Plessis-Robinson, France. 14. INSERM UMR_S 999 "Pulmonary Hypertension: Pathophysiology and Novel Therapies", Hôpital Marie Lannelongue, Le Plessis-Robinson, France. 15. INSERM UMR_S 999 "Pulmonary Hypertension: Pathophysiology and Novel Therapies", Hôpital Marie Lannelongue, Le Plessis-Robinson, France; AP-HP, Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, Le Kremlin-Bicêtre, France; University of Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France. Electronic address: david.montani@aphp.fr.
Abstract
BACKGROUND: Pulmonary venoocclusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) predominantly characterized by pulmonary vein and capillary involvement. An association between chemotherapy, in particular mitomycin C (MMC), and PVOD has been reported. RESEARCH QUESTION: What are the characteristics of MMC-induced PVOD, and what is the prognosis for patients with MMC-induced PVOD? STUDY DESIGN AND METHODS: We report the clinical, functional, radiologic, and hemodynamic characteristics at diagnosis and outcomes of patients with PVOD from the French PH Registry after exposure to MMC. The results are expressed as the median (minimum-maximum). RESULTS: From June 2011 to December 2018, 17 incident cases of MMC-induced PVOD were identified. At diagnosis, these patients had severe clinical and functional impairment, with 12 patients having a New York Heart Association (NYHA) functional class of III or IV and a 6-min walk distance of 220 (0-465) m. Right heart catheterization confirmed severe precapillary PH with a mean pulmonary artery pressure of 38 (30-52) mm Hg, a cardiac index of 2.2 (1.5-4) L/(min × m2), and pulmonary vascular resistance of 8.3 (5.1-14.5) Wood units. The diffusing capacity of the lungs for carbon monoxide was markedly decreased at 31% (20%-51%) of the theoretical values associated with severe hypoxemia. MMC was withdrawn for all patients, and 14 patients received specific pulmonary arterial hypertension (PAH) therapies. Among these patients, mild but statistically insignificant improvements were observed in NYHA functional class (P = .10), 6-min walk distance (P = .09), and pulmonary vascular resistance (-4.7 Wood units; P = .052) at reassessment (median delay of 4.8 months). Three patients experienced pulmonary edema requiring the cessation or reduction of PAH treatment. The median overall survival was 20 months, and the 6-, 12-, and 24-month survival rates were 76%, 58%, and 18%, respectively. INTERPRETATION: PVOD after MMC treatment is a rare but life-threatening complication associated with a poor prognosis despite MMC withdrawal and PAH-specific therapy.
BACKGROUND: Pulmonary venoocclusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) predominantly characterized by pulmonary vein and capillary involvement. An association between chemotherapy, in particular mitomycin C (MMC), and PVOD has been reported. RESEARCH QUESTION: What are the characteristics of MMC-induced PVOD, and what is the prognosis for patients with MMC-induced PVOD? STUDY DESIGN AND METHODS: We report the clinical, functional, radiologic, and hemodynamic characteristics at diagnosis and outcomes of patients with PVOD from the French PH Registry after exposure to MMC. The results are expressed as the median (minimum-maximum). RESULTS: From June 2011 to December 2018, 17 incident cases of MMC-induced PVOD were identified. At diagnosis, these patients had severe clinical and functional impairment, with 12 patients having a New York Heart Association (NYHA) functional class of III or IV and a 6-min walk distance of 220 (0-465) m. Right heart catheterization confirmed severe precapillary PH with a mean pulmonary artery pressure of 38 (30-52) mm Hg, a cardiac index of 2.2 (1.5-4) L/(min × m2), and pulmonary vascular resistance of 8.3 (5.1-14.5) Wood units. The diffusing capacity of the lungs for carbon monoxide was markedly decreased at 31% (20%-51%) of the theoretical values associated with severe hypoxemia. MMC was withdrawn for all patients, and 14 patients received specific pulmonary arterial hypertension (PAH) therapies. Among these patients, mild but statistically insignificant improvements were observed in NYHA functional class (P = .10), 6-min walk distance (P = .09), and pulmonary vascular resistance (-4.7 Wood units; P = .052) at reassessment (median delay of 4.8 months). Three patients experienced pulmonary edema requiring the cessation or reduction of PAH treatment. The median overall survival was 20 months, and the 6-, 12-, and 24-month survival rates were 76%, 58%, and 18%, respectively. INTERPRETATION: PVOD after MMC treatment is a rare but life-threatening complication associated with a poor prognosis despite MMC withdrawal and PAH-specific therapy.
Authors: Bradley A Maron; Steven H Abman; C Greg Elliott; Robert P Frantz; Rachel K Hopper; Evelyn M Horn; Mark R Nicolls; Oksana A Shlobin; Sanjiv J Shah; Gabor Kovacs; Horst Olschewski; Erika B Rosenzweig Journal: Am J Respir Crit Care Med Date: 2021-06-15 Impact factor: 30.528