心脏变时功能不全的研究进展

心脏变时功能不全对心血管疾病的诊断和预后判断具有重要的应用价值,但是多年来这一指标在国内未受到重视,在临床工作中有关变时功能不全的信息未得到应用,造成重要医学信息丢失,现对心脏变时功能不全的研究进展予以综述。     

Chronotropic incompetence—Part II: Clinical implications

The definition of chronotropic incompetence as inadequate chronotropic response to metabolic demand is, in theory, quite satisfactory. However, the method used in clinical practice for determination of chronotropic incompetence is far from established. The determination of chronotropic incompetence has important diagnostic, therapeutic, and prognostic implications although the exact mechanism underlying chronotropic incompetence is at present unclear. From a pacing viewpoint, chronotropic incompetence is clinically relevant only when there is a functional improvement associated with rate-responsive pacing. Rate-responsive pacing has improved the physiologic approach to artificial pacing.     

Chronotropic incompetence and its relation to exercise intolerance in hypertrophic cardiomyopathy

Background

Diminished functional capacity is common in hypertrophic cardiomyopathy (HCM), although the underlying mechanisms are complicated. We studied the prevalence of chronotropic incompetence and its relation to exercise intolerance in patients with HCM.

Methods

Cardiopulmonary exercise testing was performed in 68 patients with HCM (age 44.8 ± 14.6 years, 45 males). Chronotropic incompetence was defined by chronotropic index (heart rate reserve)/(220-age-resting heart rate) and exercise capacity was assessed by peak oxygen consumption (peak Vo₂).

Results

Chronotropic incompetence was present in 50% of the patients and was associated with higher NYHA class, history of atrial fibrillation, higher fibrosis burden on cardiac MRI, and treatment with β-blockers, amiodarone and warfarin. On univariate analysis, male gender, age, NYHA class, maximal wall thickness, left atrial diameter, peak early diastolic myocardial velocity of the lateral mitral annulus, history of atrial fibrillation, presence of left ventricular outflow tract obstruction (LVOTO) at rest, and treatment with beta-blockers were related to peak Vo₂. Peak heart rate during exercise, heart rate reserve, chronotropic index, and peak systolic blood pressure were also related to peak Vo₂. On multivariate analysis male gender, atrial fibrillation, presence of LVOTO and heart rate reserve were independent predictors of exercise capacity (R² = 76.7%). A cutoff of 62 bpm for the heart rate reserve showed a negative predictive value of 100% in predicting patients with a peak Vo₂ < 80%.

Conclusions

Blunted heart rate response to exercise is common in HCM and represents an important determinant of exercise capacity.     

Chronotropic incompetence in clinical exercise testing

Chronotropic incompetence has been found to be an important predictor of obstructive coronary artery disease (CAD). However, few data define the normal heart rate response to progressive exercise and allow a clear definition of chronotropic incompetence. In this study, 312 patients who underwent an exercise stress test and coronary angiography were evaluated. The exercise heart rates of 140 normal subjects were used to define the normal mean heart rate at progressive work loads. Two standard deviations of the mean were chosen to represent a normal response at various levels of exercise. Analysis of the exercise heart rates in 172 patients who had CAD revealed 16 patients who had a peak exercise heart rate below 2 standard deviations of the mean. Of the 16 patients, 5 had 1-vessel, 5 had 2-vessel and 6 had 3-vessel CAD. Of 65 patients who had no significant ST-segment shift and who did not reach 85% of age-predicted heart rate, 13 (20%) had an inappropriately low heart rate for the work load performed. Each of the 13 patients had CAD. Of the 172 patients with CAD, those with chronotropic incompetence exercised further than the patients who did not have chronotropic incompetence (9.4 +/- 2.1 vs 7.0 +/- 3.4 METs, p less than 0.01). In conclusion, chronotropic incompetence is a relatively infrequent occurrence in an exercise test population; however, this finding, when present, is relatively specific for CAD, and may be useful in detecting patients with CAD who have an indeterminate exercise test.     

Effects of theophylline on exercise indices in a patient with chronotropic incompetence

Several investigators have documented the successful use of oral sustained-release theophylline in treating symptomatic bradycardia and sick sinus syndrome. This paper reports a case of chronotropic incompetence in which specific exercise indices, including the chronotropic response index, were used to measure the therapeutic efficacy of theophylline.     

