Martín-Garcia Ana, López-Fernández Teresa, Mitroi Cristina, Chaparro-Muñoz Marinela, Moliner Pedro, Martin-Garcia Agustin C, Martinez-Monzonis Amparo, Castro Antonio, Lopez-Sendon Jose L, Sanchez Pedro L
Department of Cardiology, Hospital Universitario de Salamanca-IBSAL, University of Salamanca, Paseo de San Vicente 58-187, 37007, Salamanca, Spain.
CIBERCV, Instituto de Salud Carlos III, Madrid, Spain.
ESC Heart Fail. 2020 Apr;7(2):763-767. doi: 10.1002/ehf2.12627. Epub 2020 Feb 5.
Current guidelines recommend sacubitril/valsartan for patients with heart failure and reduced left ventricular ejection fraction (LVEF), but there is lack of evidence of its efficacy and safety in cancer therapy-related cardiac dysfunction (CTRCD). Our aim was to analyse the potential benefit of sacubitril/valsartan in patients with CTRCD.
We performed a retrospective multicentre registry (HF-COH) in six Spanish hospitals with cardio-oncology clinics including all patients treated with sacubitril/valsartan. Demographic and clinical characteristics and laboratory and echocardiographic data were collected. Median follow-up was 4.6 [1; 11] months. Sixty-seven patients were included (median age was 63 ± 14 years; 64% were female, 87% had at least one cardiovascular risk factor). Median time from anti-cancer therapy to CTRD was 41 [10; 141] months. Breast cancer (45%) and lymphoma (39%) were the most frequent neoplasm, 31% had metastatic disease, and all patients were treated with combination antitumor therapy (70% with anthracyclines). Thirty-nine per cent of patients had received thoracic radiotherapy. Baseline median LVEF was 33 [27; 37], and 21% had atrial fibrillation. Eighty-five per cent were on beta-blocker therapy and 76% on mineralocorticoid receptor antagonists; 90% of the patients were symptomatic NYHA functional class ≥II. Maximal sacubitril/valsartan titration dose was achieved in 8% of patients (50 mg b.i.d.: 60%; 100 mg b.i.d.: 32%). Sacubitril/valsartan was discontinued in four patients (6%). Baseline N-terminal pro-B-type natriuretic peptide levels (1552 pg/mL [692; 3624] vs. 776 [339; 1458]), functional class (2.2 ± 0.6 vs. 1.6 ± 0.6), and LVEF (33% [27; 37] vs. 42 [35; 50]) improved at the end of follow-up (all P values ≤0.01). No significant statistical differences were found in creatinine (0.9 mg/dL [0.7; 1.1] vs. 0.9 [0.7; 1.1]; P = 0.055) or potassium serum levels (4.5 mg/dL [4.1; 4.8] vs. 4.5 [4.2; 4.8]; P = 0.5). Clinical, echocardiographic, and biochemical improvements were found regardless of the achieved sacubitril-valsartan dose (low or medium/high doses).
Our experience suggests that sacubitril/valsartan is well tolerated and improves echocardiographic functional and structural parameters, N-terminal pro-B-type natriuretic peptide levels, and symptomatic status in patients with CTRCD.
当前指南推荐沙库巴曲缬沙坦用于左心室射血分数(LVEF)降低的心力衰竭患者,但缺乏其在癌症治疗相关心脏功能障碍(CTRCD)中的疗效和安全性证据。我们的目的是分析沙库巴曲缬沙坦对CTRCD患者的潜在益处。
我们在西班牙六家设有心脏肿瘤门诊的医院进行了一项回顾性多中心注册研究(HF-COH),纳入所有接受沙库巴曲缬沙坦治疗的患者。收集人口统计学和临床特征以及实验室和超声心动图数据。中位随访时间为4.6[1;11]个月。纳入67例患者(中位年龄为63±14岁;64%为女性,87%至少有一项心血管危险因素)。从抗癌治疗到CTRD的中位时间为41[10;141]个月。乳腺癌(45%)和淋巴瘤(39%)是最常见的肿瘤,31%有转移性疾病,所有患者均接受联合抗肿瘤治疗(70%使用蒽环类药物)。39%的患者接受过胸部放疗。基线中位LVEF为33[27;37],21%有房颤。85%的患者接受β受体阻滞剂治疗,76%接受盐皮质激素受体拮抗剂治疗;90%的患者有症状,纽约心脏协会(NYHA)功能分级≥II级。8%的患者达到了沙库巴曲缬沙坦最大滴定剂量(50mg,每日两次:60%;100mg,每日两次:32%)。4例患者(6%)停用了沙库巴曲缬沙坦。随访结束时,基线N末端B型利钠肽前体水平(1552pg/mL[692;3624]对776[339;1458])、功能分级(2.2±0.6对1.6±0.6)和LVEF(33%[27;37]对42[35;50])均有改善(所有P值≤0.01)。肌酐(0.9mg/dL[0.7;1.1]对0.9[0.7;1.1];P = 0.055)或血钾水平(4.5mg/dL[4.1;4.8]对4.5[4.2;4.8];P = 0.5)未发现显著统计学差异。无论沙库巴曲缬沙坦剂量是低剂量还是中/高剂量,均发现临床、超声心动图和生化指标有改善。
我们的经验表明,沙库巴曲缬沙坦耐受性良好,可改善CTRCD患者的超声心动图功能和结构参数、N末端B型利钠肽前体水平及症状状态。