The Effect Of An Expanded Long Term Periodization Exercise Training In Patients With Cardiovascular Disease
The Effect Of An Expanded Long Term Periodization Exercise Training In Patients With Cardiovascular Disease
Benefits from cardiac rehabilitation (CR) programs are evidence based and widely recognized.
 Less than 50% of people who participate in hospital-based CR programs maintain an exercise
 regimen for as long as six months after completion. Despite the benefits associated with
 regular exercise training (ET), adherence with supervised exercise-based CR remains low.

 Current exercise guidelines for CR focus on moderate intensity steady state exercises, with
 walking and cycling being the most recommended types of ET. The repetitive nature of this
 type of activity can become monotonous for the patient, affecting exercise adherence,
 compliance and training outcomes. Exercise periodization is a method typically used in sports
 training, but the impact of periodized exercise to yield optimal beneficial effects in
 cardiac patients is still unclear.

 In healthy or trained populations, periodization aims to optimize ET adaptations as compared
 with non periodized training, to prevent overtraining and to avoid plateauing of training
 adaptations. Periodized methods are considered to be superior to non periodized methods in
 trained populations and appears to be superior in inactive adults. In most of the CR programs
 there are no periodization or exercise progression during medium to long term interventions.
 Further randomized controlled trials (RCT) are necessary to evaluate long-term periodization
 outcomes.

 The purpose of this research project is twofold:

 1. To conduct a 12-month randomized control trial to evaluate the effects of a periodized
 ET regime versus a non periodized ET regime (guidelines) on VO2 peak, maximal strength,
 body composition, functionality and quality of life in cardiovascular disease patients.

 2. to differentiate the effects of a 12-month periodized ET regime versus a non periodized
 ET regime on the different components of the oxygen kinetics response and oxidative
 adaptations in cardiovascular disease patients.

 These patients will be randomized in 2 ET groups: 1) periodization; 2) non periodization.
 This experimental design will occur during 48 weeks 3 times per week with 4 assessment time
 points: M0) before starting the ET program (baseline); M1) 3 months after starting the ET;
 M2) 6 months after starting the ET program and M3) 12 months at the end of the
 community-based ET program.
Cardiac Rehabilitation (CR) of patients with Cardiovascular Disease (CVD) has been practiced
 in Europe to varying degrees since the early 1970s. CR is a comprehensive, long-term program
 involving medical evaluation, prescribed Exercise Training (ET), cardiac risk factor
 modification, education and counselling. These programs are designed to limit the physiologic
 and psychological effects of cardiac illness, reduce the risk for sudden death or
 re-infarction, control cardiac symptoms, stabilize or reverse the atherosclerotic process,
 and enhance the psychosocial and vocational status of selected patients. Furthermore, it is a
 safe, useful and an effective treatment for patients with coronary artery disease (CAD),
 particularly after myocardial infarction, but also for patients with cardiac interventions
 and chronic stable heart failure.

 Exercise adherence after a hospital-based CR program is reported to be poor with only 30% to
 60% of those who complete a phase II CR program are still exercising 6 months later and after
 12 months, up to 50 to 80% of participants failing to adhere to exercise. Despite the
 benefits associated with regular ET, adherence with supervised exercise-based CR remains low.

 A brief review of meta-analysis studies that assess the impact of different types of exercise
 in short term outcomes for participants of CR will now be presented. The findings of a
 meta-analysis in 2015 indicated that high intensity interval training (HIIT) is more
 effective than moderate continuous training (MCT) for the improvement of both VO2 peak and
 the anaerobic threshold in patients with stable CAD. The greater improvement in VO2 peak
 following HIIT compared to MCT (4.6 ± 3.1 versus 2.8 ± 2.4 ml/kg/min) is important in the
 context of a 10-25% survival advantage with every 3.5 ml/kg/min improvement in VO2 peak.

 Another meta-analysis in 2016, compared HIIT and MCT in their ability to improve patients
 aerobic exercise capacity and various cardiovascular risk factors. Ten studies with 472
 patients were included for analyses (218 HIIT, 254 MCT) and the main conclusions were that
 HIIT improves the mean VO2 peak in patients with CAD more than MCT, although MCT was
 associated with a more pronounced numerical decline in patients resting heart rate and body
 weight.

