OBJECTIVES: To validate the Kansas City Cardiomyopathy Questionnaire (KCCQ) in a rare cardiac disease clinical trial. Given the scarcity of the patients, the qualitative and quantitative validations were performed simultaneously. METHODS: Twelve patients completed the KCCQ and were interviewed to assess their comprehension of the questionnaire and its relevance. Item distribution and missing data were analysed. RESULTS: The qualitative analysis showed that the KCCQ covered all domains patients deemed important, except avoidance behavior who they reported lacking. Patients found the recall period (“over the past two weeks”) too short, not always adapted to the study context. The quantitative analysis showed that the KCCQ was well accepted, with good reliability, construct and distributional properties. Several items showed a ceiling effect, that qualitative analysis enabled to interpret. First, around 70% of patients answered that they had never had swelling in the morning (item 3). For patients this symptom was being an issue mostly in the evening. Second, over 60% of patients answered that they had not been bothered by swelling (item 4). The term “bothered” was not understood by some patients. Third, over 70% of patients answered that shortness of breath never limited their ability and/or limited their ability less than once week to do what they wanted (item 7). Only two patients reported changing their lifestyle to avoid shortness of breath. Last, over 80% of patients answered that they had never been forced to sleep sitting up because of shortness of breath (item 9). No patient reported having been affected by this symptom. CONCLUSIONS: The KCCQ has good content validity, qualitatively and quantitatively. However some limitations in our context of use were identified during the quantitative analysis and explained by the qualitative analysis. By using a convergent design we improved the use and interpretation of the KCCQ in a future planned clinical trial.