Left ventricular SV was assessed by transthoracic echocardiography at baseline, and after 9 and 18 months of therapy. To determine the mechanisms underlying changes in LV SV, non-invasive pressure-volume parameters, including the end-systolic and end-diastolic pressure-volume relationship, were derived using single beat techniques. At baseline, the mean SV was 51 ± 14 ml. At 9 months, the least-squares mean change in SV was -0.3 ± 1.2 ml for patisiran and -5.4 ± 1.9 ml for placebo (p = 0.021). At 18 months, the least-squares mean change in SV was -1.7 ± 1.3 ml for patisiran and - 8.1 ± 2.3 ml for placebo (p = 0.016). Decline in LV SV was driven by diminished LV capacitance in placebo relative to patisiran.
Patisiran may delay progression of LV chamber dysfunction starting at 9 months of therapy. These data elucidate the mechanisms by which transthyretin-reducing therapies modulate progression of cardiac disease and need to be confirmed in ongoing phase 3 trials.
结果:基线时通过经胸超声心动图评估LVSV,以及9个月和18个月的治疗。为了确定LVSV变化的潜在机制,无创压力容积(PV)参数,包括收缩末期压力-容积关系和舒张末期压力-容积关系,是使用单拍技术得出的。在基线,平均SV为51±14mL。9个月时,对于patisiran和安慰剂,SV的LS平均变化为-0.3±1.2mL(p=0.021).18个月时,对于patisiran,SV的LS平均变化为-1.7±1.3mL,安慰剂为-8.1±2.3mL(p=0.016).LVSV的下降是由安慰剂中相对于patisiran的LV电容降低驱动的。
结论:Patisiran可能在治疗9个月时开始延迟左心室室功能障碍的进展。这些数据阐明了甲状腺素运载蛋白减少疗法调节心脏病进展的机制,需要在正在进行的III期试验中得到证实。