左心室射血分数保留性心力衰竭患者预后相关生物靶向标志物的表达特征

目的分析射血分数下降的心力衰竭(heart failure with reduced ejection fraction,HFrEF)和射血分数保留(或正常)的心力衰竭(heart failure with preserved ejection fraction,HFpEF)患者生物靶向标志物表达差异情况。评估生物靶向标志物对HFpEF识别与预后判断价值。方法连续选择2015年1月至2016年5月香港大学深圳医院100例HFpEF(左心室射血分数≥50%)及310例HFrEF(左心室射血分数<50%)患者,收集患者基本临床治疗与相关生物靶向标志物,以12个月不良事件为研究终点。结果HFpEF患者中,氨基末端脑钠肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)浓度[1911(877~4130)pg/mL vs.3001(1498~6120)pg/mL,P<0.05]、高敏肌钙蛋白T(high-sensitivity troponin T,hsTnT)浓度[21.1(15.9~41)pg/mL vs.31.2(18.1~52.7)pg/mL,P<0.05]、高敏C-反应蛋白(high-sensitivity C-reactive protein,hs-CRP)浓度[3.6(1.7~6.9)mg/L vs.2.1(0.9~4.8)mg/L,P<0.05]明显低于HFrEF患者,而胱抑素C浓度高于HFrEF患者[1.7(1.3~2.2)mg/L vs.1.4(1.0~2.0)mg/L,P<0.05],差异有统计学意义。而且在HFpEF组中白细胞介素-6,hsTnT和尿素氮与终点事件有关,NT-proBNP对HFpEF患者远期预后无统计学意义。结论生物标志物在HFpEF与HFrEF患者中存在差异性表达情况。在HFpEF患者中,预后相关的预测因子可能进一步提高临床对于HFpEF诊断、风险评估与治疗。     

心力衰竭加重并左室射血分数降低患者的QRS时限与预后

目的观察住院期间QRs时限对心力衰竭并左室射血分数降低预后的影响。方法回顾性分析心力衰竭并左室射血分数降低（≤40％）或正常的住院患者住院期间的QRs波群时限。结果3002例患者纳入研究,其中正常QRS波群时限1745例（〈120ms）,QRS波群延长（≥120ms）1257例。平均随访10个月,基础QRS波群时限正常患者全因死亡率为18．8％,基础QRS波群延长患者为28．3％（nR。1．62,95％CIL38～1．88）。基础QRS波群正常患者心血管死亡和心力衰竭住院率为31．5％和35．8％,延长者则为39．0％和43．6％（朋=1．40、1．42;95％CIL25-1．60、1．18-1．72）。QRS波群时限延长与增加全因死亡率危险性相关（HR=1．25：95％C11．03～1．52）,并增加心血管死亡或心力衰竭住院率（HR=1．21、1．28,95％CIL10～1．40、1．12～1．38）。基础Qas波群延长患者最后住院心电图QRS波群正常者仅为4．0％。结论延长的QRS波群在LVEF降低患者中十分多见,是出院后高患病率和高死亡率的独立预测因素。     

Effect of vericiguat on left ventricular structure and function in patients with heart failure with reduced ejection fraction: The VICTORIA echocardiographic substudy

Aim

Vericiguat significantly reduced the primary composite outcome of heart failure (HF) hospitalization or cardiovascular death in the VICTORIA trial. It is unknown if these outcome benefits are related to reverse left ventricular (LV) remodelling with vericiguat in patients with HF with reduced ejection fraction (HFrEF). The aim of this study was to compare the effects of vericiguat versus placebo on LV structure and function after 8 months of therapy in patients with HFrEF.

Methods and results

Standardized transthoracic echocardiography (TTE) was performed at baseline and after 8 months of therapy in a subset of HFrEF patients in VICTORIA. The co-primary endpoints were changes in LV end-systolic volume index (LVESVI) and LV ejection fraction (LVEF). Quality assurance and central reading were performed by an echocardiographic core laboratory blinded to treatment assignment. A total of 419 patients (208 vericiguat, 211 placebo) with high-quality paired TTE at baseline and 8 months were included. Baseline clinical characteristics were well balanced between treatment groups and echocardiographic characteristics were representative of patients with HFrEF. LVESVI significantly declined (60.7 ± 26.8 to 56.8 ± 30.4 ml/m²; p < 0.01) and LVEF significantly increased (33.0 ± 9.4% to 36.1 ± 10.2%; p < 0.01) in the vericiguat group, but similarly in the placebo group (absolute changes for vericiguat vs. placebo: LVESVI −3.8 ± 15.4 vs. −7.1 ± 20.5 ml/m²; p = 0.07 and LVEF +3.2 ± 8.0% vs. +2.4 ± 7.6%; p = 0.31). The absolute rate per 100 patient-years of the primary composite endpoint at 8 months tended to be lower in the vericiguat group (19.8) than the placebo group (29.6) (p = 0.07).

Conclusions

In this pre-specified echocardiographic study, significant improvements in LV structure and function occurred over 8 months in both vericiguat and placebo in a high-risk HFrEF population with recent worsening HF. Further studies are warranted to define the mechanisms of vericiguat's benefit in HFrEF.     