运动试验时心脏变时功能不全影响因素的研究

目的分析平板运动试验中心脏变时功能不全的影响因素。方法回顾分析2008年1月至2011年10月于北京大学人民医院行平板运动试验并通过冠状动脉造影明确或排除冠心病的112例患者资料,根据平板运动试验中是否发生心脏变时功能不全(平板运动试验中实测最大心率<85%年龄预测最大心率)将患者分为变时功能正常组(65例)及变时性功能不全组(47例)。收集各项临床观察指标进行Logistic多因素回归分析,探寻平板运动中发生心脏变时功能不全的影响因素。结果单因素分析发现男性(p=0.016)、吸烟(p<0.001)、冠心病(p=0.004)、BM(Ip=0.047)在心脏变时功能不全组间和心脏变时功能正常组两组间存在显著性差异。二分类非条件Logistic多因素回归分析表明,吸烟(OR=3.473;95%CI1.510-7.988;p=0.003)是平板运动试验中心脏变时功能不全的独立危险因素。结论吸烟影响心脏变时功能,是平板运动试验中心脏变时功能不全发生的独立危险因素。     

Chronotropic Incompetence and Abnormal Autonomic Modulation in Ambulatory Chagas Disease Patients

Background: Chagas disease (ChD) patients might present chronotropic incompetence during exercise, although its physiopathology remains uncertain. We evaluated the heart rate (HR) response to exercise testing in ChD patients in order to determine the role of autonomic modulation and left ventricular dysfunction in the physiopathology of chronotropic incompetence. Methods: ChD ambulatory patients (n = 170) and healthy controls (n = 24) underwent a standardized protocol including Doppler echocardiography, Holter monitoring, HR variability analysis, brain natriuretic peptide (BNP) measurement, and maximal exercise testing. The chronotropic response was calculated as the percentage of predicted HR achieved and the HR increment (ΔHR) during exercise. ChD patients were divided according to the absence or presence of cardiopathy and chronotropic incompetence (<85% predicted HR). Results: Chronotropic incompetence was present in 34 (20%) of all ChD patients. The group with cardiopathy displayed reduced ΔHR (91 ± 19 bpm) during exercise in comparison with ChD patients without cardiopathy (100 ± 19 bpm). Both the values observed in ChD groups were significantly different from those of controls (112 ± 13 bpm). Exercise duration, maximal oxygen consumption, and systolic blood pressure increment were significantly reduced in patients with abnormal chronotropic response. ΔHR during the exercise was significantly correlated with markers of autonomic control of sinus node, such as rest HR (r =?0.498, P ≤ 0.001), peak HR during exercise (r = 0.775, P ≤ 0.001), minimal HR during Holter recording (r =?0.231, P = 0.003), and high‐ and low‐frequency components of short‐term HR variability (r = 0.188, P = 0.042 and r = 0.203, P = 0.027). Neither left ventricular function nor BNP levels were independently related to the presence of chronotropic incompetence. Conclusions: Chronotropic incompetence may be considered an early sign of autonomic dysfunction in ChD patients.     

Chronotropic response to exercise testing is associated with carotid atherosclerosis in healthy middle-aged men.

AIMS: Chronotropic incompetence, an attenuated heart rate (HR) response to exercise, is an independent predictor of cardiovascular mortality, but it is not known whether chronotropic incompetence is related to carotid atherosclerosis. The association between chronotropic incompetence and carotid atherosclerosis in 8567 (age 47.6+/-8.8 years) healthy men was examined. METHODS AND RESULTS: Chronotropic incompetence was defined as the failure to achieve 85% of the age-predicted maximal HR (APMHR), <80% HR reserve (HRR), and chronotropic response index (CRI). Carotid atherosclerosis was defined, using B-mode ultrasonography, as stenosis >25% and/or intima-media thickness (IMT) of >1.2 mm. In multivariable adjusted logistic regression models, the subjects who achieved less than 85% of APMHR exhibited an odds ratio (OR) of 1.72 [95% confidence intervals (CI): 1.32-2.22] for carotid atherosclerosis. Subjects with <80% of HRR were 1.45 (95% CI: 1.14-1.84) times more likely to have carotid atherosclerosis after multivariate adjustment. Also, the OR of carotid atherosclerosis across quartiles of CRI (highest to lowest) was 1.51 (95% CI: 1.10-2.09) after multivariate adjustment. CONCLUSION: These results suggest that the chronotropic response to exercise is associated with carotid atherosclerosis, independent of the established risk factors in healthy men, which could contribute to high incidence of cardiovascular diseases in subjects with chronotropic incompetence.     

