Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
Molecular and Cellular Cardiology Lab, IRCCS 'L. Spallanzani', Rome, Italy.
Eur Heart J. 2022 Sep 21;43(36):3463-3473. doi: 10.1093/eurheartj/ehac348.
Long-term results of the Tailored IMmunosuppression in virus-negative Inflammatory Cardiomyopathy (TIMIC) trial protocol have been evaluated.
Eighty-five patients with endomyocardial biopsy-proven virus-negative chronic inflammatory cardiomyopathy were enrolled in the randomized, double-blind, placebo-controlled TIMIC trial and received prednisone and azathioprine (n = 43) vs. placebo (n = 42) for 6 months. Immunosuppressive treatment promoted an improvement in cardiac function in 88% of the cases compared with none of the patients in the placebo group, which were switched to a 6-month immunosuppressive therapy at the end of the 6-month study period. Long-term (up to 20 years) clinical outcomes of the whole cohort of 85 patients originally enrolled in the TIMIC trial (Group A) were compared with those of a 1:2 propensity score-matched control cohort of patients untreated with the TIMIC protocol (Group B) and followed for a comparable period of time. The primary outcome was a composite of cardiovascular death and heart transplantation. At long-term follow-up, the risk of cardiovascular death [hazard ratio (HR) 6.77; 95% confidence interval (CI) 2.36-19.45] and heart transplantation (HR 7.92; 95% CI 1.80-34.88) was significantly higher in Group B patients. Group A showed a persistent improvement in the left ventricular ejection fraction compared with Group B (HR 7.24; 95% CI 3.05-17.18). A higher number of Group B patients underwent implantable cardioverter defibrillator implantation. The incidence of recurrent myocarditis was similar between groups, and patients with evidence of a recurrent cardiac inflammatory process promptly responded to a TIMIC protocol application.
Virus-negative inflammatory cardiomyopathy benefits from immunosuppressive therapy even after long-term follow-up. Recurrence appears to respond to a new TIMIC protocol application.
评估 Tailored IMmunosuppression in virus-negative Inflammatory Cardiomyopathy（TIMIC）试验方案的长期结果。
85 例经心内膜心肌活检证实为病毒阴性慢性炎症性心肌病的患者被纳入随机、双盲、安慰剂对照的 TIMIC 试验，并接受泼尼松和硫唑嘌呤（n=43）与安慰剂（n=42）治疗 6 个月。与安慰剂组无一例患者相比，免疫抑制治疗使 88%的病例心功能得到改善，这些患者在 6 个月研究结束时被转换为 6 个月的免疫抑制治疗。对最初纳入 TIMIC 试验的 85 例患者的整个队列（A 组）的长期（最长 20 年）临床结果与未接受 TIMIC 方案治疗的患者的 1:2 倾向评分匹配对照组（B 组）进行比较，并随访了相当长的一段时间。主要终点是心血管死亡和心脏移植的复合终点。长期随访时，B 组患者心血管死亡（风险比 [HR] 6.77；95%置信区间 [CI] 2.36-19.45）和心脏移植（HR 7.92；95%CI 1.80-34.88）的风险显著更高。A 组与 B 组相比，左心室射血分数持续改善（HR 7.24；95%CI 3.05-17.18）。B 组更多患者接受了植入式心脏复律除颤器植入。两组间复发性心肌炎的发生率相似，且有心脏炎症复发证据的患者及时应用 TIMIC 方案治疗后迅速起效。
即使在长期随访后，病毒阴性炎症性心肌病也能从免疫抑制治疗中获益。复发似乎对新的 TIMIC 方案应用有反应。