Evolocumab has no effects on heart failure with reduced ejection fraction injury biomarkers: The EVO-HF trial

Aim

Patients with heart failure with reduced ejection fraction (HFrEF) have not been shown to benefit from statins. We hypothesized that, by limiting disease progression in stable HFrEF of ischaemic etiology, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab could reduce circulating troponin levels, a surrogate biomarker of myocyte injury and atherosclerosis progression.

Methods and results

The EVO-HF multicentre prospective randomized trial compared evolocumab (420 mg/month administered subcutaneously) plus guideline-directed medical therapy (GDMT; n = 17) versus GDMT alone (n = 22) for 1 year in patients with stable coronary artery disease and left ventricular ejection fraction (LVEF) <40%, ischaemic aetiology, New York Heart Association class II, N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥400 pg/ml, high-sensitivity troponin T (hs-TnT) >10 pg/ml, low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dl. The primary endpoint was change in hs-TnT concentration. Secondary endpoints included NT-proBNP, interleukin-1 receptor-like 1 (ST2), high-sensitivity C-reactive protein (hs-CRP), LDL, low-density lipoprotein receptor (LDLR), high-density lipoprotein cholesterol (HDL-C), and PCSK9 levels at 1 year. Patients were mainly Caucasian (71.8%), male (79.5%), relatively young (mean age 68.1 ± 9.4 years), with a mean LVEF of 30.4 ± 6.5%, and managed with contemporary treatments. No significant changes in hs-TnT levels were observed in any group at 1 year. NT-proBNP and ST2 levels decreased in the GDMT plus evolocumab group (p = 0.045 and p = 0.008, respectively), without changes in hs-CRP, HDL-C, or LDLR. Total and LDL-C decreased in both groups, significantly higher in the intervention group (p = 0.003), and PCSK9 levels increased in the intervention group.

Conclusions

This prospective randomized pilot trial, although with the limitation of the small sample size, does not support the benefit of evolocumab in reducing troponin levels in patients with elevated LDL-C levels, history of coronary artery disease, and stable HFrEF.     

峰值氧耗量对非射血分数减低的心力衰竭患者预后评估的价值

目的:探讨心肺运动试验重要参数对非射血分数减低心力衰竭(HFr EF)预后评价的价值。方法:前瞻性入组2014年1月到2018年6月,我院诊断为非HFr EF患者,记录患者再入院及死亡事件,最后进行生存分析。结果:入选124例患者,平均随访(24±5)个月,10例患者死亡,32例患者因心力衰竭再住院治疗。心力衰竭组患者峰值氧耗量劣于正常健康对照组[(17.4±2.7)vs.(31.5±3.2)m L·kg^-1·min^-1,P<0.05]。事件组峰值氧耗量低于无事件组[(13.9±2.1)vs.(19.2±3.5)m L·kg^-1·min^-1,P<0.05]。多因素分析表明:峰值氧耗量是预测非HFr EF患者预后的指标(HR=0.81,95%CI:0.76~0.92,P<0.002)。结论:峰值氧耗量可以很好预测非HFr EF患者预后。     

A flattening oxygen consumption trajectory phenotypes disease severity and poor prognosis in patients with heart failure with reduced,mid‐range,and preserved ejection fraction

Background

In heart failure (HF), a flattening oxygen consumption (VO₂) trajectory during cardiopulmonary exercise test (CPET) reflects an acutely compromised cardiac output. We hypothesized that a flattening VO₂ trajectory is helpful in phenotyping disease severity and prognosis in HF with either reduced (HFrEF), mid‐range (HFmrEF), or preserved (HFpEF) ejection fraction.

Methods and results

Overall, 319 HF patients (198 HFrEF, 80 HFmrEF, and 41 HFpEF) underwent CPET. A flattening VO₂ trajectory was tracked and defined as an inflection of VO₂ linearity as a function of work rate with a second slope downward inflection >35% extent of the first one. Peak VO₂, the minute ventilation/carbon dioxide production (VE/VCO₂) slope, and the presence of exercise oscillatory ventilation (EOV) were also determined. Pulmonary artery systolic pressure (PASP) and tricuspid annular plane systolic excursion (TAPSE) were measured by echocardiography. A flattening VO₂ occurred in 92 patients (28.8%). PASP and TAPSE at rest were significantly higher and lower (P < 0.001), respectively. The primary outcome was the combination of all‐cause death, heart transplantation and left ventricular assist device implantation. The secondary outcome was the primary outcome plus hospitalization for cardiac reasons. In the multivariate model including peak VO₂, VE/VCO₂ slope, EOV and VO₂ trajectory, a flattening VO₂ trajectory and EOV were retained in the regression for primary (X² = 35.78, and 36.36, respectively; P < 0.001) and secondary (X² = 12.45 and 47.91, respectively; P < 0.001) outcomes.

Conclusions

Results point to a flattening VO₂ trajectory as a likely new and strong predictor of events in HF with any ejection fraction. Given the relation of right‐sided cardiac dysfunction to pulmonary hypertension, this oxygen pattern might suggest a real‐time decrease in pulmonary blood flow to the left heart.

     

左室射血分数保留的心力衰竭研究进展

心力衰竭是各种临床心血管疾病发展的终末阶段,高发生率及高病死率使其受到越来越多的关注。在美国,其总体发生率约为1.5%～2.0%,而在年龄≥65岁的人群当中,则高达6%～10%[1]。中国的一项随机调查研究选取了15518位成年人(年龄