sports

Article
Periodized Aerobic Training between Thresholds Improves
Submaximal Cardiorespiratory Parameters in Octogenarians
Cristian Cofre-Bolados 1 , Félix Vidal 2 , Héctor Gutiérrez Espinoza 3, * , Ignacio Betancourt-Peters 4 ,
Pedro A. Orihuela 5 and Mikel Izquierdo 2,6

1 Laboratory of Sciences of Physical Activity, Sport and Health, Faculty of Medical Sciences, Universidad de
Santiago de Chile, Santiago 9170022, Chile; cristian.cofre@usach.cl
2 Navarrabiomed, Hospital Universitario de Navarra (HUN), Navarra Institute for Health Research (IdiSNA),
Universidad Pública de Navarra (UPNA), 31008 Pamplona, Spain; vidal.136318@e.unavarra.es (F.V.);
mikel.izquierdo@unavarra.es (M.I.)
3 Escuela de Fisioterapia, Universidad de las Americas, Quito 170504, Ecuador
4 Departamento de Ciencias Exactas, Facultad de Ingeniería, Arquitectura y Diseño, Universidad San Sebastián,
Sede Tres Pascualas, Concepción 4081339, Chile; ibetancourtp@docente.uss.cl
5 Laboratorio de Inmunología de la Reproducción, Facultad de Química y Biología, Universidad de Santiago de
Chile, Santiago 9160000, Chile; pedro.orihuela@usach.cl
6 CIBER of Frailty and Healthy Aging (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain
* Correspondence: hector.gutierrez@udla.edu.ec; Tel.: +56-992999298

Abstract: Background and Aims: The worldwide aging population is expanding, with more indi-
viduals living into their 80s. Physiological functions decline gradually with age, compounded by
sedentary lifestyles. Incorporating physical activity into daily routine is crucial for maintaining
independence. This study aimed to assess a periodized high-intensity aerobic training program
(PEZO-BT) in octogenarians, focusing on submaximal ergospirometry effects. Methods: A total of
48 non-frail octogenarian subjects (12 females, 36 males) were randomized into control and inter-
vention groups. All subjects underwent submaximal cardiopulmonary exercise testing with gas
analysis at baseline, stopping after the respiratory compensation point (RCP). Our intervention group
completed a 14-week PEZO-BT aerobic training program. The outcomes were oxygen consumption at
Citation: Cofre-Bolados, C.; Vidal, F.;
Gutiérrez Espinoza, H.; Betancourt-
first ventilatory threshold (VO2 AT), ventilatory efficiency slope (VE/VCO2 ), oxygen uptake efficiency
Peters, I.; Orihuela, P.A.; Izquierdo, slope (OUES), cardiorespiratory optimal point (COP), oxygen pulse change (∆VO2 /HR) from anaero-
M. Periodized Aerobic Training bic threshold (AT) to respiratory compensation point (RCP), and power output at anaerobic threshold
between Thresholds Improves (POAT). Results: Mixed ANOVA examined time and treatment effects. If significance emerged, post
Submaximal Cardiorespiratory hoc t-tests were used to compare significances between groups. The homogeneity of variance was
Parameters in Octogenarians. Sports assessed using Levene’s test. Chi-square tests compared ergospirometry criteria and ventilatory
2023, 11, 219. https://doi.org/ performance within groups. The mean differences at post intervention were significant in VO2 AT
10.3390/sports11110219 (p < 0.001), VE/VCO2 (p < 0.001), ∆VO2 /HR (p < 0.05), and POAT (p < 0.001), while OUES and COP
Academic Editor: François Billaut were not significant (p > 0.05). However, clinical effects were observed in the entire intervention group.
Conclusions: Training improved exercise capacity and workload. Overall, this periodic aerobic and
Received: 29 August 2023
high-intensity interval training (HIIT) program yielded significant improvements in cardiorespiratory
Revised: 18 October 2023
fitness (CRF) in previously untrained octogenarians with and without comorbidities. The findings
Accepted: 20 October 2023
suggest implications for promoting long-term healthy aging.
Published: 8 November 2023

Keywords: older adults; octogenarians; HIIT; cardiorespiratory risk; ergometry; aerobic training

Copyright: © 2023 by the authors.

Licensee MDPI, Basel, Switzerland.
This article is an open access article 1. Introduction
distributed under the terms and
Population aging is a universal process inherent to human beings. It is one of the
conditions of the Creative Commons
four “mega-trends” that are shaping the current world population, along with population
Attribution (CC BY) license (https://
growth, urbanization, and international migration. Each of these mega-trends will continue
creativecommons.org/licenses/by/
4.0/).
to significantly impact sustainable development in the coming decades [1,2].

Sports 2023, 11, 219. https://doi.org/10.3390/sports11110219 https://www.mdpi.com/journal/sports

Sports 2023, 11, 219 2 of 16

The world population is undergoing an epidemiological transition characterized by

decreased premature mortality, increased life expectancy, and gradually declining birth
rates. The octogenarian proportion has grown from 1.41% of the population in 2002 to
around 2.5% a decade later [3,4]. Physiological functions decline gradually with age, and
sedentary lifestyles are linked to reduced muscle function and cardiorespiratory fitness
(CRF) [5–7], impairing the ability to perform daily activities and maintain independence [8].
However, adequate physical exercise (PE) can significantly mitigate these age-related
declines in CRF [9,10]. Strategies to increase physical activity (PA) now focus on “lifestyle
integration”—incorporating exercise into daily routines to make it more accessible and
sustainable. The World Health Organization (WHO) recommends at least 150 min per
week of moderate aerobic exercise (MAE) or 75 min of vigorous aerobic exercise (VAE)
for adults over 65, plus muscle-strengthening activities at least twice weekly [11–14].
Moderate-to-vigorous aerobic exercise best improves maximal and submaximal aerobic
capacity, peripheral oxygen extraction, stroke volume, and arterial stiffness [15], while
high-intensity interval training (HIIT) is very effective depending on the individual’s
fitness level [16–25]. These recommendations promote active, healthy lifestyles in older
adults to improve quality of life and prevent chronic diseases [14]. In recent years, various
training programs have emerged to be tailored to older individuals’ needs and their abilities.
These programs aim to enhance overall wellbeing and functional capacity in both frail and
non-frail seniors [5,9,11,13,26–30].
Cardiopulmonary exercise testing (CPET) assessing maximal oxygen consumption
(VO2 max) is the gold standard for measuring CRF and its clinical and sports applica-
tions [31–33]. Despite its potential clinical value as a cardiovascular risk factor, CRF is
not routinely evaluated due to challenges, risks, costs, and selection bias [34]. Ironically,
excluding higher-risk individuals masks the relationship between measured CRF and
disease outcomes [35,36]. Therefore, studies have proposed submaximal CPET parameters
as alternatives to maximal testing, including oxygen consumption at ventilatory threshold
(VO2 AT) [37], VE/VECO2 slope (ventilatory class) [35], oxygen uptake efficiency slope
(OUES) [38], cardiorespiratory optimal point (COP) [39,40] or minute ventilation equiv-
alents [41,42], and oxygen pulse (VO2 /HR) at anaerobic threshold (AT) and respiratory
compensation point (RCP) [7,27,43]. Defined cutoffs distinguish normal from abnormal
CPET results [7,44]. Additionally, submaximal continuous exercise (SCE) improves respira-
tory strength, lung function, exercise tolerance, fatigue, and quality of life [45–47].
This study will assess a periodized high-intensity aerobic training program (PEZO-BT)
in octogenarians, focusing on submaximal ergospirometry effects.

