Background:Chronotropic incompetence is common in heart failure with preserved ejection fraction (HFpEF) and is associated with impaired aerobic capacity. We investigated the integrity of cardiac β–receptor responsiveness, an important mechanism involved in exertional increases in HR, in HFpEF and control subjects.Methods:Thirteen carefully screened patients with HFpEF and 13 senior controls underwent exercise testing and graded isoproterenol infusion to quantify cardiac β–receptor–mediated HR responses. To limit autonomic neural influences on heart rate (HR) during isoproterenol, dexmedetomidine and glycopyrrolate were given. Isoproterenol doses were increased incrementally until HR increased by 30 beats per minute. Plasma levels of isoproterenol at each increment were measured by liquid chromatography with electrochemical detection and plotted against HR.Results:Peak VO₂ and HR (117±15 versus 156±15 beats per minute; P<0.001) were lower in HFpEF than senior controls. Cardiac β–receptor sensitivity was lower in HFpEF compared to controls (0.156±0.133 versus 0.254±0.166 beats per minute/[isoproterenol ng/mL]; P<0.001). Seven of 13 HFpEF subjects had β-receptor sensitivity similar to senior controls but still had lower peak HRs (122±14 versus 156±15 beats per minute; P<0.001).Conclusions:Contrary to our hypothesis, patients with HFpEF displayed impaired cardiac β–receptor sensitivity compared with senior controls. In the 7 out of 13 patients with HFpEF with age-appropriate β–receptor sensitivity, peak HR remained low, suggesting impaired sinus node β-receptor function may not fully account for low exercise HR response. Rather in some patients with HFpEF, chronotropic incompetence might reflect premature cessation of exercise before maximal sinus node activation.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02524145.

中文翻译：

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保留射血分数的心力衰竭中的趋性功能不全的机制。

背景：趋性功能不全在心力衰竭中常见，伴有射血分数（HFpEF）保留，并与有氧能力受损有关。我们调查了HFpEF和对照组受试者心脏β受体反应性的完整性，这是导致HR劳累性增加的重要机制。方法：13名经过仔细筛查的HFpEF患者和13名高级对照者进行了运动测试和分级异丙肾上腺素输注以量化心脏β -受体介导的HR反应。为了限制在异丙肾上腺素期间自主神经对心率（HR）的影响，给出了右美托咪定和格隆溴铵。异丙肾上腺素剂量逐渐增加，直到心率每分钟增加30次。HFpEF中的₂和HR（每分钟117±15相对于156±15搏动；P <0.001）低于高级对照组。与对照组相比，HFpEF中的心脏β-受体敏感性较低（0.156±0.133对/分钟/ [异丙肾上腺素ng / mL]/0.254±0.166搏动；P <0.001）。13名HFpEF受试者中有7名的β受体敏感性与高级对照组相似，但峰值HR较低（每分钟122±14搏动与156±15搏动；P<0.001）。结论：与我们的假设相反，HFpEF患者与高级对照组相比，心脏β-受体敏感性受损。在13名年龄适当的HFpEF患者中，有7名患者的HR峰值仍然很低，表明窦房结β受体功能受损可能不能完全解释低运动性HR反应。相反，在某些HFpEF患者中，变时功能不全可能反映了在最大窦房结激活之前过早停止运动。注册：URL：https://www.clinicaltrials.gov; 唯一标识符：NCT02524145。