Improvement of Chronotropic Incompetence after a Rehabilitation Program in Obese Patients with Coronary Artery Disease Treated with Beta-Blockers: A Practice Level Study

Special Article - Cardiac Rehabilitation

Phys Med Rehabil Int. 2018; 5(4): 1153.

Improvement of Chronotropic Incompetence after a Rehabilitation Program in Obese Patients with Coronary Artery Disease Treated with Beta-Blockers: A Practice Level Study

Gondoni LA¹*, Bertone G¹, Titon AM¹, Nibbio F¹ and Montano M²

¹IRCCS Istituto Auxologico Italiano, Unit of Cardiac Rehabilitation, Ospedale San Giuseppe, Piancavallo (VB), Italy

²Ospedale Castelli, Department of Cardiology, Verbania, Italy

*Corresponding author: Luca Alessandro Gondoni, IRCCS Istituto Auxologico Italiano, Unit of Cardiac Rehabilitation, Ospedale San Giuseppe, Piancavallo (VB), Italy

Received: August 10, 2018; Accepted: September 18, 2018; Published: September 25, 2018


Background: Resting and peak exercise heart rate (HR) predict survival in various settings of patients; the same is true for chronotropic index (CI) which is a marker for all-cause mortality. We do not have data on the effect of rehabilitation on CI in obese patients affected with coronary artery disease (CAD) and treated with beta-blockers, who represent the majority of the patients we run into in everyday practice. A cardiac rehabilitation program which includes exercise and weight loss improves autonomic balance and therefore could improve CI during an exercise stress test.

Methods: We studied 432 consecutive white obese patients (123 females – 29%), aged 59.9 ± 9.0 years, affected with clinically stable CAD, treated with beta-blockers. All the patients underwent a short (23 ± 4 days) in hospital rehabilitation program consisting, among other interventions, of physical activity and diet. A treadmill exercise stress test was performed at the beginning and the end of the hospital stay.

Results: By the end of the program besides an improvement in BMI and attained METs, all HR variables were significantly improved: resting HR decreased from 69 ± 11 to 65 ± 11 beats/min; peak HR increased from 112 ± 17 to 115 ± 19 and CI increased from 0.47 ± 0.16 to 0.52 ± 0.17 (P< 0.001 for each comparison).

Conclusions: Weight loss and exercise training improve resting and peak HR and CI in obese patients affected with CAD and permanently treated with beta-blockers.

Keywords: Chronotropic index; Coronary artery disease; BMI; Betablockers


Heart rate (HR) both at rest and as a response to exercise is a powerful predictor of survival in various settings of patients: a high resting HR independently predicts mortality in patients with coronary artery disease (CAD) as well as in healthy subjects [1-3]. Also a blunted increase in HR and, consequently, an inadequate chronotropic index (CI) during exercise are both strong predictors for sudden death in healthy subjects [2,3]; among patients with coronary disease and with congestive heart failure, chronotropic incompetence independently predicts all-cause mortality [4,5]. Considering the prognostic values of HR parameters, improving the behavior of HR during an exercise test by reducing resting values and increasing peak HR and CI should be a target of rehabilitation programs, particularly in obese patients who already have a low CI and peak HR which both contribute to their reduced exercise tolerance [6].

Obesity is a worldwide problem and its prevalence has reached epidemic proportions, particularly in patients affected with CAD. Cardiometabolic rehabilitation increases exercise tolerance and favors weight loss, reducing many parameters of cardiovascular risk [7]. A benefit of physical training and weight loss in obese subjects on heart rate recovery after exercising, which is another powerful marker for survival, has already been documented [8]. Nonetheless we have no data on CI behavior in obese patients affected with CAD. This is particularly true if we consider patients treated with beta-blockers, thus making it difficult to translate results into clinical practice, since beta-blockers remain a cornerstone of treatment in CAD also in obese subjects who have by themselves a reduced CI.

We have studied obese patients with documented CAD on chronic beta-blocker therapy, considering that also in this subset of patients HR parameters keep their clinical meaning [9]: we hypothesized that weight loss and physical training, that are both core components of cardiac rehabilitation, would ameliorate autonomic balance and therefore improve CI during an exercise stress test also in that peculiar setting of patients.

Patients and Methods

We studied 432 consecutive white obese patients (123 females – 29%), affected with CAD and chronically treated with beta-blockers. The patients signed an informed consent before participation in the rehabilitation program and before doing the exercise test.

