The effect of tafamidis treatment on cardiovascular aging in patients with Transthyretin cardiomyopathy. An observational study

Abstract

Abstract Background Sporadic cardiac transthyretin amyloidosis (wtATTR) is a degenerative age-related disease with dismal prognosis and continuously increasing incidence. ATTR may have adverse effects also on vascular function and accelerate vascular aging. Tafamidis, a new agent that stabilizes the TTR tetramer improves wtATTR prognosis; however, whether tafamidis exerts any effect on vascular aging processes is unknown. Purpose To evaluate the effect of tafamidis treatment on markers of vascular aging. Methods This is an observational, non-interventional longitudinal study. wtATTR patients receiving tafamidis were evaluated prospectively at baseline, 3 months, 6 months and 1 year for non-invasive markers of vascular aging including arterial stiffness by pulse wave velocity (PWV, primary outcome measure), and markers derived from pulse wave analysis and compared to non-amyloidosis elderly controls (N=30, age>70 years) who were re-assessed for vascular function 1 year after their baseline visit. Results Twenty-one patients with wtATTR and were receiving tafamidis completed all 4 visits. Linear mixed model analysis revealed that PWV progressively decreased compared to baseline, during follow-up visits in patients receiving tafamidis [baseline vs a) 3 months: -0.95 mean difference (95%CI -1.73, -0.159) p-value=0.0121, b) 6 months: -1.36 mean difference (95%CI -2.19, -0.54) p-value=0.0002, c) 1 year: -1.08 mean difference (95%CI -2.03, -0.12) p-value=0.002]. The non-amyloidosis elderly control group presented a significant increase in PWV after 1 year compared to baseline (13.63 m/s vs 11.99 m/s, p =0.001 respectively, Wilcoxon rank test), while PWV was significantly lower in wtATTR group after 1 year compared to the control group despite younger mean age of the latter (p for interaction=0.0089). Central systolic blood pressure was decreased after 6 months of treatment, while it returned to baseline levels after 1 year [mixed model analysis, baseline vs 6 months -5.95 mean difference (95%CI -10.31, -1.60) p-value=0.007, baseline vs 1 year -0.47 mean difference (95%CI -5.42, 4.49) p-value=0.854]. A similar trend was observed for central diastolic blood pressure, although not achieving statistical significance (mixed model analysis, baseline vs 6 months -2.66 mean difference (95%CI -5.72, 0.40) p-value=0.088, baseline vs 1 year 0.005 mean difference (95%CI -3.47, 3.48) p-value=0.998]. Conclusion The results of this prospective study suggest that tafamidis may delay vascular aging in addition to cardiac aging in patients with wtATTR.