2. Materials and Methods

2.1. Subjects
A total of 48 octogenarian adults, including both men and women, were included in
the study through a convenience sampling method (Table 1). Participants were individuals
who successfully completed the intervention, demonstrating over 80% attendance across
all scheduled sessions (14 weeks of training, 3 sessions per week). This cohort was selected
from an initial pool of 54 older adults. The inclusion criteria required participants to
be over 80 years old at the outset of the study, have stable cardiometabolic pathologies
as determined by medical assessment, and pass the initial medical examination, which
included a resting ECG, anamnesis, and the same submaximal ergometry.
They were selected for their participation in PA programs specifically tailored for older
adults. These programs were conducted by the Young Men’s Christian Association (YMCA)
in Santiago, Chile, with a focus on their enrollment in the Center for Adapted Exercise
(CAE) program. This program was designed to assist older adults in resuming exercise after
an 18-month period of inactivity resulting from the SARS-CoV-2 pandemic. All participants
were assessed as functionally independent and devoid of frailty, having previously engaged
in physical exercise programs at the YMCA in Santiago before the pandemic.
Sports 2023, 11, 219 3 of 16

Table 1. Characteristics (n = 48) of the octogenarian sample.

Group
Variable
Control (8M; 15F) Intervention (4M; 21F)
Age (y), mean ± SD 83.4 ± 3.5 83.3 ± 3.4
Weight (kg), mean ± SD 64.9 ± 11.1 66.4 ± 13.7
Height (m), mean ± SD 1.58 ± 7.1 1.58 ± 7.4
BMI (kg/m2 ), mean ± SD 25.9 ± 7 26.4 ± 4.7
Cardiometabolic disease, number (%) 16 (68) 18 (72)
Cardiometabolic drugs, number (%) 14 (61) 16 (64)
Values are presented as mean and standard deviation. Percentages of both groups that present with controlled, non-
complex cardiometabolic diseases, such as arterial hypertension, diabetes mellitus, insulin resistance, dyslipidemia,
or fatty liver, are included, in addition to the percentage of subjects in the sample who use cardiometabolic drugs.
(Data extracted from the medical file of each participant).

Throughout the confinement period, which was characterized by limited physical

activity opportunities, none of the participants engaged in structured or supervised exercise
sessions. Initial activity, prior to resuming their exercise program, involved a submaximal
CPET evaluation to guide their subsequent training regimen based on the assessment
outcomes. The subjects were randomly assigned into control (23) and intervention (25)
groups. The control group performed concurrent training sessions starting and finishing
with 10 min of continuous aerobic training ranging from 50 to 60% of their heart rate reserve
(HRR). Strength training was arranged in circuits of 5 exercises (leg press, leg extension,
chess press, lat row, and femoral curl) performed on the same day, completing 3 sets of
10 repetitions at 50 to 60% of a repetition maximum (RM) for each exercise, and resting
2 min between sets and 3 to 5 min after completing one lap of the circuit. The intervention
group performed a PEZO-BT program. The control and intervention groups trained 3 times
per week for a 14-week period. In addition, aerobic training was monitored with a heart
rate monitor (Polar M430). The subjects were supervised by a qualified sports scientist
coach at CAE facilities.
Informed consent was obtained from all participants, and the study protocol was
approved by the Ethics Committee of the University of Santiago. This research adhered to
the principles outlined in the Declaration of Helsinki.

2.2. Submaximal CPET Test

The participants underwent a preventive and pre-participation medical evaluation
conducted by specialist physicians in Sports Medicine and Physical Activity. This eval-
uation included the measurement of health parameters such as resting heart rate, blood
pressure, and overall musculoskeletal status for the test. Subsequently, they underwent
a submaximal CPET using a Cortex Metamax 3B gas analyzer, followed by an adapted
incremental protocol performed on a Technogym Excite (MR) cycle ergometer. The test
started with an initial load of 30 watts, with 10-watt increments every minute, maintaining
a cadence between 50 and 60 cycles per minute (Figure 1), and concluded upon reaching
the RCP, determined through graphs 6 and 9, according to the nine-panel proposal by
Wasserman (ventilatory equivalents and end-tidal pressures of oxygen and carbon dioxide,
respectively). These results allowed us to determine the AT and RCP, specifically using
graphs 6 and 9 by Wasserman, as recommended by the equipment manufacturer, along
with confirmation by a second expert. Additionally, reference submaximal parameters
associated with diagnosis, prognosis, and life expectancy were recorded, including VO2 AT,
OUES, VE/VCO2 , COP, and ∆VO2 /HR (RCP vs. AT).
Sports 2023,11,
Sports 2023, 11,219
x FOR PEER REVIEW 44 of
of 16
17

Figure 1.
Figure 1. Ramp
Ramp protocol
protocol with
with aa 10-watt
10-watt load
load increase
increase per
per minute,
minute, starting
starting at
at 30
30 watts
watts (aimed
(aimed at
at
elderly population with low aerobic power).
elderly population with low aerobic power).

2.3.
2.3. Training
Training Zones
Zones
The
The determined thresholds
thresholds were
wereused
usedtotodefine
definePEZO-BT
PEZO-BT forfor
eacheach participant
participant to
to im-
implement a progressiveand
plement a progressive andindividualized
individualizedtraining
trainingprogram.
program. This
This program
program encompasses
encompasses
the continuous aerobic
the continuous aerobic(CA)
(CA)method,
method,thethe stepped
stepped or or incremental
incremental aerobic
aerobic (IA)(IA) method,
method, and
and the HIIT method, divided into three phases based on the subdivision of
the HIIT method, divided into three phases based on the subdivision of three zones be- three zones
between
tween thethe thresholds:
thresholds: Zones
Zones A,and
A, B, B, and C [16,17,20,48–50].
C [16,17,20,48–50]. EachEach third
third is stated
is stated by heart
by heart rate
rate to control the intensity of every period (Figure
to control the intensity of every period (Figure 2). 2).

Figure 2.
Figure 2. Training
Training zones
zones between
between thresholds.
thresholds. The aerobic
aerobic training
training PEZO-BT used the individuals’
HR established for ZONE A, B, and
HR established for ZONE A, B, and C. C.
Sports 2023,11,
Sports2023, 11,219
x FOR PEER REVIEW 5 of
5 of 1716

2.4.
2.4. Training
Training
During
During the the first
first period
period(mesocycle
(mesocycleofofadaptation),
adaptation), a CA
a CA training
training was was conducted
conducted for for
6
6weeks.
weeks. This This involved
involved cyclecycle ergometer
ergometer sessions
sessions at Zone
at Zone A intensity,
A intensity, with awith a gradual
gradual pro-
progression of duration:
gression of duration: 10 to1015 to min
15 min in the
in the firstfirst 2 weeks,
2 weeks, 15 to15 25
to min
25 min in the
in the following
following 2
2weeks,
weeks,and andfinally
finally2525toto3030min
minininthe
thelast
last2 2weeks.
weeks.These
Thesesessions
sessionswerewereperformed
performed3 3times
times
per
per week.
week.
In
In the
the second
second period (mesocycle of
period (mesocycle of development),
development),lasting lasting44weeks,
weeks,thetheIAIAmethod
method
was
was implemented. Different intensity zones were alternated during 20 and 25 min ofofcycle
implemented. Different intensity zones were alternated during 20 and 25 min cycle
ergometer
ergometer sessions.
sessions. ForFor example,
example, during
during thethefirst
first22weeks,
weeks,there
therewere
wereintervals
intervalsofof5 5min
minatat
Zone
Zone A A intensity,
intensity,followed
followedby by55minminat atZone
ZoneBBintensity,
intensity,and
andthen
thenagain
againatatZone
ZoneAAand andB.B.In
the next
In the 2 weeks,
next 2 weeks,thethe
intervals
intervalswere 5 min
were 5 minat Zone
at ZoneA, A,
5 min
5 minat Zone
at ZoneB, 5B,min at Zone
5 min C, and
at Zone C,
again at Zone A. These sessions were performed
and again at Zone A. These sessions were performed 3 times per week. 3 times per week.
The
The third
third period (mesocycle of
period (mesocycle of shock)
shock)lasted
lasted44weeks
weeksand andinvolved
involvedthe theHIIT
HIITmethod.
method.
The sessions were performed at Zone C intensity and recovery at
The sessions were performed at Zone C intensity and recovery at Zone A intensity. During Zone A intensity. During
the
the first 2 weeks, there were intervals of 30 s at Zone C, followed by 1 min below ZoneZone
first 2 weeks, there were intervals of 30 s at Zone C, followed by 1 min below A,
A, repeated
repeated 5 times.
5 times. In the
In the next
next 2 weeks,
2 weeks, thethe intervals
intervals were were
1 min1 min at Zone
at Zone C, followed
C, followed by 2by
2min
minbelow
below Zone
Zone A, A,
alsoalso repeated
repeated 5 times.
5 times. TheseThese sessions
sessions were conducted
were conducted 2 times2pertimes
week,per
week,
with awith a minimum
minimum rest period
rest period of 72 hof 72 h (Figure
(Figure 3). 3).