Body weight was measured in the morning after overnight fasting and after voiding: it was checked at admission and at the end of the program. BMI was calculated dividing weight (in kilograms) by height2 (in meters). Obesity was defined as a body mass index (BMI) 30kg/m2 and was subdivided in three categories: mild obesity 30-35, moderate obesity 35-40 and severe obesity > 40kg/m2 according to the current classification. For the purpose of this study, CAD was defined as a documented history of at least one of the following: myocardial infarction, coronary artery by-pass, coronary angioplasty/stenting. Every patient was in a clinically stable condition: we excluded patients with recent (less than 4 weeks) myocardial infarction or coronary intervention. All patients were in sinus rhythm and none had a pacemaker of any kind. We also excluded patients who took other drugs that might interfere with HR such as verapamil, diltiazem, digoxin, ivabradine, and all antiarrhythmic agents. Treatment with beta-blockers was maintained throughout the rehabilitation period.

The methodology of the program represents the routine at our institution and consists, beyond psychological support and patients’ education, of a short in-hospital program of low-calorie diet and physical training. Exercise stress test was conducted on the second day of the hospital stay and was repeated again at the end of the program, after a mean period of 23 ± 4 days. Patients took their usual medications, including beta-blockers, and had a light breakfast before the test. We utilized a GE series 2000 motorized treadmill with a GE Case ECG instrumentation. We used an individualized ramp protocol that has been described before [10] and measured the intensity of exercise using metabolic equivalents (METs). Resting HR was calculated on the ECG strip in the standing position before the beginning of exercise, peak HR was calculated when effort was stopped and recovery began, and CI was calculated according to the following formula: CI = (Attained maximal HR – Resting HR) / (Predicted maximal HR – Resting HR). Predicted maximal HR was calculated by the formula 220 – age. We also used the formula proposed by Keteyian et al [11] for patients on beta-blocker treatment, which calculates predicted peak HR using the following correction: predicted peak HR = 119 + (resting HR/2) – (age/2). All our patients exercised on a treadmill and therefore we excluded the factor that corrects when a bicycle ergometer is used. Exercise tolerance was considered both as an absolute value and as the ratio between attained METs and predicted value according to the equation we previously published [10]. Each patients underwent an echocardiographic study to measure ejection fraction (EF).

Physical activity program: the intensity of the program was determined on the basis of the baseline exercise test. It entailed daily sessions (6 days a week) of aerobic activity which included 30 minute sessions of cycle-ergometer, walking at low speed for about 45 minutes (3-4 METs), and 30 minutes of low intensity strength exercise. All patients underwent a personal interview with an experienced physical trainer to individualize their activity program which was subsequently titrated to the improvement achieved.

Diet: resting energy expenditure (REE) was estimated by the Harris Benedict equation [12]. Diet was assigned by a dietician after a personal interview with the patient and mean caloric intake was set at around 85% of REE with a mean caloric deficit of 244 ± 220 kcal/day. Diet derived 50% of energy from carbohydrates, 30% from lipids, and 20% from proteins.

Statistical analysis

Continuous data are presented as mean ± standard deviation (SD) and categorical variables are presented as number and percentage. Study variables were resting HR, peak HR, and CI calculated according to both formulae as stated above. We also considered BMI and attained METs. T test for paired variables was executed to examine differences in the study variables before and after the program. To discriminate whether different categories of patients had different level of improvement we used a T test for unpaired data or one way ANOVA when the categories were more than two. As a post hoc test we used LSD. When appropriated a Chi-square test was used. We considered the improvement as expressed by the percentage variation in each of the study variables with the formula % = (Final - Baseline)/Baseline.

Data were analyzed with the SPSS V.23.0 package (SPSS, Chicago, Illinois, USA).


The mean age of our patients was 59.9 ± 9.0 years (range 36.9 – 79.7). Mean BMI was 37.7 ± 4.8 kg/m2 (range 30.0 – 54.4); 144 patients (33%) had mild obesity, while 171 (40%) had moderate obesity and 117 (27%) had severe obesity. As stated, every patient had stable CAD; 336 patients (78%) also had hypertension, 78 (18%) a history of heart failure, and 185 (43%) had diabetes.

Mean EF was 53 ± 10% (range 20 – 79%): 52 patients (12%) had severely depressed EF (<40%), 173 (40%) had mildly depressed EF (40-55%) and 205 (48%) had normal EF (>55%).

The role of several variables on baseline data was explored. Women had the same resting HR, but lower peak HR and CI (table 1). Women were also slightly older (61.7 ± 8.6 vs 59.2 ± 9.0 years; P = 0.007), had higher BMI (38.7 ± 4.8 vs 37.2 ± 4.7 Kg/m2; P = 0.003) and a lower prevalence of diabetes (34% vs 46%; P = 0.024) as compared to men. Women also had a lower exercise tolerance if considered as an absolute value, but not if the ratio between attained and predicted METs, which takes into account sex, was evaluated.