Effects of Cardiac Rehabilitation on Functional Capacity and Cardiovascular Risk Factors in Brazilian Patients Assisted by Public Health Care: A Randomized Controlled Trial
Phase: NA
Conditions: Cardiovascular Disease, Coronary Disease
Sponsor: Federal University of Minas Gerais

 
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Cover page: 
 
TITLE 
Effects of comprehensive cardiac rehabilitation on functional capacity and 
cardiovascular risk factors in Brazilian patients assisted by public health 
care: protocol for a randomized controlled trial 
 
 
 
 
Trial registration:  
 
Clinical Trials, NCT02575976. Registered 14 October 2015. 
 
 
 
 
Methods and statistical plan 
 
 
 

 
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Methods 
Study design 
The design is a single-blinded, single-site, pragmatic, superiority RCT 
with 3 parallel arms: comprehensive CR (education and exercise) versus 
exercise-based CR (no education, as delivered in Brazil) versus wait-list control 
(i.e., no CR). Patient assessments will be undertaken pre-randomization and 
again 6 months later (in accordance with the end of CR). Mortality will be 
ascertained at 6 months and 1 year post-recruitment. Research ethics approval 
has been secured from Federal University of Minas Gerais (898.235) and York 
University (e2015 - 172).  
Setting 
This RCT will be conducted in the Brazilian city of Belo Horizonte (capital 
of the Minas Gerais state). Brazil was chosen as the initial MIC setting for 
testing because of: (1) the great burden of CVD2, (2) the availability of country-
specific CR guidelines (the only CR guidelines developed in any MICs are in 
South America and China)6, and (3) there has never been an RCT of CR (with 
any outcome) in South America to our knowledge10. 
The program where the trial will be conducted is called “The Acute 
Myocardial Infarction (AMI) Management System”, which was established in 
2009. It was developed to reduce the high level of mortality from AMI in the 
region, around 16.2%2. The program provides a continuum of care for AMI 
patients from emergency care through to secondary prevention 6 months after 
the event. The program includes CR for interested patients, however this has 
never been evaluated.  
Participants 

 
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Patients will be approached at the established AMI Sistema Único de 
Saúde unified healthcare system of the City of Belo Horizonte. Coronary artery 
disease or post-MI patients, or those who have undergone percutaneous 
coronary intervention or coronary artery bypass grafting and have been referred 
to CR will be eligible to participate in the study. The inclusion criteria are: 
patients older than 18 years old, living in the Belo Horizonte area. The exclusion 
criteria are: any comorbid physical or serious mental condition which would 
interfere with the ability to exercise according to CR clinical practice guidelines14 
(i.e., heart failure with ejection fraction less than 45%, complex ventricular 
dysrhythmia, advanced dementia, leg amputation, advanced cancer, disabling 
stroke, Parkinson’s or substance dependence), and any visual or cognitive 
condition which would preclude the participant from completing the 
questionnaires.  
Intervention Arms 
The CR program was developed based on Canadian4 and Brazilian15 CR 
guidelines. It is delivered by a multidisciplinary team including physiotherapists, 
dietitians, nurses, and physical educators. The program is exercise-based, not 
comprehensive. It is offered at no charge to patients. Participants undergo an 
intake assessment, which includes a risk factor assessment, and are re-
assessed at program end.  
The main program is 6 months in duration, with 36 1-hour exercise 
sessions offered at the following frequencies:  
1. participants come to CR for 12 sessions, 3 times a week (total of 4 weeks of 
intervention). 

 
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2. participants come to CR for 8 sessions, 2 times a week (total of 4 weeks of 
intervention). 
3. participants come to CR for 16 sessions, 1 time a week (total of 16 weeks of 
intervention).  
Each participant will receive an individualized exercise prescription 
based on a grade exercise stress test. Participants will be exercising between 
50 and 80% of heart rate reserve. At all stages of the program, patients will be 
requested to exercise in their community other days of the week, to accumulate 
30 or more minutes of physical activity at a moderate to vigorous-intensity five 
or more days per week, as recommended in the guidelines4,14,15. 
In the comprehensive CR arm, 24 education sessions will be offered, 
each of 30 minutes duration. More specifically, the education component 
consists of: 
• weekly group education sessions, which are strategically mapped based 
on patients’ information needs and sequenced to support the program 
learning outcomes16. Education sessions are delivered by a health 
educator team. See table 1 for the content of the educational curriculum. 
• a comprehensive education workbook to accompany the sessions, 
containing 20 chapters. The empirically-validated English version16,17 has 
been translated and culturally-adapted to Brazilian-Portuguese. 
Clinicians and patients have reviewed the material, and a plain language 
and clear design review was completed in preparation for this trial.  
The standard of care for Brazilian adults with CVD does not include access 
to CR for all patients, given the gross lack of capacity6. All participants will have 
follow-up appointments with their physician as deemed medically-appropriate. 