Figure 3.
Figure 3. Overview of the training
training program
program of
of Periodization
PeriodizationZone
Zonebetween
betweenThresholds
Thresholds(PEZO-BT).
(PEZO-BT).

2.5.
2.5. Statistical Analysis
Statistical Analysis
Statistical
Statistical analyses
analyses were
were performed
performedusing usingRR(4.1.0),
(4.1.0),to
totest
testthe
thehypotheses
hypothesesof ofinterest.
interest.A
mixed
A mixed ANOVA
ANOVA analysis was
analysis considered,
was considered, with time
with as the
time within-subject
as the within-subject factor, considering
factor, consid-
2ering
levels (2 measurements,
2 levels pre and
(2 measurements, prepost), and treatment
and post), (group(group
and treatment type) type)
as theas between-subject
the between-
factor,
subjectwhich
factor,also
whichhadalso
2 levels
had 2(control group and
levels (control groupexperimental
and experimentalgroup). It wasItexamined
group). was ex-
whether the interaction effects, and then the main effects, were significant
amined whether the interaction effects, and then the main effects, were significant accord- according to the
ANOVA
ing to the ANOVA analysis. The main effects of both the treatment and time allowed us toif
analysis. The main effects of both the treatment and time allowed us to assess
there
assesswas an influence
if there of these of
was an influence factors
theseon the dependent
factors variables,
on the dependent while the
variables, interaction
while the in-
effect was associated with whether the influence of one factor
teraction effect was associated with whether the influence of one factor depended ondepended on the level
theof
the other.
level of the The size of
other. thesize
The effect
of (SE) associated
the effect with each effect
(SE) associated was obtained
with each effect wasthroughobtained the
results
throughofthe etaresults
squared. Values
of eta between
squared. 0.01between
Values and 0.059 areand
0.01 considered
0.059 aresmall effect, small
considered values
between 0.06 and
effect, values 0.0139
between areand
0.06 considered
0.0139 are medium effect,
considered and values
medium over
effect, and 0.14 are considered
values over 0.14
large effect.
are considered large effect.
If
If significant effects were
significant effects were found,
found, postpost hoc
hoctests
testsofofmeans
means(t-tests)
(t-tests)were
weresubsequently
subsequently
conducted, comparing the levels of their respective factors, and exploring
conducted, comparing the levels of their respective factors, and exploring the differences. the differences.
Bonferroni correction was applied for significance, with a significance
Bonferroni correction was applied for significance, with a significance level set at 5%. level set at 5%.Prior
Prior
to analysis, the homogeneity of variances across groups was checked using Levene’s test
Sports 2023, 11, 219 6 of 16

separately for the pre and post time points. Additionally, a chi-square test, considering Yates’
continuity correction, was performed to compare ergospirometry criteria and ventilatory
performance within the control and intervention groups based on contingency tables.

3. Results
All subjects completed the 14-week intervention, and all subjects of the control and
intervention groups were evaluated. The results are presented in box plots to display the
minimum, first quartile, median, third quartile, and maximum values of the submaximal
variables of the subjects. Also, a contingency table was used to investigate the presence
of an association or independence between variables by comparing the observed frequen-
cies with the expected frequencies (Table 2). This analysis facilitated the classification of
subjects as either normal or altered, along with the assignment of their corresponding
performance scores.

Table 2. The table shows the clinical differences between the two groups, classifying the variables as
either normal or altered.

Group Differences
Control Intervention
Variable Category Pre Mean Post Mean χ2 p Pre Mean Post Mean χ2 p
(SD) (SD) (SD) (SD)

VO2 AT <11 altered 17 (73.9) 16 (69.5) 10 (40) 4 (16)

0 0.99 4.477 0.034
(mL/kg/min) ≥11 normal 6 (26.1) 7 (30.5) 15 (60) 21 (84)

VE/VCO2 >34 altered 9 (39) 8 (34.7) 9 (36) 3 (12)

0 0.99 3.315 0.069
(L/min) ≤34 normal 14 (61) 15 (65.3) 16 (64) 22 (88)

OUES <1550 altered 21 (91.3) 6 (26) 15 (60) 6 (24)

0.01 0.971 3.299 0.069
(mL/min) ≥1550 normal 2 (8.7) 17 (74) 10 (40) 19 (76)
>30 altered 11 (47.8) 13 (56.5) 11 (44) 1 (4)
COP (L/min) 0 0.99 0.015 0.902
≤30 normal 12 (52.2) 10 (43.5) 14 (56) 24 (96)

∆VO2 /HR <0 altered 14 (61) 13 (57) 9 (36) 7 (28)

0.256 0.613 0 0.99
RCP vs. AT ≥0 normal 9 (39) 10 (43) 16 (64) 18 (72)
VO2 AT (mL/kg/min), VO2 at AT; VE/VCO2 (L/min), ventilatory class (L/min); OUES, oxygen uptake efficiency
slope (mL/min); COP, cardiorespiratory optimal point(L/min); ∆VO2 /HR RCP vs. AT, difference between
oxygen pulse at RCP and AT. The submaximal variables are categorized as altered or normal according with
their cutoff points. The ventilatory performance score was derived from the sum of abnormal criteria of each
submaximal variable.

3.1. Ergospirometry Submaximal Variables

The following data are presented in box plots (Figures 4–9), where the interested
variables were analyzed. The control and experimental groups were compared in the pre
and post period.
Sports 2023,11,
Sports 2023, 11,219
x FOR PEER REVIEW 77 of
of 16
17
Sports 2023, 11, x FOR PEER REVIEW 7 of 17

Figure 4.
Figure 4. Absolute
Absolute changes
changes in
in VO
VO2 at
at ATAT after
after 14
14 weeks
weeks of
of intervention;
intervention; ●• represents
represents outlier
outlier data.
data.
Figure 4. Absolute
Values are
are changes
expressed in VO22 at***AT
inmL/kg/min.
mL/kg/min. pp<after 14 weeks of intervention; ● represents outlier data.
0.001.
Values expressed in *** < 0.001.
Values are expressed in mL/kg/min. *** p < 0.001.

Figure 5. Absolute changes in ventilatory class after 14 weeks of intervention; ● represents outlier
Figure
Figure 5. Absolute
5. Absolute
data. Values changesinin
changes
are expressed inL/min.
ventilatory
ventilatory class
*** p <class after 14
after
0.001. 14 weeks
weeks of
of intervention;
intervention; ● represents outlier
• represents outlier
data. Values
data. Values are
are expressed
expressed in
in L/min.
L/min. ***
*** pp <<0.001.
0.001.
Sports 2023,11,
Sports2023, 11,219 8 of1716
Sports 2023, 11, xxFOR
FORPEER
PEERREVIEW
REVIEW 8 8ofof 17

Figure 6.
Figure 6. Absolute
Absolute changes
changes in
in OUES
OUES after
after 14
14weeks
weeksof
ofintervention;
intervention;●•represents
representsoutlier
outlierdata.
data.Values
Values
Figure
are 6. Absolute
expressed in changes in OUES after 14 weeks of intervention; ● represents outlier data. Values
L/min.
are expressed in L/min.
are expressed in L/min.

