Giannoni Alberto, Gentile Francesco, Buoncristiani Francesco, Borrelli Chiara, Sciarrone Paolo, Spiesshoefer Jens, Bramanti Francesca, Iudice Giovanni, Javaheri Shahrokh, Emdin Michele, Passino Claudio
Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy; Fondazione Toscana G. Monasterio, CNR-Regione Toscana, Pisa, Italy.
Fondazione Toscana G. Monasterio, CNR-Regione Toscana, Pisa, Italy; Pisa University Hospital, Pisa, Italy.
JACC Heart Fail. 2022 Sep;10(9):662-676. doi: 10.1016/j.jchf.2022.02.006. Epub 2022 May 4.
Novel treatments targeting in baroreflex sensitivity (BRS) and chemoreflex sensitivity (CRS) heart failure (HF) are grounded on small prognostic studies, partly performed in the pre-beta-blockade era.
This study assesses the clinical/prognostic significance of BRS and CRS in a large cohort of patients with chronic HF on modern treatments.
Outpatients with chronic HF with either reduced (≤40%) or mildly reduced left ventricular ejection fraction (LVEF) (41% to 49%) underwent BRS (SD method) and CRS to hypoxia and hypercapnia (rebreathing technique) assessment and were followed up for a composite endpoint of cardiac death, implantable cardioverter-defibrillator shock, or HF hospitalization.
A total of 425 patients were enrolled (65 ± 12 years of age, LVEF 32% [IQR: 25%-38%], 94% on beta blockers). Patients with decreased BRS (n = 96 of 267, 36%) had lower exercise tolerance and heart rate variability (P < 0.05), whereas those with increased CRS to both hypoxia and hypercapnia (n = 74 of 369, 20%) had higher plasma norepinephrine and central apneas across the 24-hour period (P < 0.01). During a median 50-month follow-up (IQR: 24-94 months), the primary endpoint occurred more often in patients with decreased BRS (log-rank: 11.64; P = 0.001), mainly for increased cardiac deaths/implantable cardioverter-defibrillator shocks, and in those with increased CRS (log-rank: 34.81; P < 0.001), mainly for increased HF hospitalizations. Patients with both abnormal BRS and CRS showed the worst outcome. Reduced BRS (HR: 2.76 [95% CI: 1.36-5.63]; P = 0.005) and increased CRS (HR: 2.91 [95% CI: 1.34-6.31]; P = 0.007) were independently associated with the primary outcome and increased risk stratification when added to standard HF prognosticators (P < 0.05).
In subjects with HF on modern treatment, abnormal BRS and CRS are frequently observed. BRS and CRS elicit autonomic imbalance, exercise limitation, unstable ventilation, and predict adverse outcomes.
针对压力反射敏感性（BRS）和化学反射敏感性（CRS）的心力衰竭（HF）新疗法基于小型预后研究，部分研究是在β受体阻滞剂应用之前的时代进行的。
本研究评估在接受现代治疗的大量慢性HF患者队列中BRS和CRS的临床/预后意义。
左心室射血分数（LVEF）降低（≤40%）或轻度降低（41%至49%）的慢性HF门诊患者接受BRS（标准差法）以及对低氧和高碳酸血症的CRS（再呼吸技术）评估，并随访心脏死亡、植入式心脏复律除颤器电击或HF住院的复合终点。
共纳入425例患者（年龄65±12岁，LVEF 32%[四分位间距：25%-38%]，94%使用β受体阻滞剂）。BRS降低的患者（267例中的96例，36%）运动耐量和心率变异性较低（P<0.05），而对低氧和高碳酸血症CRS均增加的患者（369例中的74例，20%）24小时期间血浆去甲肾上腺素水平较高且存在中枢性呼吸暂停（P<0.01）。在中位50个月的随访期（四分位间距：24-94个月）内，主要终点在BRS降低的患者中更常出现（对数秩检验：11.64；P = 0.001），主要是心脏死亡/植入式心脏复律除颤器电击增加，在CRS增加的患者中也更常出现（对数秩检验：34.81；P<0.001），主要是HF住院增加。BRS和CRS均异常的患者预后最差。BRS降低（风险比：2.76[95%置信区间：1.36-5.63]；P = 0.005）和CRS增加（风险比：2.91[95%置信区间：1.34-6.31]；P = 0.007）与主要结局独立相关，并且添加到标准HF预后指标中时增加风险分层（P<0.05）。
在接受现代治疗的HF患者中，经常观察到BRS和CRS异常。BRS和CRS引发自主神经失衡、运动受限、通气不稳定，并预测不良结局。
