Establishment and preliminary assessment of a nomogram model for the risk of early complication of symptomatic heart failure in de novo patients with acute myeloid leukemia
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摘要: 目的 探讨初治急性髓系白血病早期并发症状性心力衰竭(心衰)的危险因素，建立预测症状性心衰风险的列线图模型。方法 回顾性分析苏州大学附属第一医院血液科2017年9月—2021年10月初治急性髓系白血病288例，根据3个月内是否发生症状性心衰分为心衰组(59例)和非心衰组(229例)。比较两组临床资料，采用多因素logistic回归分析筛选患者并发症状性心衰的危险因素；应用R语言建立预测症状性心衰风险的列线图模型，采用受试者工作曲线(ROC)分析列线图模型对初治急性髓系白血病早期并发症状性心力衰竭的预测效果。结果 心力衰竭组和非心力衰竭组患者的年龄、舒张压、丙氨酸氨基转移酶、乳酸脱氢酶、人血白蛋白、前白蛋白、3个月内地西他滨的使用率、降钙素原或G/GM试验阳性或败血症均差异有统计学意义(均P<0.05)。3个月后随访两组间体重变化及E峰、左心房大小变化均差异有统计学意义(均P<0.05)。多因素logistic回归分析结果显示，年龄(OR=1.026，95%CI：1.004~1.049，P=0.020)、舒张压(OR=0.958，95%CI：0.926~0.992，P=0.958)、前白蛋白(OR=0.995，95%CI：0.991~1.000，P=0.041)、感染指标或败血症(OR=2.590，95%CI：1.367~4.905，P=0.004)是初治急性髓系白血病并发症状性心衰的危险因素。列线图模型预测初治急性髓系白血病早期并发症状性心衰的一致性指数为0.714。ROC曲线分析显示，模型曲线下面积(AUC)为0.714(95%CI：0.645~0.783)，模型截断值为190.1分，灵敏度为0.831，特异度为0.359。结论 基于初治急性髓系白血病早期并发症状性心衰风险的列线图模型具有一定的区分度和预测效果，可辅助临床诊疗决策。Abstract: Objective To explore the risk factors of early complication of symptomatic heart failure in de novo patients with acute myeloid leukemia, and establish a nomogram model to predict the risk of symptomatic heart failure.Methods A total of 288 patients of de novo patients with acute myeloid leukemia in First Affiliated Hospital of Soochow University from September 2017 to October 2021 were retrospectively enrolled. Patients were divided into the heart failure group(n=59) and non-heart failure group(n=229) according the presence or absence of heart failure in three mouths. The risk factors of heart failure were analyzed by multivariate logistic regression analysis. R language was used to establish a nomogram model to predict the risk of early complication of symptomatic heart failure. Receiver operating characteristic(ROC) curve was used to explore the prediction efficiency of the nomogram model for symptomatic heart failure in de novo patients with acute myeloid leukemia.Results There were statistical significance differences in age, diastolic blood pressure, alanine aminotransferase, lactic dehydrogenase, albumin, prealbumin, decitabine usage, procalcitonin, G test/GM test or septicemia between the heart failure group and the non-heart failure group(all P<0.05). There were significant differences in body weight, E peak and left atrial size between the two groups after 3 months follow-up(all P<0.05). Multivariate logistic regression analysis showed that age(OR=1.026, 95%CI: 1.004-1.049, P=0.020), diastolic blood pressure(OR=0.958, 95%CI: 0.926-0.992, P=0.958), prealbumin(OR=0.995, 95%CI: 0.991-1.000, P=0.041) and G test/GM test or septicemia(OR=2.590, 95%CI: 1.367-4.905, P=0.004) were independent risk factors for symptomatic heart failure in de novo patients with acute myeloid leukemia. The consistency index of the nomogram model for predicting symptomatic heart failure in de novo patients with acute myeloid leukemia was 0.714. ROC curve showed that the area under the curve predicted by nomogram model was 0.714(95%CI: 0.645-0.783), the cutoff value was 190.1 points, and the sensitivity and specificity were 0.831 and 0.359, respectively.Conclusion Based on the risk factors for symptomatic heart failure in de novo patients with acute myeloid leukemia, a nomogram model for predicting the risk of heart failure is established, which has a certain differentiation degree and prediction effect, which is helpful to guide clinical diagnosis and treatment.