Figure 7. Absolute changes in ∆VO2/HR (RCP vs. AT) after 14 weeks of intervention; ● represents
outlier data.
Figure 7. Values changes
7. Absolute
Absolute are expressed
in∆VO
∆VOas 2the
/HRdifference
(RCP vs.in mL-beats
AT) VO2/HR
after 14ofweeks at RCP and AT.
of intervention; ● *represents
p < 0.05.
Figure changes in 2 /HR (RCP vs. AT) after 14 weeks of intervention; • represents
outlier data.
outlier data. Values
Valuesare
areexpressed
expressedas
asthethedifference
differenceininmL-beats
mL-beatsofofVO 2/HR at RCP and AT. * p < 0.05.
VO/HR at RCP and AT. * p < 0.05.
2
Sports
Sports 2023,11,
Sports2023,
2023, 11,219
11, xx FOR
FOR PEER
PEER REVIEW 9 of
9 9of of
1716
17

Figure 8.
8. Absolute changes in COP after 14 weeks of intervention; ●•represents outlier data. Values
Figure 8. Absolute
Figure Absolute changes
changes in
in COP
COP after
after 14
14 weeks
weeks of
of intervention;
intervention; ● represents
representsoutlier
outlierdata.
data. Values
Values
are
are expressed in L/min.
are expressed
expressedin
inL/min.
L/min.

Figure 9. Absolute changes in power output after 14 weeks of intervention; ● represents outlier data.
Figure 9.
Values
Figure 9. Absolute
are changes
expressed in power
in Watts. output after 14 weeks of intervention;
*** p < 0.001. intervention; ●
• represents outlier data.
Values are expressed in Watts. *** p < 0.001.
Values are expressed in Watts. *** p < 0.001.
3.1.1. VO2AT
3.1.1. VO
3.1.1.The AT
VO22interaction
AT effect, primary effects of treatment, and time were significant: (p <
0.001,The
SEinteraction
The 0.04) andeffect,
=interaction (peffect,primary
= 0.006, SE =effects
primary effects
0.145); of(ptreatment,
of SEand
treatment,
< 0.001, time time
and
= 0.055), were significant:
were (p <were
significant:
respectively. There 0.001,
(p <
SE =
0.001,
no 0.04)
SE =and
statistical (pand
0.04) = 0.006,
differences (p =inSEthe= pre
0.006, 0.145);
SE =period(p <(p0.001,
0.145); SE while
(p= <0.155) =SE
0.001, 0.055),
= the respectively.
0.055), There
postrespectively.
period showed were
There no
were
signif-
statistical
icant differences
differences
no statistical in the
(p < 0.001).
differences pre period
Thepre
in the control (p
period =
group0.155)
(p = had while the
an while
0.155) averagepost period
theincrease showed
of 1.67%
post period significant
whilesignif-
showed the
differences
experimental
icant differences(pgroup
< 0.001).
(p <had The control
an increase
0.001). The ofgroup
control 14.4%.
group had anan
had average
average increase
increaseofof1.67%
1.67%while
while the
the
experimental
experimental groupgroup hadhad anan increase
increaseof of14.4%.
14.4%.
3.1.2. Ventilatory Class (VE/VCO2)
3.1.2. Ventilatory Class (VE/VCO2 )
3.1.2.The
Ventilatory
interactionClass (VE/VCO
effect 2)
and primary effects of the treatment were not significant: (p >
The
0.05, The interaction
SE = interaction
0.007) and (peffect and
> 0.05, primary
SEprimary
= 0.05),effects of the treatment
respectively. were not significant: (p > 0.05,
effect and effects of theTime showed
treatment significant
were changes
not significant: (p >
SE = 0.007) and (p > 0.05, SE = 0.05), respectively. Time showed significant changes
0.05, SE = 0.007) and (p > 0.05, SE = 0.05), respectively. Time showed significant changes (p
Sports 2023, 11, 219 10 of 16

(p < 0.001, SE = 0.056). There were no statistical differences in the pre period (p = 0.0572)
while the post period show significant differences (p < 0.001). The control group had an
average decrease of 2.95% while the experimental group had a decrease of 6.39%.

3.1.3. Oxygen Uptake Efficiency Slope (OUES)

The interaction effect and primary effects were not significant: (p > 0.05, SE = 0.054) and
(p > 0.05, SE = 0.102), respectively. However, time showed significant changes (p < 0.001,
SE = 0.361). There were no statistical differences in the pre or post period: (p = 0.789) and
(p = 0.636), respectively. The control group had an average increase of 11.15% while the
experimental group had an increase of 5.48%.

3.1.4. Delta Oxygen Pulse (∆VO2 /HR RCP vs. AT)

The interaction effect, the primary effects, and time were not significant: (p > 0.05,
SE = 0.013), (p > 0.05, SE = 0.102) and (p < 0.001, SE = 0.037), respectively. There were
no statistical differences in the pre period (p = 0.1) while the post period showed signif-
icant changes (p < 0.05). The control group had an average increase of 1.93% while the
experimental group has an increase of 9.85%.

3.1.5. Cardiopulmonary Optimal Point (COP)

The interaction effect was significant (p < 0.05, SE = 0.083). The primary effect was
not significant (p > 0.05, SE = 0.218), while time showed significant changes (p < 0.001,
SE = 0126). There were no statistical differences in the pre or post period: (p = 0.622) and
(p = 0.347), respectively. The control group had an average decrease of 1.08% while the
experimental group had a decrease of 12.15%.

3.1.6. Power Output at AT (POAT)

The interaction effect, the primary effects, and time showed significant changes:
(p < 0.001, SE = 0.260), (p = 0.006, SE = 0.181) and (p < 0.001, SE = 0.260), respectively.
There were no statistical differences in the pre period (p = 1.4) while the post period pre-
sented statistical differences (p < 0.001). The control group had an average decrease of
0.62% while the experimental group has an increase of 31.6%.

3.2. Contingence Table

Comparison of ergospirometry criteria and ventilatory performance within the control
and intervention groups.

4. Discussion
No previous study has examined the impact of a periodized aerobic endurance training
approach within the PEZO-BT zone on CRF, determined by analyzing submaximal param-
eters during CPET, stopped at the RCP in elderly individuals of both sexes with comor-
bidities. Here, we show that 14 weeks of CA, combining IA with integrated HIIT, yielded
positive changes in CRF. This was evidenced by enhancements in VO2 AT, VE/VCO2 ,
OUES, COP, ∆VO2 /HR RCP vs. AT, and POAT, providing a potential strategy to counteract
established age-related physiological declines in untrained octogenarians.
CRF can be assessed using submaximal parameters with comparable predictive
strength for morbidity and mortality as VO2 max [7,40,47,49,51–54]. Previous studies [55]
reported that short-term, low-volume aerobic training with HIIT (2–8 weeks) improved
peakVO2 (~4–13%) in sedentary and recreationally active healthy adults, while a 4-week
HIIT program increased peak VO2 (9.6%) and anaerobic threshold (13%) in healthy older
adults. Similarly, in our study, VO2 AT increased by 14%. Values below 11 mL/kg/min
are considered high-risk for surgical mortality [37], suggesting potential broader impli-
cations for healthy aging, as improved CRF is associated with lower all-cause mortality
and cardiovascular events. Although not all subjects in the intervention group showed
significant changes, there were notable improvements in their performance scores. The
Sports 2023, 11, 219 11 of 16