运动试验变时性与冠心病相关性的研究

目的以运动试验中实达心率与年龄预测心率的比值作为变时性的一项指标,探讨其对冠心病的诊断价值。方法104例临床疑诊冠心病患者行冠脉造影、平板运动试验,得出冠心病组、对照组运动试验中变时性功能指标参考值,根据数据绘制受试者工作特性(ROC)曲线,采用配对ROC曲线下面积Z检验研究运动试验中变时性指标对冠心病的诊断效能。结果①冠心病组、对照组变时性指标有显著性差异(p<0.001);②变时性指标诊断冠心病的敏感性为63.8%,特异性为71.9%;③与传统ST段对冠心病的诊断效能相比无显著性差异(p>0.05);④将两种指标进行序列试验可以提高诊断准确率,序列试验联合特异性为86.0%,平行试验联合敏感性为87.2%。结论变时性功能可作为判断冠心病的指标,与传统的ST段指标联合应用可提高冠心病的检出率。     

The functional significance of chronotropic incompetence during dobutamine stress test

OBJECTIVE: To investigate the functional significance of chronotropic incompetence during dobutamine stress echocardiography. PATIENTS AND METHODS: The functional significance of chronotropic incompetence was evaluated during dobutamine stress echocardiography in 512 patients without beta blocker treatment who underwent dobutamine stress echocardiography (up to 40 microg/kg/min) and completed the protocol or reached the target heart rate. Mean (SD) age was 60 (12) years (313 men, 199 women). Chronotropic incompetence was defined as failure to achieve 85% of the maximum exercise heart rate predicted for age and sex (220 - age in men; 200 - age in women) at maximum dobutamine dose. RESULTS: Chronotropic incompetence occurred in 196 patients (38%). Affected patients were significantly younger, more likely to be men (both p < 0.001) and smokers (p < 0.05), had a higher prevalence of previous myocardial infarction (p < 0.005) and resting wall motion abnormalities (p < 0. 05), and had a lower resting heart rate (p < 0.001) and systolic blood pressure (p < 0.001) than patients without chronotropic incompetence, but there was no difference in the overall prevalence of ischaemia and significant coronary artery disease. By multivariate analysis, independent predictors of chronotropic incompetence were a lower resting heart rate (p < 0.001), younger age (p < 0.001), and male sex (p < 0.001). CONCLUSIONS: The relations among sex, age, and chronotropic incompetence show the need to titrate the dobutamine dose using specific data based on age and sex related heart rate responses to dobutamine rather than to an exercise stress test. Obtaining specific heart rate criteria is necessary to determine whether chronotropic incompetence represents a real failure to achieve a normal response or is the result of applying an inappropriate gold standard.     

Association between Endothelial Function and Chronotropic Incompetence in Subjects with Chronic Heart Failure Receiving Optimal Medical Therapy

Objective: Impairment of flow‐mediated, endothelium‐dependent vasodilatation (FMD) of the brachial artery identifies peripheral endothelial dysfunction in subjects with chronic congestive heart failure (CHF) and is associated with increased morbidity and mortality. To further elucidate the interaction of peripheral and central mechanisms in the syndrome of CHF, we examined the association between endothelial function and chronotropic incompetence, an emerging prognostic marker in CHF. Methods: Thirty subjects with stable New York Heart Association (NYHA) functional class II–III CHF were studied. A vascular ultrasound study was performed to measure brachial artery FMD. The percentage of age‐adjusted maximal predicted heart rate (MPHR) reached during cardiopulmonary exercise tolerance testing (CPETT) was used to assess the degree of chronotropic competence. All patients received ACE inhibitors and β‐adrenoceptor blockers. Results: Brachial artery FMD averaged 1.3 ± 2.4% and age‐adjusted % MPHR 74.1 ± 11.7%. FMD correlated with % MPHR among all patients (r = 0.60, P = 0.01). FMD and resting heart rate (RHR) did not significantly correlate (r = 0.13, P = 0.55). Conclusions: FMD, a measure of peripheral endothelial dysfunction, and % MPHR, a central determinant of cardiac output, are moderately correlated in heart failure patients receiving optimal medical therapy. Whether a cause‐effect relationship underlies this association remains to be investigated. (Echocardiography 2010;27:294‐299)     