 Current CR guidelines recommend the inclusion of a standardized resistance training (RT)
 program. A recent meta-analysis of ET programs in patients with CAD revealed that the
 addition of RT training to MCT led to superior improvements in body composition, muscle
 strength, peak work capacity, and a trend for greater increases in VO2 peak. Similar to HIIT,
 RT has not been shown to compromise patient safety or program adherence.

 Less is known about central and peripheral adaptations during long term effects on HIIT, MCT
 or even aerobic combined training with RT. In 2016, a systematic review and meta-analysis
 with a total of 63 studies with 14,486 participants with CAD median follow-up of 12 months
 were included. It was concluded that exercise-based CR reduces cardiovascular mortality and
 provides important data showing reductions in hospital admissions and improvements in quality
 of life. Madssen et al, showed that a 12-month maintenance exercise program consisting of
 infrequent supervised exercise sessions did not result in improved adherence to exercise or
 increased VO2 peak in CAD patients compared to usual care. One monthly session during a year
 of HIIT was not enough to improve or maintain exercise capacity. In the literature there is a
 lack of evidence on the effects in exercise capacity, muscle strength and body composition in
 long term weekly supervised exercise sessions on a maintenance exercise program in CVD
 patients.

 Current exercise guidelines for CR focus on moderate intensity steady state exercises, with
 walking and cycling being the most recommended types of ET. Multiple training variables can
 be manipulated during exercise prescription, including repetitions, interval length, rest
 period length and intensity of resistance. In this regard, much insight could be gained from
 approaches used in sport conditioning, where exercise prescription is designed to be
 physiologically and psychologically sustainable using periodization.

 Periodization is defined as an organized cyclic program that uses planned variations in
 intensity, volume, and specificity to minimize fatigue and maximize performance outcomes. In
 healthy or trained populations, periodization aims to optimize ET adaptations as compared
 with non periodized training, to prevent overtraining and to avoid plateauing of training
 adaptations. Periodized methods are considered to be superior to non periodized methods in
 trained populations and appears to be superior in inactive adults. Interestingly, a recent
 study investigated the effect of 22 weeks of 2 different types of periodization and non
 periodization resistance training protocols on a comprehensive range of physical function and
 health outcomes in apparently healthy untrained older adults. Contrary of what was
 hypothesised, all three training models were equally effective for promoting significant
 improvements in various physical function and physiological health outcomes through
 resistance training in this population.

 In most of the CR programs there are no periodization or exercise progression during medium
 to long term interventions. Evaluate long-term periodization outcomes and assess the length
 of change observed in supervised CR programs might be of interest and necessary.

 This study will hopefully contribute to generate evidence-based exercise prescription
 approaches to prolong the ET after the end of hospital-based CR programs.

 The purpose of this research project is twofold:

 1. To conduct a 12-month randomized control trial to evaluate the effects of a periodized
 ET regime versus a non periodized ET regime (guidelines) on VO2 peak, maximal strength,
 body composition, functionality and quality of life in CVD.

 2. to differentiate the effects of a 12-month periodized ET regime versus a non periodized
 ET regime on the different components of the oxygen kinetics response and oxidative
 adaptations in CVD patients.

 The hypothesis for this study are: 1) considering that this type of periodization exerts
 higher stress on the cardiovascular and neuromuscular systems, so that there could be greater
 adaptations leading to higher increases in VO2max, muscle strength, body composition and
 functionality compared to non periodized ET regime; 2) there will be a better improvement
 microvascular O2 delivery in the exercise transient in response to periodized ET regime that
 will be associated with a faster adjustment of pulmonary VO2 kinetics than in non periodized
 group. Improvements in microvascular O2 delivery will be indicated by a better matching
 between the rate of adjustment of muscle deoxygenation relative to phase II pulmonary VO2,
 which represents a decreased reliance on O2 extraction for a given pulmonary VO2.

 STUDY DESIGN:

 A longitudinal RCT research design performed in the Cardiovascular Rehabilitation Center of
 the University of Lisbon (CRECUL) at the Lisbon University Stadium (EUL) using two distinct
 ET prescriptions (periodization vs non periodization) will be applied in cardiovascular
 disease patients. Briefly, following the informed consent process, patients will be
 randomized and stratified (by gender and age) to periodization or non periodization groups.
 The randomization code will be developed with a computer random-number generator to select
 random permuted blocks. Participants will exercise for a period of 12 months. All the same
 assessments, except the echocardiogram that will be done in M0 and M3 (for risk
 stratification), are going to be taken in 4 different time points during a year: M0 -
 baseline, M1 - 3 months after starting the ET, M2 - 6 months after starting the ET and M3 -
 12 months after starting the ET. The patients will be randomized into either one of the two
 ET group.