percentage of individuals with no limitation increased from 8% to 60%, those with moderate
limitation decreased from 64% to 36%, and those with severe limitation decreased from
28% to 4% (p < 0.05). In contrast, the control group exhibited no change in individuals with
no limitation (0% both pre and post assessment), an increase from 47.8% to 69.5% in those
with moderate limitation, and a decrease from 52.2% to 30.4% in individuals with severe
limitation (p < 0.05).
The VE/VCO2 slope reflects exercise tolerance and predicts mortality in heart failure
patients [56]. Regular endurance training can improve ventilatory efficiency during exercise,
potentially by reducing peripheral chemoreceptor sensitivity and lowering the VE/VCO2
slope [57]. Slope values exceeding 34 are associated with an increased risk of mortality [58].
In our study, the VE/VCO2 slope significantly decreased from 34.4 to 33.25, falling below
the slope threshold of 34. Initially, nine subjects had an abnormal VE/VCO2 slope, but after
the training period, only three retained this abnormality. Recently, the VE/VCO2 slope has
been proposed as an alternative assessment for research involving individuals with health-
or age-related limitations [59].
A meta-analysis in heart failure patients with preserved ejection fraction found that
HIIT did not result in improvements in VE/VCO2 slopes [60], which contrasts with our
findings. It is important to note that exercise duration varied across studies, which could
potentially influence outcomes [61,62]. In our experimental group, the percentage of in-
dividuals with an abnormal slope decreased from 36% to 12%. In a 12-week study on
HIIT that examined improvements in mitochondrial bioenergetics among heart failure
patients, pronounced increases in OUES were observed after the intervention. This variable
represents the relationship between ventilation per minute and oxygen uptake during incre-
mental exercise, encompassing both respiratory function and musculoskeletal performance
within a single index. In contrast, the control group received only medical counseling with-
out exercise [63]. However, it is important to note that our study did not find a significant
difference in OUES changes post training between the experimental and control groups.
OUES represents total body efficiency providing a comprehensive view of physiological
efficiency, not limited to peripheral efficiency alone. In contrast to the VE/VCO2 ratio,
which primarily considers pulmonary conditions, this distinction highlights the differences
between these two variables [7].
The oxygen pulse serves as a metabolic surrogate for stroke volume, which typically
increases and then stabilizes during exercise. Premature flattening of the VO2 /HR curve
and a decrease in the oxygen pulse in later stages of exercise indicate inadequate cardiac
performance relative to increased effort demands [64]. In a study of U.S. veterans, changes
in the oxygen pulse occurred concurrently with alterations in peripheral endothelial func-
tion and smooth muscle activity following an aerobic training program [65]. These findings
align with our study, where the intervention group improved the oxygen pulse delta be-
tween CRP and AT by almost 10% (9.85%), while the control group improved by only
1.85%. The development of myocardial ischemia during exercise may result in a reduction
in stroke volume, leading to premature flattening of the O2 pulse curve. A descending O2
curve has been suggested to indicate the presence of exercise-induced myocardial ischemia,
assessed through myocardial perfusion imaging [66], thus the association between myocar-
dial fibrosis and an anomaly in the O2 pulse has also been demonstrated [67]. Given the
potential presence of many of the pathological conditions studied and their association
with older populations, particularly octogenarians, the delta in VO2 /HR between RCP and
AT has been utilized. The absence of a difference in favor of the RCP value or even a drop
in the oxygen pulse at RCP vs. AT is considered abnormal [68].
COP represents the integration of the circulatory and pulmonary systems [69]. A study
involving 3331 individuals defined COP categories with cutoffs: <22 L/min, 22–30 L/min,
and >30 L/min. COP > 30 L/min strongly and independently predicted all-cause mortality,
either alone or in conjunction with lower VO2 max [39]. Following the intervention, our
experimental group had fewer subjects with COP alterations (reducing from 11 to 4),
whereas the control group experienced an increase (from 11 to 13) in individuals with COP
Sports 2023, 11, 219 12 of 16

> 30 L/min. An earlier study [40] delineated that a high COP, either independently or
in conjunction with VO2 max, could serve as a robust predictor for all-cause mortality in
community-residing adults, whether apparently healthy or afflicted with chronic conditions.
COP, a submaximal prognostic index, offers a convenient adjunct to CPET assessment,
particularly valuable for individuals unable or unwilling to attain maximal exertion, as
observed in this investigation. Consequently, the COP index within the intervention group
exhibited a substantial reduction from an initial 44% impairment (11 subjects) to a mere 4%
(1 subject) post-intervention.
Furthermore, we have integrated POAT as an indicator of mechanical efficiency,
concomitant with enhancements in the submaximal parameters. A meta-analysis [70]
ascertained that variables such as VE/VCO2 slope, OUES, maximal oxygen pulse, and
respiratory exchange ratio (RER) responded comparably to both MAE and HIIT. These
findings align with a systematic review encompassing patients with coronary disease, both
with and without reduced ejection fraction [71].
As far as we know, no prior study has examined the effects of an octogenarian train-
ing program on these six selected submaximal parameters. We report that 14 weeks of
training had a positive influence on submaximal parameters, likely through cardiorespira-
tory and mitochondrial bioenergetic adaptations explained by the Wasserman model [33].
Additionally, our findings suggest specific or integrated systemic adaptations of the res-
piratory, cardiovascular, and muscular systems, as represented in the theoretical model
adaptation we propose. This adaptation aims to elucidate the interdependence of muscle
tissue, the heart, the lungs, and their respective physiological systems, with each of the
selected parameters.
Our findings provide a potential strategy to counteract the physiological age-related
declines established in octogenarians with illnesses, aiming to restore parameters within
normal ranges and consequently promote efficient individual and integrated functioning
of the respiratory, cardiovascular, and muscular systems, as postulated by the model. This
would constitute a theoretical contribution from our study.
A specific program of continuous aerobic training in the VO2 AT zone [51] and HIIT [72]
in the CRP zone has been shown to increase submaximal parameters, offering numerous
benefits for cardiorespiratory fitness and overall health. The combination of both methods
and their physiological adaptations enhances the overall effectiveness of the training
program. Our study reveals that the training program increases VO2 AT and improves
other submaximal parameters, along with exercise workload capacity.
Previous studies have demonstrated that short-term, 2- to 8-week HIIT programs
effectively increased peak VO2 (by approximately 4–13%) in sedentary and recreationally
active adults [55,73,74]. These findings hold significant implications for healthy aging, as
improved cardiorespiratory fitness is associated with reduced cardiovascular and all-cause
mortality, along with enhancements in cardiorespiratory components [75,76].
However, there are limitations to this study. Firstly, the sample size was relatively
small. Future research should consider larger sample sizes, as a larger sample may provide
a more accurate representation of the differences between the control and experimental
groups, especially for variables that did not change significantly during the 14-week
intervention. Secondly, we did not control for the nutritional and dietary status of the
participants, which could potentially influence the impact of training. Factors such as
digestive pathologies, calorie intake, protein percentage, and hydration status should be
considered in future investigations.

5. Conclusions
This study examined the effects of a 14-week periodized aerobic training program
that incorporated HIIT on octogenarians of both sexes with comorbidities. The training
had a positive impact on submaximal cardiopulmonary exercise test parameters, including
oxygen consumption at the ventilatory threshold, slope of ventilatory efficiency, slope
of oxygen absorption efficiency, cardiorespiratory sweet spot, oxygen pulse change from
Sports 2023, 11, 219 13 of 16

anaerobic threshold to respiratory compensation point, and output power at anaerobic

threshold. These improvements likely resulted from cardiorespiratory and mitochondrial
adaptations, providing a strategy to counteract age-related physical declines. The training
increased exercise capacity and workload. Overall, this periodic aerobic program and
HIIT produced significant improvements in cardiovascular fitness in previously untrained
octogenarians with and without comorbidities. Our findings suggest implications for
promoting long-term healthy aging.

6. Practical Applications
This study was not conducted at our laboratory facilities; instead, it was performed
and controlled at an exercise center dedicated to elderly individuals (CAE), where the
subjects trained daily. This demonstrates the real-world applicability of our PEZO-BT
program. We utilized ergospirometry to determine the ventilatory thresholds, but it is
worth noting that low-cost equipment and alternative methods, such as lactate curve
analysis or the talk test, are currently available for threshold determination.