Resting Heart Rate and Chronotropic Response to Exercise: Prognostic Implications in Heart Failure Across the Left Ventricular Ejection Fraction Spectrum

Background:

We studied the relationship between resting heart rate (HR), chronotropic response to exercise, and clinical outcomes in patients with heart failure (HF) across the spectrum of left ventricle ejection fraction (LVEF).

肥胖患者运动试验中的心脏变时性研究

目的:观察不同体质指数(BMI)的患者行平板运动试验时心脏变时性变化。方法:根据BMI将333例患者分为对照组(BMI<25)224例,肥胖组(BMI≥25)109例。统一行平板运动实验检查,分别比较2组之间心脏变时性的差别。结果:肥胖组患者运动结束后第1分钟心率下降减慢,运动峰值最大代谢当量减小,与对照组相比差异有统计学意义(P<0.05)。结论:肥胖患者心脏变时性变化异常,提示肥胖患者心脏自主神经功能紊乱。     

Atropine augmentation of treadmill exercise stress echocardiography

Objectives: Performance of exercise stress testing depends on adequate workload and is limited by patients’ inability to reach target heart rate due to noncardiac illness or medications such as beta‐blockers. This study aimed to assess the utility of atropine administration to augment the chronotropic response of patients undergoing treadmill exercise stress echocardiography. Methods: In a retrospective study, we assessed the utility of atropine administration to augment the chronotropic response in 1,396 patients undergoing treadmill exercise stress echocardiography between January 2004 and January 2009, compared with a historical control group with no atropine augmentation. Results: Atropine was well tolerated. The proportion of abnormal studies differed significantly between patients who underwent exercise with and without atropine augmentation (15% vs. 10%; P < 0.0001). Compared with the historical control group, the proportion of patients who achieved ≥85% of their target heart rates increased from 67% to 78% (P < 0.0001). Conclusions: While atropine augmentation is safe and feasible, further studies are required to determine whether it is an equivalent surrogate to achieving target heart rate through exercise alone. (Echocardiography 2011;28:1109‐1112)     

不同体质人群的心脏变时功能研究

目的观察不同体质指数人群(正常人群和肥胖人群)在运动平板试验中的心脏变时功能的差异。方法根据BMI将受试人群分为正常体重组(BMI25)192例,肥胖组(BMI≥25)210例,观察对比两组人群在运动试验过程中达到运动峰值时间,心脏变时指数,休息后2分钟心率、收缩期血压下降百分比,心率、血压恢复至运动前水平的时间等指标。结果肥胖组人群运动峰值时间较正常组提前,肥胖组人群心脏变时性不良、肥胖组人群休息后2分钟心率及血压恢复百分比较正常组减小,肥胖组心率及血压恢复至运动前水平时间较与正常组人群延长,两组间比较有显著统计学意义。结论肥胖组人群心脏变时功能异常,提示体重超标人群的心脏自主神经功能较差。     

Exercise testing in the latent phase of Chagas' disease

Exercise stress testing was performed in 50 completely asymptomatic patients in the latent phase of Chagas' disease. In 32 (64%) abnormalities were found consisting of either abnormal ST depression, exercise-induced arrhythmias, or chronotropic incompetence. The latter was determined by comparing the heart rate response to 50 age- and sex-matched control patients without serologic evidence of Chagas' disease. In the absence of an adequate control population we can only speculate as to the significance of the ST depression and arrhythmias during exercise. However, chronotropic incompetence may be a specific marker for Trypanosomal infestation in an endemic area. It probably is an early manifestation of autonomic dysfunction secondary to Chagas' disease.