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Key words:
- heart failure /
- acute myeloid leukemia /
- nomogram model
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图 1 预测初治AML并发症状性心衰的列线图模型
Figure 1. The Nomogram model to predict symptomatic heart failure risk in de novo patients with AML
图 2 预测初治AML并发症状性心衰的列线图模型的Calibration曲线
Figure 2. The calibration curve of the Nomogram model to predict symptomatic heart failure risk in de novo patients with AML
图 3 Nomogram模型预测急性初治AML并发症状性心衰的ROC曲线
Figure 3. The ROC curves of the Nomogram model of symptomatic heart failure risk in de novo patients with AML
表 1 非心衰组和心衰组一般临床资料的比较
Table 1. Comparision of baseline data between the heart failure group and non-heart failure group
例(%), M(Q1, Q3), X±S 项目 非心衰组(229例) 心衰组(59例) t/χ2/Ζ P 男性 122(53.3) 24(40.7) 2.978 0.084 年龄/岁 39(28，51) 44(33，53) 1.986 0.047 BMI/(kg/cm2) 23.2±3.3 22.6±2.8 1.243 0.215 收缩压/mmHg 118.5±12.8 115.6±13.7 1.512 0.132 舒张压/mmHg 74.0±9.2 71.2±9.6 2.099 0.037 心率/(次/min) 88.0±13.3 88.1±13.9 -0.085 0.932 既往心血管病史及用药 高血压 27(11.8) 7(11.9) 0 0.987 糖尿病 9(3.9) 1(1.7) 0.191 0.622 心房颤动 1(0.4) 2(3.4) 0.108 瓣膜病 3(1.3) 0 1 血管硬化 3(1.3) 4(6.8) 3.836 0.05 β受体阻滞剂 2(0.9) 2(3.4) 0.187 ACEI/ARB 12(5.2) 2(3.4) 0.062 0.803 淋巴细胞/(×109/L) 1.39(0.64，3.03) 1.09(0.37，2.78) 1.424 0.155 红细胞比积 0.217(0.186，0.260) 0.206(0.182，0.240) 1.514 0.130 红细胞计数/(×1012/L) 2.29(1.91，2.74) 2.15(1.88，2.50) 1.567 0.117 白细胞计数/(×109/L) 3.34(1.20，9.70) 4.39(1.03，11.58) 0.365 0.715 血红蛋白/(g/L) 72(62，86) 67(62，77) 1.606 0.108 血小板计数/(×109/L) 30.0(21.0，48.5) 27.0(20.5，49.0) 0.331 0.74 肌酐/(μmol/L) 58.85(47.70，69.30) 59.00(47.90，72.30) 0.664 0.507 钾/(mmol/L) 3.96±0.38 3.99±0.41 -0.442 0.659 钠/(mmol/L) 139.40(137.30，141.50) 139.10(137.55，141.55) 0.036 0.971 ALT/(U/L) 21.7(13.6，33.5) 17.6(11.2，26.4) 2.086 0.037 AST/(U/L) 20.95(14.65，32.85) 19.90(13.30，29.20) 1.297 0.195 LDH/(U/L) 285.25(208.00，439.35) 432.00(218.30，642.90) 2.276 0.023 总蛋白/(g/L) 65.58±6.97 64.48±6.27 1.098 0.273 白蛋白/(g/L) 37.997±4.588 36.170±3.830 2.816 0.005 前白蛋白/(mg/L) 233.25(182.35，281.15) 195.30(160.40，233.90) 3.402 0.001 尿酸/(μmol/L) 201.25(141.35，282.10) 196(146.05，275.85) 0.071 0.943 肌酸激酶/(U/L) 31.50(23.00，46.25) 29.00(21.05，45.90) 0.614 0.539 心电图 PR间期/ms 140.5(130.0，152.0) 140.0(130.0，154.0) 0 1 QRS电轴/° 54(35，68) 52(25，60.5) 1.729 0.084 QRS时限/ms 85.50(79.00，92.00) 82.00(78.00，87.47) 1.951 0.051 QT间期/ms 366.0(350.0，382.0) 358.0(344.0，382.5) 1.006 0.315 QTc/ms 436.0(420.5，448.0) 436.0(422.5，450.0) 0.421 0.674 RV5/mV 1.630(1.361，1.985) 1.606(1.332，1.804) 0.997 0.319 SV1/mV 0.655(0.363，0.950) 0.654(0.420，0.965) 0.256 0.798 R+S/mV 2.294(1.904，2.753) 2.279(1.840，2.705) 0.505 0.614 骨髓穿刺及基因检查 幼稚细胞/% 58.1(31.7，80.1) 63.6(37.1，78.3) 0.812 0.417 CHIP 68(29.7) 17(27.1) 0.151 0.698 DNMT3A 37(16.2) 11(18.6) 0.209 0.648 TET2 18(7.9) 7(11.9) 0.949 0.33 ASXL1 