Duke University Medical Center, Durham, NC (R.D.L., M.K.).
Duke Clinical Research Institute, Durham, NC (K.P.A., S.R.S., F.W.R.).
Circulation. 2020 Nov 3;142(18):1725-1735. doi: 10.1161/CIRCULATIONAHA.120.050304. Epub 2020 Aug 29.
Whether an initial invasive strategy in patients with stable ischemic heart disease and at least moderate ischemia improves outcomes in the setting of a history of heart failure (HF) or left ventricular dysfunction (LVD) when ejection fraction is ≥35% but <45% is unknown.
Among 5179 participants randomized into ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), all of whom had left ventricular ejection fraction (LVEF) ≥35%, we compared cardiovascular outcomes by treatment strategy in participants with a history of HF/LVD at baseline versus those without HF/LVD. Median follow-up was 3.2 years.
There were 398 (7.7%) participants with HF/LVD at baseline, of whom 177 had HF/LVEF >45%, 28 HF/LVEF 35% to 45%, and 193 LVEF 35% to 45% but no history of HF. HF/LVD was associated with more comorbidities at baseline, particularly previous myocardial infarction, stroke, and hypertension. Compared with patients without HF/LVD, participants with HF/LVD were more likely to experience a primary outcome composite of cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina, HF, or resuscitated cardiac arrest (4-year cumulative incidence rate, 22.7% versus 13.8%; cardiovascular death or myocardial infarction, 19.7% versus 12.3%; and all-cause death or HF, 15.0% versus 6.9%). Participants with HF/LVD randomized to the invasive versus conservative strategy had a lower rate of the primary outcome (17.2% versus 29.3%; difference in 4-year event rate, -12.1% [95% CI, -22.6 to -1.6%]), whereas those without HF/LVD did not (13.0% versus 14.6%; difference in 4-year event rate, -1.6% [95% CI, -3.8% to 0.7%]; interaction = 0.055). A similar differential effect was seen for the primary outcome, all-cause mortality, and cardiovascular mortality when invasive versus conservative strategy-associated outcomes were analyzed with LVEF as a continuous variable for patients with and without previous HF.
ISCHEMIA participants with stable ischemic heart disease and at least moderate ischemia with a history of HF or LVD were at increased risk for the primary outcome. In the small, high-risk subgroup with HF and LVEF 35% to 45%, an initial invasive approach was associated with better event-free survival. This result should be considered hypothesis-generating. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.
对于射血分数（LVEF）≥35%但<45%且有心力衰竭（HF）或左心室功能障碍（LVD）病史的稳定型缺血性心脏病患者，初始侵入性策略是否优于保守策略，从而改善结局，目前尚不清楚。
在 ISCHEMIA（国际比较医疗与侵入性方法对健康效果研究）中，共有 5179 名参与者被随机分配，所有参与者的 LVEF 均≥35%。我们比较了有基线 HF/LVD 病史和无 HF/LVD 病史的参与者的治疗策略对心血管结局的影响。中位随访时间为 3.2 年。
基线时有 398 名（7.7%）参与者有 HF/LVD，其中 177 名有 HF/LVEF >45%，28 名有 HF/LVEF 35%至 45%，193 名有 LVEF 35%至 45%但无 HF 病史。HF/LVD 与更多的基线合并症相关，特别是既往心肌梗死、卒中和高血压。与无 HF/LVD 的患者相比，有 HF/LVD 的患者更有可能出现心血管死亡、非致死性心肌梗死或不稳定型心绞痛、HF 或复苏性心脏骤停的主要复合终点（4 年累积发生率分别为 22.7%和 13.8%；心血管死亡或心肌梗死发生率分别为 19.7%和 12.3%；全因死亡或 HF 发生率分别为 15.0%和 6.9%）。HF/LVD 患者随机接受侵入性治疗与保守治疗，其主要终点发生率较低（17.2%和 29.3%；4 年事件发生率差异为-12.1%[-22.6%至-1.6%]），而无 HF/LVD 的患者则无差异（13.0%和 14.6%；4 年事件发生率差异为-1.6%[-3.8%至 0.7%]；交互作用=0.055）。当使用 LVEF 作为有和无既往 HF 的患者的连续变量分析侵入性与保守策略相关的结局时，主要结局、全因死亡率和心血管死亡率也出现了类似的差异效应。
有 HF 或 LVD 病史的稳定型缺血性心脏病和至少中度缺血性心脏病的 ISCHEMIA 参与者发生主要结局的风险增加。在 HF 且 LVEF 为 35%至 45%的小而高危亚组中，初始侵入性方法与无事件生存改善相关。该结果应被视为假说产生。