 
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Consistent with CONSORT guidelines, usual care will be described in detail for 
each participant (e.g., number of health visits - both inpatient and outpatient, 
other treatments). Participants randomized to the wait-list control arm will 
receive CR after 6-months mortality is ascertained. 
Procedure 
See Figure 1 for the trial flow diagram. Consecutive patients will be 
approached during the first physician consult after hospital discharge by a 
doctoral student, if the patient is interested in learning about the study. The 
number of patients approached and date will be recorded, as well as the 
reasons for inclusion/exclusion. With informed written consent from the patient 
and CR clearance from the physician, potentially-eligible participants will be 
scheduled to come on-site to complete pre-test assessments. Participants will 
be asked to complete a sociodemographic questionnaire, to establish the 
generalizability of the sample, among other surveys. Clinical information will be 
extracted from participants’ charts. 
Eligible participants will be randomized to one of the 3 groups. The 
randomization sequence was generated using the randomization.com website 
in random blocks of 4, with a 1:1:1 allocation ratio. To ensure allocation 
concealment, the local principal investigator (RB) has the allocation sequence 
in a password-protected file, and will only provide randomization information to 
the student once it is confirmed the participant is eligible. Due to the nature of 
the intervention, participants and the doctoral student cannot be blind to 
treatment allocation.  
The primary outcome of functional capacity and all other outcomes will 
be assessed again at 6 months post-randomization. Mortality will be 

 
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ascertained from hospital charts and family phone call at 6 months and 1-year. 
With regard to the 6 month assessment, participants will be invited to come to 
the study center to: (1) undertake the shuttle walk test as the indicator of 
functional capacity, (2) undertake assessments of secondary outcomes 
including a blood draw for lipids, and (3) complete surveys related to tertiary 
outcomes.  
A master’s student blinded to random allocation will undertake post-test 
assessments, outcome ascertainment and data entry. To minimize loss to 
follow-up, we will telephone reminders for patients to come on-site for these 
assessments. 
Measures 
Participants will be asked to complete a sociodemographic 
questionnaire. Clinical characteristics will be extracted from the medical charts, 
including sex, age, risk factors, cardiac history, cardiac test results, 
comorbidities and medications. CR session attendance will be extracted from 
program charts at post-test for participants randomized to the CR arms. 
Primary Outcome: Functional Capacity 
The primary outcome of this trial was carefully chosen. Functional 
capacity is not only important to an individual in terms of independent living and 
quality of life, it is also strongly related to health outcomes, including a graded 
inverse relationship with mortality18. 
At pre-test and 6-months later, the Incremental Shuttle walk test 
(ISWT)19 will be performed. The ISWT consists of an incremental, walking test 
where participants are required to walk up and down a 10-meter course. The 
speed of walking, which is increased by a small increment every minute (0.17 

 
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ms-l), is externally-paced and controlled by audio signals played from a tape 
recorder19. There are 12 levels in total, beginning with 0.5 ms-1, and each level 
lasts for one minute. At the end of each minute, exercise heart rate (HR) and 
rating of perceived exertion (RPE) scores will be recorded. The test is 
terminated if participants feel too breathless or fatigued to maintain the required 
speed to complete a 10-meter shuttle interval in the time allowed. After the test, 
the number of completed shuttles will be recorded and the total distance 
ambulated will be computed. Peak RPE, peak HR, time to exhaustion and the 
reason(s) for test termination will be also recorded. 
Secondary outcomes: Risk Factors 
Blood pressure will be assessed using the validated 7670-06 mobile 
stand (Welch Allyn, NY USA). Mean systolic and diastolic blood pressure values 
will be recorded, and hypertension will be considered where values exceed 
140/90 mmHg14. A weight scale and measuring tape are available at the center 
and will be used to assess anthropometrics. Those with body mass index above 
30 kg/m2 will be considered obese14. Waist circumference will be assessed at 
the superior border of the iliac crest, in accordance with standardized 
guideline14. Values greater than 102 cm in men and 88 cm in women will be 
considered indicative of central obesity20. Glycaemia and lipid values will be 
extracted from center charts. Diabetes will be considered present where fasting 
blood glucose exceeds 126 mg/dl and dyslipidemia will be considered present 
where total cholesterol values exceed 240 mg/dl14.  
Tertiary outcomes:  
Heart-health Behaviors 

