University of Milano, Cardiology University Department, Heart Failure Unit, IRCCS Policlinico San Donato, Milano, Italy.
Eur J Prev Cardiol. 2020 Mar;27(5):526-535. doi: 10.1177/2047487319863506. Epub 2019 Jul 25.
Chronotropic insufficiency (CI) is defined as the inability of the heart to increase its rate commensurate with increased demand. Exercise CI is an established predictor of major adverse cardiovascular events in patients with cardiovascular diseases.
The aim of this study was to evaluate how exercise CI phenotypes different levels of cardiovascular risk and how it may better perform in defining cardiovascular risk when analysed in the context of cardiopulmonary exercise test (CPET)-derived measures and standard echocardiography in a healthy population with variable cardiovascular risk profile.
Apparently healthy individuals ( = 702, 53.8% females) with at least one major cardiovascular risk factor (MCVRF; hypertension, diabetes, tabagism, dyslipidaemia, body mass index > 25), enrolled in the Euro-EX prevention trial, underwent CPET. CI was defined as the inability to reach 80% of the chronotropic index, that is, the ratio of peak heart rate - rest heart rate/peak heart rate - age predicted maximal heart rate (AMPHR: 220 - age), they were divided into four groups according to the heart rate reserve (<80%>) and respiratory gas exchange ratio (RER; < 1.05>) as a marker of achieved maximal performance. Subjects with a RER < 1.05 ( = 103) were excluded and the final population ( = 599) was divided into CI group ( = 472) and no-CI group ( = 177).
Compared with no-CI, CI subjects were more frequently females with a history of hypertension in a high rate. CI subjects also exhibited a significantly lower peak oxygen uptake (VO) and circulatory power and an echocardiographic pattern indicative of higher left atrial volume index and left ventricular mass index. An inverse stepwise relationship between heart rate reserve and number of MCVRFs was observed (one MCVRF: 0.71 ± 0.23; two MCVRFs: 0.68 ± 0.24, three MCVRFs: 0.64 ± 0.20; four MCVRFs: 0.64 ± 0.23; five MCVRFs: 0.57 ± 18; < 0.01). In multivariate analysis the only variable found predicting CI was peak VO ( < 0.05; odds ratio 0.91; confidence interval 0.85-0.97).
In a population of apparently healthy subjects, exercise CI is common and phenotypes the progressive level of cardiovascular risk by a tight relationship with MCVRFs. CI patients exhibit some peculiar abnormal exercise gas exchange patterns (lower peak VO and exercise oscillatory ventilation) and echo-derived measures (higher left atrium size and left ventricle mass) that may well anticipate evolution toward heart failure.
变时性功能不全（CI）定义为心脏不能随着需求的增加而增加其速率。运动 CI 是心血管疾病患者发生主要不良心血管事件的既定预测因子。
本研究旨在评估运动 CI 如何在不同心血管风险水平下表现不同，以及在健康人群中，当结合心肺运动试验（CPET）衍生指标和标准超声心动图进行分析时，它如何在定义心血管风险方面表现更好，这些人群具有不同的心血管风险特征。
在 Euro-EX 预防试验中，共纳入了 702 名至少存在 1 项主要心血管危险因素（MCVRF；高血压、糖尿病、吸烟、血脂异常、体重指数＞25）的看似健康个体，这些个体接受了 CPET。CI 定义为无法达到 80%的变时指数，即最大心率与静息心率之差与最大心率与年龄预测值之比（AMPHR：220-年龄），根据心率储备（＜80%）和呼吸气体交换比（RER；＜1.05）将其分为 4 组，后者作为达到最大运动能力的标志物。RER＜1.05（n=103）的患者被排除，最终纳入 599 例患者，分为 CI 组（n=472）和非-CI 组（n=177）。
与非-CI 组相比，CI 组女性更多，且高血压病史发生率更高。CI 组的峰值摄氧量（VO）和循环动力明显降低，超声心动图显示左心房容积指数和左心室质量指数更高。心率储备与 MCVRF 数量之间存在反向逐步关系（1 项 MCVRF：0.71±0.23；2 项 MCVRF：0.68±0.24；3 项 MCVRF：0.64±0.20；4 项 MCVRF：0.64±0.23；5 项 MCVRF：0.57±0.23；＜0.01）。多变量分析发现，唯一能预测 CI 的变量是峰值 VO（＜0.05；比值比 0.91；95%置信区间 0.85-0.97）。
在一个看似健康的人群中，运动 CI 较为常见，且通过与 MCVRF 的紧密关系来表现出心血管风险的渐进水平。CI 患者表现出一些特殊的异常运动气体交换模式（较低的峰值 VO 和运动性振荡性通气）和超声心动图指标（更大的左心房和左心室质量），这可能预示着向心力衰竭的发展。
