Our main findings are that (i) univariate and multivariate analyses yield very similar results and low variability of parameters yields more reliable multivariate sensitivity analyses, (ii) despite exacerbating Ca2+ impairment in HF, fibroblast to myocyte coupling does not alter the role of the main mechanisms regulating Ca2+ dynamics in myocytes, and (iii) drug action on ICaL and SERCA enhancement and NCX block would help CaT restoration in HF regardless of fibrosis presence. The gene discussed is CAT; the disease is fibrosis.