Author Contributions: C.C.-B. was responsible for the conceptualization, funding, project manage-
ment, methodology, data preservation, writing, original draft, review, and editing. F.V. was responsi-
ble for the conceptualization, funding, methodology, administration of the project, the methodology
and statistical analysis, the review, and the editing. I.B.-P. was responsible for the statistical analysis.
H.G.E. was responsible for conceptualization, revision, and editing. P.A.O. was responsible for
revision and editing M.I. was responsible for conceptualization, data preservation, writing, review,
and editing. All authors have read and agreed to the published version of the manuscript.
Funding: This research received resources from the Vicerrectoria for Research, Development and
Innovation of the University of Santiago de Chile. Dicyt, código 022087CB_DAS, categoría Dicyt
Asociativo.
Institutional Review Board Statement: The study was conducted in accordance with the Declaration
of Helsinki and approved by the Comté de Ética of the University of Santiago de Chile (293/2020 on
24 July 2020).
Informed Consent Statement: Informed consent was obtained from all subjects involved in the
study. Consent has been obtained from the patients to publish this paper.
Data Availability Statement: The datasets generated and/or analyzed during the current study
are not publicly available due the terms of consent/assent to which the participants agreed but are
available from the corresponding author on reasonable request. Please contact the corresponding
author to discuss availability of data and materials.
Acknowledgments: To the Vicerrectoria for Research, Development, and Innovation of the University
of Santiago de Chile. Dicyt, código 022087CB_DAS, categoría Dicyt Asociativo. Vicerrectoría de
Investigación y Desarrollo, Universidad de Santiago de Chile, USACH, Chile.
Conflicts of Interest: The authors declare no conflict of interest.

References
1. United Nations. World Population Ageing 2019 (st/esa/ser. a/444); Department of Economic and Social Affairs: New York, NY,
USA, 2020.
2. Courel-Ibanez, J.; Buendia-Romero, A.; Pallares, J.G.; Garcia-Conesa, S.; Martinez-Cava, A.; Izquierdo, M. Impact of Tailored
Multicomponent Exercise for Preventing Weakness and Falls on Nursing Home Residents’ Functional Capacity. J. Am. Med. Dir.
Assoc. 2022, 23, 98–104.e103. [CrossRef]
3. Valdivia, G.; Dominguez, A.L.A. Población de 80 y más años en Chile: Una visión preliminar desde el punto de vista epi-
demiológico. Revista Médica Clínica Las Condes 2012, 23, 5–12. [CrossRef]
4. Departamento de Estadísticas e Información de Salud. Población ine por Grupo Etario. Available online: https://deis.minsal.cl/
(accessed on 25 December 2021).
5. Izquierdo, M.; Duque, G.; Morley, J.E. Physical activity guidelines for older people: Knowledge gaps and future directions. Lancet
Healthy Longev. 2021, 2, e380–e383. [CrossRef] [PubMed]
6. Naruse, M.; Trappe, S.; Trappe, T.A. Human skeletal muscle-specific atrophy with aging: A comprehensive review. J. Appl. Physiol.
2023, 134, 900–914. [CrossRef] [PubMed]
Sports 2023, 11, 219 14 of 16

7. Cofre-Bolados, C.; Ferrari, G.; Valdivia-Moral, P.; Vidal-Diaz, F.; Ramirez-Velez, R.; Izquierdo-Redin, M. Sub Maximal Ergospirom-
etry Parameters in Untrained Non-Frail Octogenarian Subjects. Medicina (Kaunas) 2022, 58, 378. [CrossRef] [PubMed]
8. Fernandez-Garcia, A.I.; Moradell, A.; Navarrete-Villanueva, D.; Subias-Perie, J.; Perez-Gomez, J.; Ara, I.; Gonzalez-Gross, M.;
Casajus, J.A.; Vicente-Rodriguez, G.; Gomez-Cabello, A. Effects of Multicomponent Training Followed by a Detraining Period on
Frailty Level and Functional Capacity of Older Adults with or at Risk of Frailty: Results of 10-Month Quasi-Experimental Study.
Int. J. Environ. Res. Public Health 2022, 19, 12417. [CrossRef] [PubMed]
9. Cadore, E.L.; Casas-Herrero, A.; Zambom-Ferraresi, F.; Idoate, F.; Millor, N.; Gomez, M.; Rodriguez-Manas, L.; Izquierdo, M.
Multicomponent exercises including muscle power training enhance muscle mass, power output, and functional outcomes in
institutionalized frail nonagenarians. Age (Dordr.) 2014, 36, 773–785. [CrossRef]
10. Trappe, S.; Hayes, E.; Galpin, A.; Kaminsky, L.; Jemiolo, B.; Fink, W.; Trappe, T.; Jansson, A.; Gustafsson, T.; Tesch, P. New records
in aerobic power among octogenarian lifelong endurance athletes. J. Appl. Physiol. 2013, 114, 3–10. [CrossRef]
11. Casas-Herrero, A.; Anton-Rodrigo, I.; Zambom-Ferraresi, F.; Saez de Asteasu, M.L.; Martinez-Velilla, N.; Elexpuru-Estomba,
J.; Marin-Epelde, I.; Ramon-Espinoza, F.; Petidier-Torregrosa, R.; Sanchez-Sanchez, J.L.; et al. Effect of a multicomponent
exercise programme (VIVIFRAIL) on functional capacity in frail community elders with cognitive decline: Study protocol for a
randomized multicentre control trial. Trials 2019, 20, 362. [CrossRef]
12. Janssens, J.P.; Pache, J.C.; Nicod, L.P. Physiological changes in respiratory function associated with ageing. Eur. Respir. J. 1999,
13, 197–205. [CrossRef]
13. Petrella, M.; Aprahamian, I.; Mamoni, R.L.; de Vasconcellos Romanini, C.F.; Lima, N.A.; de Cassio Robello, E.; da Costa, D.L.;
An, V.N.; Aguirre, B.N.; Galdeano, J.R.; et al. The effect of a multicomponent exercise protocol (VIVIFRAIL(c)) on inflammatory
profile and physical performance of older adults with different frailty status: Study protocol for a randomized controlled trial.
BMC Geriatr. 2021, 21, 83. [CrossRef] [PubMed]
14. World Health Organization. WHO Guidelines on Physical Activity and Sedentary Behaviour: Web Annex: Evidence Profiles; World
Health Organization: Geneva, Switzerland, 2020.
15. Izquierdo, M.; Merchant, R.A.; Morley, J.E.; Anker, S.D.; Aprahamian, I.; Arai, H.; Aubertin-Leheudre, M.; Bernabei, R.; Cadore,
E.L.; Cesari, M.; et al. International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines. J. Nutr.
Health Aging 2021, 25, 824–853. [CrossRef] [PubMed]
16. Billat, L.V. Interval training for performance: A scientific and empirical practice. Special recommendations for middle- and
long-distance running. Part II: Anaerobic interval training. Sports Med. 2001, 31, 75–90. [CrossRef]
17. Billat, L.V. Interval training for performance: A scientific and empirical practice. Special recommendations for middle- and
long-distance running. Part I: Aerobic interval training. Sports Med. 2001, 31, 13–31. [CrossRef] [PubMed]
18. Laursen, P.B.; Jenkins, D.G. The scientific basis for high-intensity interval training: Optimising training programmes and
maximising performance in highly trained endurance athletes. Sports Med. 2002, 32, 53–73. [CrossRef]
19. Buchheit, M.; Laursen, P.B. High-intensity interval training, solutions to the programming puzzle: Part II: Anaerobic energy,
neuromuscular load and practical applications. Sports Med. 2013, 43, 927–954. [CrossRef]
20. Buchheit, M.; Laursen, P.B. High-intensity interval training, solutions to the programming puzzle: Part I: Cardiopulmonary
emphasis. Sports Med. 2013, 43, 313–338. [CrossRef]
21. Rohmansyah, N.A.; Ka Praja, R.; Phanpheng, Y.; Hiruntrakul, A. High-Intensity Interval Training Versus Moderate-Intensity
Continuous Training for Improving Physical Health in Elderly Women. Inquiry 2023, 60, 469580231172870. [CrossRef]
22. Roxburgh, B.H.; Nolan, P.B.; Weatherwax, R.M.; Dalleck, L.C. Is moderate intensity exercise training combined with high intensity
interval training more effective at improving cardiorespiratory fitness than moderate intensity exercise training alone? J. Sports
Sci. Med. 2014, 13, 702.
23. Kessler, H.S.; Sisson, S.B.; Short, K.R. The potential for high-intensity interval training to reduce cardiometabolic disease risk.
Sports Med. 2012, 42, 489–509. [CrossRef]
24. Alvarez, C.; Ramirez-Campillo, R.; Martinez-Salazar, C.; Mancilla, R.; Flores-Opazo, M.; Cano-Montoya, J.; Ciolac, E.G. Low-
Volume High-Intensity Interval Training as a Therapy for Type 2 Diabetes. Int. J. Sports Med. 2016, 37, 723–729. [CrossRef]
[PubMed]
25. Tjønna, A.E.; Lee, S.J.; Rognmo, Ø.; Stølen, T.O.; Bye, A.; Haram, P.M.; Loennechen, J.P.l.; Al-Share, Q.Y.; Skogvoll, E.; Slørdahl,
S.A. Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome: A pilot study.
Circulation 2008, 118, 346–354. [CrossRef] [PubMed]
26. Cadore, E.L.; Saez de Asteasu, M.L.; Izquierdo, M. Multicomponent exercise and the hallmarks of frailty: Considerations on
cognitive impairment and acute hospitalization. Exp. Gerontol. 2019, 122, 10–14. [CrossRef] [PubMed]
27. Hosseinzadeh, K. High Intensity Interval Training in Elderly Could Improve Elderly Health Significantly. Int. J. Aging Health Mov.
2019, 1, 10–11.
28. Older, P.; Hall, A. The role of cardiopulmonary exercise testing for preoperative evaluation of the elderly. Mortality 1996, 11, 10.
29. West, M.; Jack, S.; Grocott, M. Perioperative cardiopulmonary exercise testing in the elderly. Best Pract. Res. Clin. Anaesthesiol.
2011, 25, 427–437. [CrossRef]
30. Izquierdo, M. Multicomponent physical exercise program: Vivifrail. Nutr. Hosp. 2019, 36, 50–56. [CrossRef]
31. Lambert, C.P.; Evans, W.J. Adaptations to aerobic and resistance exercise in the elderly. Rev. Endocr. Metab. Disord. 2005,
6, 137–143. [CrossRef]
Sports 2023, 11, 219 15 of 16