 Sample size was calculated (G-Power, Version 3.1.3) assuming a difference in peak oxygen
 uptake (VO2 peak) between groups of 3 ml/kg/min to be a clinical important difference with a
 standard deviation of 3.5 ml/kg/min, α=0.05, 1-β=0.80 and an expected dropout rate of 50%.
 The calculations yielded a total minimum sample size of 56 participants (28 in each group).

 The following assessments on the 4 time points will be performed at the Pulido Valente
 Hospital, Faculty of Human Kinetics - University of Lisbon (FMH-UL) and Academia de Fitness
 at EUL: Echocardiogram (Echo) (MyLab Alpha, ESAOTE); cardiopulmonary exercise test (CPET)
 (Ergostik, Geratherm Respiratory GmbH, Bad Kissingen); skeletal muscle deoxygenation dynamics
 (NIMO, Nirox srl); body composition - dual energy radiographic absorptiometry (DXA, Hologic
 Explorer-W); objective measured physical activity - accelerometer (ActiGraph GT3X+);
 functional physical fitness - Fullerton Functional Fitness Test; isometric strength -
 portable hand dynamometer JAMAR plus digital (Sammons Preston); maximal strength - 1RM and
 Quality of Life questionnaire (Short Form-36 Health Survey).

 All assessment moments will be done in 1 to 2 weeks:

 Day 1 - Echo and CPET will be performed at the Hospital; Day 2 and 3 - during the day and
 time of the ET session at the EUL, the patient will perform: functional physical fitness
 tests; maximal strength; isometric strength and Quality of Life questionnaire; Day 4 - In
 FMH-UL, the dual energy radiographic absorptiometry (DXA) exam and the activation of the
 accelerometer to measure the objective measured physical activity will be done.

 Day 5 - Submaximal CPET with the skeletal muscle deoxygenation dynamics at the Hospital.

 In order to assure the confidentiality of the participants an ID code will be attributed to
 each participant in the database and all the equipment's and sheets used. A single researcher
 will perform the database management.

 DATA ANALYSIS:

 Data will be analyzed in M0, M1, M2 and M3. It will be tested the data for normality and
 homogeneity of variance with the Shapiro Wilk and Levene's tests, respectively. Data analysis
 will be described according to the established purposes for this project (descriptive values:
 mean, standard deviation, range, % change) and comparisons of means will be used for all
 purposed outcomes intra and inter groups. Baseline characteristics between groups will be
 evaluated with oneway ANOVA. Mixed between within subjects ANOVA will be conducted in a 2
 (pre vs post ET) design to assess efficiency of the program. When a significant interaction
 is observed, t tests, or Wilcoxon signed-rank tests will be used to determine where the
 interaction occurred.

 M0 versus M1, M0 versus M2, M0 versus M3, M1 versus M2, M2 versus M3 and M1 versus M3 will be
 compared to evaluate the changes in patients and trace the necessary timespan for such
 changes using General Linear Mixed Model Analysis for repeated measures with Tukey's post hoc
 procedure for the mean comparisons. Pearson product moment correlation coefficient or
 Spearman's rank correlation coefficient will be used to study the relationship between
 different variables by group and correlation coefficients will be compared between groups.
 Statistical significance will be set at an alpha level of 0.05. Other statistical procedures
 can be done.

 Statistical analyses will be conducted using Statistical Package for the Social Sciences
 (SPSS) 22.0 (IBM SPSS Statistics, Chicago, IL, USA).
Inclusion Criteria:

 -  angiographically documented coronary artery disease in at least one major epicardial
 vessel

 -  myocardial infarction,

 -  coronary revascularization (coronary artery bypass grafting, percutaneous transluminal
 coronary angioplasty, or coronary artery stent),

 Exclusion Criteria:

 -  heart failure

 -  unstable angina pectoris

 -  heart transplants with either cardiac resynchronization therapy or implantable
 defibrillators

 -  inability to comply with guidelines for participation in exercise testing and training

 -  significant limiting and/or unstable comorbidities that would prevent full
 participation