Natural History of Cardiac and Respiratory Involvement, Prognosis and Predictive Factors for Long-Term Survival in Adult Patients with Limb Girdle Muscular Dystrophies Type 2C and 2D.
Type 2C and 2D limb girdle muscular dystrophies (LGMD) are a group of autosomal recessive limb girdle muscular dystrophies manifested by proximal myopathy, impaired respiratory muscle function and cardiomyopathy. The correlation and the prognostic impact of respiratory and heart impairment are poorly described. We aimed to describe the long-term cardiac and respiratory follow-up of these patients and to determine predictive factors of cardio-respiratory events and mortality in LGMD 2C and 2D.



We reviewed the charts of 34 LGMD patients, followed from 2005 to 2015, to obtain echocardiographic, respiratory function and sleep recording data. We considered respiratory events (acute respiratory failure, pulmonary sepsis, atelectasis or pneumothorax), cardiac events (acute heart failure, significant cardiac arrhythmia or conduction block, ischemic stroke) and mortality as outcomes of interest for the present analysis.



A total of 21 patients had type 2C LGMD and 13 patients had type 2D. Median age was 30 years [IQR 24-38]. At baseline, median pulmonary vital capacity (VC) was 31% of predicted value [20-40]. Median maximal inspiratory pressure (MIP) was 31 cmH2O [IQR 20.25-39.75]. Median maximal expiratory pressure (MEP) was 30 cm H2O [20-36]. Median left ventricular ejection fraction (LVEF) was 55% [45-64] with 38% of patients with LVEF <50%. Over a median follow-up of 6 years, we observed 38% respiratory events, 14% cardiac events and 20% mortality. Among baseline characteristics, LVEF and left ventricular end diastolic diameter (LVEDD) were associated with mortality, whilst respiratory parameters (VC, MIP, MEP) and the need for home mechanical ventilation (HMV) were associated with respiratory events.



In our cohort of severely respiratory impaired type 2C and 2D LGMD, respiratory morbidity was high. Cardiac dysfunction was frequent in particular in LGMD 2C and had an impact on long-term mortality.



ClinicalTrials.gov NCT02501083.
Service de Réanimation médicale et unité de ventilation à domicile, centre de référence neuromusculaire GNHM, CHU Raymond Poincaré, APHP, Université de Versailles Saint Quentin en Yvelines, Garches, France.|Centre d'Investigation clinique et Innovation technologique CIC 14.29, INSERM, Garches, France.|Institut de Myologie, CHU Pitié Salpetrière, Centre de référence neuro musculaire Paris Est, Université Pierre et Marie Curie Paris VI, Paris, France.
Abdallah
A
Fayssoil
Service de Réanimation médicale et unité de ventilation à domicile, centre de référence neuromusculaire GNHM, CHU Raymond Poincaré, APHP, Université de Versailles Saint Quentin en Yvelines, Garches, France.|Centre d'Investigation clinique et Innovation technologique CIC 14.29, INSERM, Garches, France.
Adam
A
Ogna
SBIM, CHU Saint Louis, APHP, Université Paris Diderot, Paris, France.
Cendrine
C
Chaffaut
SBIM, CHU Saint Louis, APHP, Université Paris Diderot, Paris, France.
Sylvie
S
Chevret
Institut de Myologie, CHU Pitié Salpetrière, Centre de référence neuro musculaire Paris Est, Université Pierre et Marie Curie Paris VI, Paris, France.
Raquel
R
Guimarães-Costa
Laboratoire de biochimie et génétique moléculaire, hôpital Cochin, AP-HP, université Paris Descartes-Sorbonne Paris Cité, Paris, France.
France
F
Leturcq
Service de cardiologie, Hôpital Cochin, APHP, Université Paris Descartes-Sorbonne Paris Cité, Paris, France.
Karim
K
Wahbi
Service de Physiologie - Exploration fonctionnelles, CHU Raymond Poincaré, APHP, Université de Versailles saint Quentin en Yvelines, Garches, France.
Helene
H
Prigent
Service de Physiologie - Exploration fonctionnelles, CHU Raymond Poincaré, APHP, Université de Versailles saint Quentin en Yvelines, Garches, France.
Frederic
F
Lofaso
Service de Réanimation médicale et unité de ventilation à domicile, centre de référence neuromusculaire GNHM, CHU Raymond Poincaré, APHP, Université de Versailles Saint Quentin en Yvelines, Garches, France.
Olivier
O
Nardi
Service de Réanimation médicale et unité de ventilation à domicile, centre de référence neuromusculaire GNHM, CHU Raymond Poincaré, APHP, Université de Versailles Saint Quentin en Yvelines, Garches, France.
Bernard
B
Clair
Institut de Myologie, CHU Pitié Salpetrière, Centre de référence neuro musculaire Paris Est, Université Pierre et Marie Curie Paris VI, Paris, France.
Anthony
A
Behin
Institut de Myologie, CHU Pitié Salpetrière, Centre de référence neuro musculaire Paris Est, Université Pierre et Marie Curie Paris VI, Paris, France.
Tanya
T
Stojkovic
Institut de Myologie, CHU Pitié Salpetrière, Centre de référence neuro musculaire Paris Est, Université Pierre et Marie Curie Paris VI, Paris, France.
Pascal
P
Laforet
Service de Réanimation médicale et unité de ventilation à domicile, centre de référence neuromusculaire GNHM, CHU Raymond Poincaré, APHP, Université de Versailles Saint Quentin en Yvelines, Garches, France.|Centre d'Investigation clinique et Innovation technologique CIC 14.29, INSERM, Garches, France.
David
D
Orlikowski
Service de Réanimation médicale et unité de ventilation à domicile, centre de référence neuromusculaire GNHM, CHU Raymond Poincaré, APHP, Université de Versailles Saint Quentin en Yvelines, Garches, France.
Djillali
D
Annane
D000328:Adult; D001145:Arrhythmias, Cardiac / Q000473:pathology; D009202:Cardiomyopathies / Q000473:pathology*; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D008297:Male; D049288:Muscular Dystrophies, Limb-Girdle / Q000473:pathology*; D011379:Prognosis; D012131:Respiratory Insufficiency / Q000473:pathology*; D012132:Respiratory Muscles / Q000473:pathology*; D058088:Sarcoglycanopathies / Q000473:pathology*; D014797:Vital Capacity / Q000502:physiology