 
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Smoking will be assessed via self-report (current, never, former). Other 
behaviors will be assessed using psychometrically-validated scales, as outlined 
below.  
Exercise: Participants will be asked to wear a pedometer for 7 days at 
pre and post-test and to record their daily steps on a log. Exercise will also be 
assessed using the Brazilian-Portuguese version of The Godin-Shepherd 
Leisure-Time Physical Activity Questionnaire21, which is a self-administered 
questionnaire that assesses the frequency and intensity of physical activity 
performed in a week. The respondents report the number of times they 
engaged for at least 15 minutes in vigorous, moderate and light intensity 
physical activity, considering a usual period of seven days. The frequency 
indicated by the individual is multiplied by a specific coefficient, which 
corresponds to the energy expenditure in metabolic equivalents of task (MET). 
Higher scores indicate higher levels of physical activity during leisure21. 
Medication adherence: Cardiac medication adherence will be assessed 
using the Brazilian-Portuguese version of the Morisky Medication Adherence 
Scale (MMAS-8)22. The scale contains seven questions with closed 
dichotomous (yes/no) response options and the last question is scored on a 5-
point Likert from “never” to “always”. Scores are totaled, with higher scores 
indicating greater adherence, and scores above the cut-off of 6 considered 
“adherence”.  
Diet: Diet will be assessed using the 14-item Food Frequency 
Questionnaire (FFQ) Cardiovascular Prevention23, which was designed to 
assess the consumption of foods associated with an increase or decrease in 

 
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coronary risk. A score is attributed to each food group, weighed according to 
their influence on coronary risk ranging from -36 to +4723. 
 
Depressive symptoms:   
Depressive symptoms will be measured using the Patient Health 
Questionnaire-9 (PHQ-9), which is a brief screening instrument. Frequencies of 
symptoms of major depression are solicited from patients, yielding scores 
ranging from 0 to 27, with higher scores indicating more severe symptoms. 
Severity categorizations are specified, with scores above 10 generally accepted 
as “elevated”. The PHQ-9 has been shown to have reasonable sensitivity and 
specificity for patients with CHD24. This instrument has been translated and 
validated to Portuguese25. 
Knowledge:  
Patients’ knowledge about their condition will be assessed using the 
Coronary Artery Disease Education Questionnaire II (CADE-Q II)26. The CADE-
Q II is a 31-item test that assesses cardiac patients’ level of knowledge about 
their medical condition, risk factors, exercise, nutrition, and psychosocial risk. 
Each item has 4 response options, and responses are scored from 0 to 3 (i.e., 
3- fully correct answer; 1- partially correct answer; 0- wrong answer and ‘I do 
not know’ response). The maximum total CADE-Q II score is 93. For the 
purposes of this trial, the CADE-Q II is being psychometrically-validated in 
Brazilian-Portuguese prior to administration. 
Mortality 
According to Heran et al.’s 2011 Cochrane review27, a trend towards a 
reduction in total mortality is observed in CR trials with 6-12 months follow-up. 

 
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For this reason, we will ascertain mortality at 6 months and 1 year. Given the 
lower rates of screening and treatment of CV risk factors in the middle-income 
setting, we expect mortality rates and treatment effects to be higher than in 
high-income countries where the RCTs summarized in the Cochrane review 
stemmed.   
This data will be obtained from the center’s health system records, and 
will be supplemented by family report via phone to capture deaths which may 
have occurred outside the hospital. Reason for death will be recorded where 
available. 
Sample size calculation 
Based on previous studies, we considered a clinically-important 
difference of 70 meters28 and assumed a standard deviation of 139 meters29. 
Using these values, we would require 62 participants per group, to ensure 80% 
power at the 5% significance level to detect a statistically significant difference 
in our primary outcome of functional capacity (i.e., distance walked in the 
Shuttle Test)30. Conservatively assuming a 60% recruitment rate and a 70% 
retention rate (taking into consideration attrition due to death and loss to follow-
up), we would need to approach 443 patients to achieve a sample of 267 at 
pretest and 186 at post-test (i.e., 62 per group).  
Statistical Analyses 
First, session attendance of participants in the 2 CR arms will be 
explored as a manipulation check. Second, differences in participants’ 
sociodemographic and clinical characteristics will be compared between groups 
to identify any chance difference that may have occurred despite random 
assignment, using chi-square and analysis of variance as appropriate. Third, 

 
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retention rate will be computed, and differences in the sociodemographic and 
clinical characteristics of participants retained versus lost to follow-up will be 
compared using chi-square and t-tests as appropriate. 
All statistical analyses will be performed on a per protocol basis to 
mitigate bias. For the primary outcome of functional capacity, an analysis of 
covariance (ANCOVA) will be performed, with group (i.e., comprehensive CR 
versus exercise-based CR versus wait-list control) and pre-test distance as the 
independent variables and the distance on the shuttle walk test at post-test as 
the dependent variable, adjusting for any clinical and sociodemographic biases 
based on retention. For risk factors, ANCOVAs will also be computed with post-
test scores as the dependent variable, experimental group as the independent 
variable, and pre-test scores as covariates. Post-hoc tests will be performed 
where significant group differences are observed. A Bonferroni correction will be 
applied as there are multiple secondary outcomes.   
A similar approach will be used to assess group differences in health 
behaviors, depressive symptoms and knowledge (except for smoking where a 
logistic regression model will be run). Finally, a chi-square test will be performed 
to evaluate mortality by group.