17(7.4) 3(5.1) 0.118 0.732 JAK2 4(1.7) 0 0.585 TP53 6(2.6) 3(5.1) 0.303 0.582 SRSF2 4(1.7) 1(1.7) 0 1 SF3B1 1(0.4) 0 1 IDH1 13(5.7) 2(3.4) 0.124 0.707 IDH2 14(6.1) 5(8.5) 0.128 0.721 IDH1/IDH2 26(11.4) 7(11.9) 0.012 0.913 FLT3-ITD 49(21.4) 13(22.0) 0.011 0.916 心脏超声检查 主动脉根部内径/mm 32.0(29.0，34.0) 31.0(28.5，33.0) 1.568 0.117 室间隔厚度/mm 9(8，10) 9(8，9) 1.231 0.218 左室后壁厚度/mm 9(8，10) 9(8，9) 1.43 0.153 LVS/mm 49(46，52) 48(45，51) 0.232 0.816 LVD/mm 48.59±4.35 47.92±4.01 1.078 0.282 LA/mm 35.41±4.54 35.95±4.47 -0.822 0.412 LVEF/% 66.27±5.40 65.29±4.98 1.266 0.207 E峰/(cm/s) 86.52±19.22 90.89±19.26 -1.56 0.12 E/e’ 7.700(5.960，8.800) 7.800(6.425，9.345) 1.012 0.311 E/A 1.20(0.98，1.54) 1.29(1.00，1.50) 0.325 0.745 E/A<0.8 14(6.1) 1(1.7) 1.068 0.301 舒张功能异常 91(39.7) 24(40.7) 0.017 0.895 1 mmHg=0.133 kPa。ACEI/ARB：血管紧张素转化酶抑制剂/血管紧张素Ⅱ受体拮抗剂；AST：门冬氨酸氨基转移酶；LVS：左室收缩末期内径；LVD：左室舒张末期内径：LA：左房内径；LVEF；左室射血分数。 
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表 2 非心衰组和心衰组3个月内化疗用药和临床情况
Table 2. Comparison of drug use and clinical manifestation between the heart failure group and non-heart failure group
例(%), M(Q1, Q3) 项目 非心衰组(229例) 心衰组(59例) χ2/Ζ P 蒽环类药物累积剂量/(mg/m2) 72.00(49.85，108.00) 66.00(30.00，98.00) 1.299 0.194 高三尖杉酸 31(13.5) 6(10.2) 0.475 0.491 维奈克拉 21(9.2) 10(16.9) 2.955 0.086 依托泊苷 8(3.5) 2(3.4) 0 1 地西他滨 130(56.8) 46(78.0) 8.87 0.03 阿糖胞苷 222(96.9) 57(96.6) 0 1 阿扎胞苷 17(7.4) 5(8.5) 0 1 CR1 173(75.5) 46(78.0) 0.151 0.698 感染情况 PCT、G/GM(+) 52(22.7) 26(44.1) 10.839 0.001 肺部感染 77(33.6) 27(45.8) 2.996 0.083 皮肤感染 11(4.8) 4(6.8) 0.079 0.779 败血症 9(3.9) 6(10.2) 2.543 0.111 消化道感染 9(3.9) 2(3.4) 0 1 上呼吸道感染 17(7.4) 5(8.5) 0 1 粒细胞缺乏感染 25(10.9) 8(13.6) 0.323 0.57 感染指标或败血症 53(23.1) 26(44.1) 10.318 0.001
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表 3 非心衰组和心衰组3个月后心脏超声及体重变化
Table 3. Comparison of UCG and weight changes after 3 months between the heart failure group and non-heart failure group
M(Q1, Q3), X±S 指标 非心衰组(229例) 心衰组(59例) P t/Ζ ΔE/(cm/s) 15(-1，28) 21(8.5，33) 0.034 2.114 ΔLVS/mm 1(-2，3) 0(-2，2) 0.077 1.771 ΔLVD/mm -0.07±3.742 -0.51±3.36 0.418 0.811 ΔLA/mm -1(-3，2) -3(-5，0) 0.003 2.962 ΔLVEF/% -2.151±6.597 -1.186±6.972 0.323 -0.99 ΔE/e’ 0.230(-0.990，1.535) 0.850(-0.565，1.800) 0.190 1.311 ΔE/A 0.100(-0.120，0.340) 0.200(0.035，0.390) 0.063 1.856 体重减轻/kg 0.500(-2.000，3.500) 2.500(-0.900，4.475) 0.042 2.035
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表 4 初治AML并发症状性心衰风险的多因素logistic回归分析结果
Table 4. Logistic regression analysis of symptomatic heart failure risk in de novo patients with AML
因素 β SE Wald χ2 P OR 95%CI 年龄 0.026 0.011 5.426 0.020 1.026 1.004~1.049 舒张压 -0.043 0.018 5.959 0.015 0.958 0.926~0.992 前白蛋白 -0.005 0.002 4.184 0.041 0.995 0.991~1.000 感染指标或败血症 0.951 0.326 8.523 0.004 2.590 1.367~4.905 蒽环类药物累积剂量 -0.002 0.003 0.330 0.566 0.998 0.992~1.004
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