Marfan syndrome and related connective tissue disorders in the current era in Switzerland in 103 patients: medical and surgical management and impact of genetic testing.

INTRODUCTION: Marfan syndrome (MFS) and related connective tissue disorders (CTDs) are increasingly recognised. Genetic testing has greatly improved the diagnostic outcome/power over the last two decades. In this study we describe a multicentre cohort of adults with MFS and related CTDs, with a particular focus on results from genetic testing. METHODS: All patients with MFS and related CTDs were identified from the databases of five centres in the canton of Zurich. Echocardiographic and clinical findings including systemic Marfan score, use of medication and genetic results were retrospectively analysed. MFS was diagnosed using the revised Ghent criteria (including FBN1 genetic testing if available); other CTDs (Loeys-Dietz syndrome) were diagnosed by genetic testing only. RESULTS: A cohort of 103 patients were identified (62 index patients, 41 relatives of family members): 96 patients with MFS and 7 patients with other CTD, 54 males (52%), median age 23 years (range 1–75). The median systemic Marfan score was 5 (range 0–18). Only 40 patients (40/103, 39%) fulfilled criteria for systemic involvement (≥7 points). A history of aortic dissection was present in 14 out of 103 patients (14%). Echocardiographic data were available for all: aortic root enlargement (Z-score ≥2 in adults, Z-score ≥3 in children) was found in 49 patients (48%) and mitral valve prolapse in 64 (62%). Genetic testing had been performed in 80 patients (78%); FBN1 mutations were present in 69 patients (86%); other pathogenic mutations could be identified in seven patients (9%); no disease-causing mutation was found in four patients, three of them fulfilling the Ghent criteria of MFS. Of the mutation-positive patients, 33 had a systemic score of ≥7 and 43 had a systemic score of ≥5. Revised Ghent criteria were fulfilled in 70 patients: in 69 patients with FBN1 mutations and 1 patient with another CTD. Recommended treatment (beta-blocker, angiotensin receptor blocker) was taken by 63% of patients. CONCLUSIONS: In this cohort a high percentage of patients fulfilling the revised Ghent criteria for MFS underwent genetic testing, often leading to or confirming the diagnosis of MFS. Other CTDs could be discriminated best by genetic testing. With respect to the diagnosis of MFS and related CTDs, the usefulness of the systemic score is limited, showing the importance of genetic testing, which enabled definitive diagnosis in 95% of tested patients. Patient education on medical treatment still has to be improved. (Trial registration no: KEK-ZH-Nr. 2013-0241).

Treatment initiation in paediatric pulmonary hypertension: insights from a multinational registry.

Different treatment options for pulmonary hypertension have emerged in recent years, and evidence-based management strategies have improved quality of life and survival in adults. In children with pulmonary vascular disease, therapeutic algorithms are not so clearly defined; this study determined current treatment initiation in children with pulmonary hypertension in participating centres of a registry. Through the multinational Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension registry, patient demographics, diagnosis, and treatment as judged and executed by the local physician were collected. Inclusion criteria were >3 months and <18 years of age and diagnostic cardiac catheterisation consistent with pulmonary hypertension (mean pulmonary arterial pressure ⩾25 mmHg, pulmonary vascular resistance index ⩾3 Wood units×m2, and mean pulmonary capillary wedge pressure ⩽12 mmHg). At diagnostic catheterisation, 217/244 patients (88.9%) were treatment naïve for pulmonary hypertension-targeted therapy. Targeted therapy was initiated after catheterisation in 170 (78.3%) treatment-naïve patients. A total of 19 patients received supportive therapy, 28 patients were not started on therapy, and 26 patients (10.7%) were on targeted treatment before catheterisation. Among treatment-naïve subjects, treatment was initiated with one targeted drug (n=112, 51.6%), dual therapy (n=39, 18%) or triple-therapy (n=5, 2.3%), and calcium channel blockers with one targeted medication in one patient (0.5%). Phosphodiesterase inhibitors type 5 were used frequently; some patients with pulmonary hypertension related to lung disease received targeted therapy. There is a diverse therapeutic approach for children with pulmonary hypertension with a need of better-defined treatment algorithms based on paediatric consensus for different aetiologies including the best possible diagnostic workup.