32. Gonzales, T.I.; Westgate, K.; Strain, T.; Hollidge, S.; Jeon, J.; Christensen, D.L.; Jensen, J.; Wareham, N.J.; Brage, S. Cardiorespiratory
fitness assessment using risk-stratified exercise testing and dose–response relationships with disease outcomes. Sci. Rep. 2021,
11, 15315. [CrossRef]
33. Sietsema, K.E.; Stringer, W.W.; Sue, D.Y.; Ward, S. Wasserman & Whipp’s Principles of Exercise Testing and Interpretation, 6th ed.;
Lippincott Williams & Wilkins (LWW): Philadelphia, PA, USA, 2020.
34. Ross, R.; Blair, S.N.; Arena, R.; Church, T.S.; Després, J.-P.; Franklin, B.A.; Haskell, W.L.; Kaminsky, L.A.; Levine, B.D.; Lavie,
C.J.; et al. Importance of Assessing Cardiorespiratory Fitness in Clinical Practice: A Case for Fitness as a Clinical Vital Sign: A
Scientific Statement from the American Heart Association. Circulation 2016, 134, e653–e699. [CrossRef]
35. Arena, R.; Myers, J.; Abella, J.; Peberdy, M.A.; Bensimhon, D.; Chase, P.; Guazzi, M. Development of a ventilatory classification
system in patients with heart failure. Circulation 2007, 115, 2410–2417. [CrossRef] [PubMed]
36. Guazzi, M.; Arena, R.; Halle, M.; Piepoli, M.F.; Myers, J.; Lavie, C.J. 2016 focused update: Clinical recommendations for
cardiopulmonary exercise testing data assessment in specific patient populations. Eur. Heart J. 2018, 39, 1144–1161. [CrossRef]
[PubMed]
37. Gitt, A.K.; Wasserman, K.; Kilkowski, C.; Kleemann, T.; Kilkowski, A.; Bangert, M.; Schneider, S.; Schwarz, A.; Senges, J. Exercise
anaerobic threshold and ventilatory efficiency identify heart failure patients for high risk of early death. Circulation 2002, 106,
3079–3084. [CrossRef] [PubMed]
38. Coeckelberghs, E.; Buys, R.; Goetschalckx, K.; Cornelissen, V.A.; Vanhees, L. Prognostic value of the oxygen uptake efficiency
slope and other exercise variables in patients with coronary artery disease. Eur. J. Prev. Cardiol. 2016, 23, 237–244. [CrossRef]
[PubMed]
39. Ramos, P.S.; Araújo, C.G.S. Cardiorespiratory optimal point during exercise testing as a predictor of all-cause mortality. Rev. Port.
De Cardiol. 2017, 36, 261–269. [CrossRef]
40. Dias Ferreira Reis, J.; Goncalves, A.; Bras, P.; Ferreira, V.; Viegas, J.; Rio, P.; Moreira, R.; Pereira Silva, T.; Timoteo, A.; Soares, R.
Prognostic value of the cardiorespiratory optimal point during submaximal exercise testing. Eur. Heart J. 2020, 41, ehaa946.0957.
[CrossRef]
41. Baba, R.; Tsuyuki, K.; Yano, H.; Ninomiya, K.; Ebine, K. Robustness of the oxygen uptake efficiency slope to exercise intensity in
patients with coronary artery disease. Nagoya J. Med. Sci. 2010, 72, 83–89.
42. Barros, C.R.; Monte-Silva, K.; Sales, C.B.; Souza, R.P.; Santos, T.; Pessoa, M.; Viana, R.; Alcoforado, L.; Lima, A.M.J.; Fernandes,
J.; et al. Oxygen uptake efficiency slope: A submaximal test evaluation tool that provides cardiopulmonary reserve data in
individuals with Parkinson’s disease. Braz. J. Phys. Ther. 2021, 25, 641–647. [CrossRef]
43. Silva, M.; Baptista, L.; Neves, R.; França, E.; Loureiro, H.; Rezende, M.; Ferreira, V.; Veríssimo, M.; Martins, R. High intensity
interval training improves health-related quality of life in adults and older adults with diagnosed cardiovascular risk. J. Phys.
Educ. Sport 2019, 19, 611–618.
44. Ramírez-Vélez, R.; García-Alonso, N.; Legarra-Gorgoñón, G.; Oscoz-Ochandorena, S.; Oteiza, J.; Izquierdo, M. Ventilatory
efficiency in response to maximal exercise in persistent COVID-19 syndrome patients: A cross-sectional study. Rev. Esp. Cardiol.
2023, 76, 206–209. [CrossRef]
45. Rudd, A.; Khan, H.; Gamble, D.; Stephen, P.; Horgan, G.; Dawson, A.; Frenneaux, M.; Dawson, D.K. 76 Oxygen uptake efficiency
slope—A valuable substitute for peak vo2 ? Heart 2022, 108, A56–A57. [CrossRef]
46. Laukkanen, J.A.; Kunutsor, S.K.; Yates, T.; Willeit, P.; Kujala, U.M.; Khan, H.; Zaccardi, F. Prognostic relevance of cardiorespiratory
fitness as assessed by submaximal exercise testing for all-cause mortality: A UK Biobank prospective study. Mayo Clin. Proc. 2020,
95, 867–878. [CrossRef] [PubMed]
47. Reed, J.L.; Cotie, L.M.; Cole, C.A.; Harris, J.; Moran, B.; Scott, K.; Terada, T.; Buckley, J.P.; Pipe, A.L. Submaximal Exercise Testing
in Cardiovascular Rehabilitation Settings (BEST Study). Front. Physiol. 2019, 10, 1517. [CrossRef]
48. David, R.; Bassett, J. Scientific contributions of A. V. Hill: Exercise physiology pioneer. J. Appl. Physiol. 2002, 93, 1567–1582.
[CrossRef]
49. Meyer, T.; Lucia, A.; Earnest, C.P.; Kindermann, W. A conceptual framework for performance diagnosis and training prescription
from submaximal gas exchange parameters--theory and application. Int. J. Sports Med. 2005, 26 (Suppl. S1), S38–S48. [CrossRef]
[PubMed]
50. Issurin, V.B. New horizons for the methodology and physiology of training periodization. Sports Med. 2010, 40, 189–206.
[CrossRef] [PubMed]
51. Araújo, B.T.S.; Barros, A.; Nunes, D.T.X.; Remígio de Aguiar, M.I.; Mastroianni, V.W.; de Souza, J.A.F.; Fernades, J.; Campos, S.L.;
Brandão, D.C.; Dornelas de Andrade, A. Effects of continuous aerobic training associated with resistance training on maximal
and submaximal exercise tolerance, fatigue, and quality of life of patients post-COVID-19. Physiother. Res. Int. 2023, 28, e1972.
[CrossRef] [PubMed]
52. Guazzi, M.; Agostoni, P.G. Monitoring gas exchange during a constant work rate exercise in patients with left ventricular
dysfunction treated with carvedilol. Am. J. Cardiol. 2000, 85, 660–664. [CrossRef]
53. Malhotra, R.; Bakken, K.; D’Elia, E.; Lewis, G.D. Cardiopulmonary Exercise Testing in Heart Failure. JACC Heart Fail. 2016,
4, 607–616. [CrossRef]
54. Noonan, V.; Dean, E. Submaximal Exercise Testing: Clinical Application and Interpretation. Phys. Ther. 2000, 80, 782–807.
[CrossRef]
Sports 2023, 11, 219 16 of 16

