Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.
Department of Biostatistics and Quantitative Health Sciences, Mayo Clinic, Jacksonville, Florida.
JAMA. 2023 Mar 14;329(10):801-809. doi: 10.1001/jama.2023.0675.
Reduced heart rate during exercise is common and associated with impaired aerobic capacity in heart failure with preserved ejection fraction (HFpEF), but it remains unknown if restoring exertional heart rate through atrial pacing would be beneficial.
To determine if implanting and programming a pacemaker for rate-adaptive atrial pacing would improve exercise performance in patients with HFpEF and chronotropic incompetence.
DESIGN, SETTING, AND PARTICIPANTS: Single-center, double-blind, randomized, crossover trial testing the effects of rate-adaptive atrial pacing in patients with symptomatic HFpEF and chronotropic incompetence at a tertiary referral center (Mayo Clinic) in Rochester, Minnesota. Patients were recruited between 2014 and 2022 with 16-week follow-up (last date of follow-up, May 9, 2022). Cardiac output during exercise was measured by the acetylene rebreathe technique.
A total of 32 patients were recruited; of these, 29 underwent pacemaker implantation and were randomized to atrial rate responsive pacing or no pacing first for 4 weeks, followed by a 4-week washout period and then crossover for an additional 4 weeks.
The primary end point was oxygen consumption (V̇o2) at anaerobic threshold (V̇o2,AT); secondary end points were peak V̇o2, ventilatory efficiency (V̇e/V̇co2 slope), patient-reported health status by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels.
Of the 29 patients randomized, the mean age was 66 years (SD, 9.7) and 13 (45%) were women. In the absence of pacing, peak V̇o2 and V̇o2 at anaerobic threshold (V̇o2,AT) were both correlated with peak exercise heart rate (r = 0.46-0.51, P < .02 for both). Pacing increased heart rate during low-level and peak exercise (16/min [95% CI, 10 to 23], P < .001; 14/min [95% CI, 7 to 21], P < .001), but there was no significant change in V̇o2,AT (pacing off, 10.4 [SD, 2.9] mL/kg/min; pacing on, 10.7 [SD, 2.6] mL/kg/min; absolute difference, 0.3 [95% CI, -0.5 to 1.0] mL/kg/min; P = .46), peak V̇o2, minute ventilation (V̇e)/carbon dioxide production (V̇co2) slope, KCCQ-OSS, or NT-proBNP level. Despite the increase in heart rate, atrial pacing had no significant effect on cardiac output with exercise, owing to a decrease in stroke volume (-24 mL [95% CI, -43 to -5 mL]; P = .02). Adverse events judged to be related to the pacemaker device were observed in 6 of 29 participants (21%).
In patients with HFpEF and chronotropic incompetence, implantation of a pacemaker to enhance exercise heart rate did not result in an improvement in exercise capacity and was associated with increased adverse events.
ClinicalTrials.gov Identifier: NCT02145351.
在射血分数保留的心力衰竭（HFpEF）中，运动时心率降低很常见，且与有氧运动能力受损有关，但目前尚不清楚通过心房起搏恢复运动时心率是否有益。
确定在射血分数保留的心力衰竭伴变时功能不全的患者中，植入和程控具有频率适应性的心房起搏是否会改善运动表现。
设计、地点和参与者：这是一项单中心、双盲、随机、交叉试验，在明尼苏达州罗切斯特市的梅奥诊所的三级转诊中心评估具有症状性 HFpEF 和变时功能不全的患者中具有频率适应性的心房起搏的效果。2014 年至 2022 年期间招募了患者，随访时间为 16 周（最后随访日期为 2022 年 5 月 9 日）。运动时的心输出量通过乙炔再呼吸技术测量。
共招募了 32 名患者；其中 29 名接受了起搏器植入，并随机分为心房率反应起搏组或无起搏组，首先进行 4 周的治疗，然后进行 4 周的洗脱期，然后再进行另外 4 周的交叉治疗。
主要终点是无氧阈（V̇o2,AT）时的耗氧量（V̇o2）；次要终点是峰值 V̇o2、通气效率（V̇e/V̇co2 斜率）、由堪萨斯城心肌病问卷整体总结评分（KCCQ-OSS）评估的患者报告的健康状况和 N 端脑利钠肽前体（NT-proBNP）水平。
在随机分组的 29 名患者中，平均年龄为 66 岁（标准差，9.7），13 名（45%）为女性。在没有起搏的情况下，峰值 V̇o2 和无氧阈（V̇o2,AT）时的心率均与峰值运动时的心率相关（r 值为 0.46-0.51，均 P <.02）。起搏增加了低水平和峰值运动时的心率（16 次/分钟[95%置信区间，10 至 23]，P <.001；14 次/分钟[95%置信区间，7 至 21]，P <.001），但 V̇o2,AT 没有明显变化（起搏关闭，10.4[标准差，2.9]mL/kg/min；起搏开启，10.7[标准差，2.6]mL/kg/min；绝对差异，0.3[95%置信区间，-0.5 至 1.0]mL/kg/min；P =.46），峰值 V̇o2、分钟通气量（V̇e）/二氧化碳产生（V̇co2）斜率、KCCQ-OSS 或 NT-proBNP 水平均无明显变化。尽管心率增加，但由于每搏量减少（-24 毫升[95%置信区间，-43 至-5 毫升]；P =.02），心房起搏对运动时的心输出量没有显著影响。
在射血分数保留的心力衰竭伴变时功能不全的患者中，植入起搏器以提高运动时的心率并不能改善运动能力，并且与更多的不良事件相关。
ClinicalTrials.gov 标识符：NCT02145351。