55. Sloth, M.; Sloth, D.; Overgaard, K.; Dalgas, U. Effects of sprint interval training on VO2 max and aerobic exercise performance: A
systematic review and meta-analysis. Scand. J. Med. Sci. Sports 2013, 23, e341–e352. [CrossRef] [PubMed]
56. Francis, D.P.; Shamim, W.; Davies, L.C.; Piepoli, M.F.; Ponikowski, P.; Anker, S.D.; Coats, A.J.S. Cardiopulmonary exercise testing
for prognosis in chronic heart failure: Continuous and independent prognostic value from VE/VCO2 slope and peak VO2 . Eur.
Heart J. 2000, 21, 154–161. [CrossRef] [PubMed]
57. McGurk, S.P.; Blanksby, B.A.; Anderson, M.J. The relationship of hypercapnic ventilatory responses to age, gender and athleticism.
Sports Med. 1995, 19, 173–183. [CrossRef]
58. Moore, B.; Brubaker, P.H.; Stewart, K.P.; Kitzman, D.W. VE/VCO2 slope in older heart failure patients with normal versus reduced
ejection fraction compared with age-matched healthy controls. J. Card. Fail. 2007, 13, 259–262. [CrossRef] [PubMed]
59. Louras, P.; Kamil-Rosenberg, S.; Myers, J.; Fairchild, J.K. Validation of the VE/VCO2 Slope as a Marker of Cognitive Performance
in Older Adults. Arch. Phys. Med. Rehabil. 2022, 103, e158. [CrossRef]
60. Lai, P.; Xue, J.-H.; Xie, M.-J.; Ye, J.-H.; Yang, N.; Zhong, Y.-M.; Liao, Y.-L. High-intensity and moderate-intensity interval training
in heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials. Medicine 2023, 102, e33010.
[CrossRef]
61. Donelli da Silveira, A.; Beust de Lima, J.; da Silva Piardi, D.; dos Santos Macedo, D.; Zanini, M.; Nery, R.; Laukkanen, J.A.; Stein,
R. High-intensity interval training is effective and superior to moderate continuous training in patients with heart failure with
preserved ejection fraction: A randomized clinical trial. Eur. J. Prev. Cardiol. 2020, 27, 1733–1743. [CrossRef]
62. Mueller, S.; Winzer, E.B.; Duvinage, A.; Gevaert, A.B.; Edelmann, F.; Haller, B.; Pieske-Kraigher, E.; Beckers, P.; Bobenko, A.;
Hommel, J. Effect of high-intensity interval training, moderate continuous training, or guideline-based physical activity advice
on peak oxygen consumption in patients with heart failure with preserved ejection fraction: A randomized clinical trial. JAMA
2021, 325, 542–551. [CrossRef]
63. Chou, C.-H.; Fu, T.-C.; Tsai, H.-H.; Hsu, C.-C.; Wang, C.-H.; Wang, J.-S. High-intensity interval training enhances mitochondrial
bioenergetics of platelets in patients with heart failure. Int. J. Cardiol. 2019, 274, 214–220. [CrossRef]
64. Palermo, P.; Mapelli, M.; Campodonico, J.; Vignati, C.; Agostoni, P. P310 Cardiopulmonary Exercise Test in the Evaluation of a
patient with Hfref: The Importance in the Analysis of Gas Kinetics. Eur. Heart J. Suppl. 2023, 25, D163–D164. [CrossRef]
65. Oliveira, R.B.; Myers, J.; Araújo, C.G.; Abella, J.; Mandic, S.; Froelicher, V. Maximal exercise oxygen pulse as a predictor of
mortality among male veterans referred for exercise testing. Eur. J. Cardiovasc. Prev. Rehabil. 2009, 26, 358–364. [CrossRef]
66. Belardinelli, R.; Lacalaprice, F.; Carle, F.; Minnucci, A.; Cianci, G.; Perna, G.; D’Eusanio, G. Exercise-induced myocardial ischaemia
detected by cardiopulmonary exercise testing. Eur. Heart J. 2003, 24, 1304–1313. [CrossRef] [PubMed]
67. Munhoz, E.C.; Hollanda, R.; Vargas, J.P.; Silveira, C.W.; Lemos, A.L.; Hollanda, R.; Ribeiro, J.P. Flattening of oxygen pulse during
exercise may detect extensive myocardial ischemia. Med. Sci. Sports Exerc. 2007, 39, 1221–1226. [CrossRef] [PubMed]
68. De Lorenzo, A.; da Silva, C.L.; Souza, F.C.C.; Serra, S.; Marino, P.; Sl Lima, R. Clinical, scintigraphic, and angiographic predictors
of oxygen pulse abnormality in patients undergoing cardiopulmonary exercise testing. Clin. Cardiol. 2017, 40, 914–918. [CrossRef]
[PubMed]
69. Ramos, P.S.; Ricardo, D.R.; Araujo, C.G. Cardiorespiratory optimal point: A submaximal variable of the cardiopulmonary exercise
testing. Arq. Bras. Cardiol. 2012, 99, 988–996. [CrossRef] [PubMed]
70. Du, L.; Zhang, X.; Chen, K.; Ren, X.; Chen, S.; He, Q. Effect of high-intensity interval training on physical health in coronary
artery disease patients: A meta-analysis of randomized controlled trials. J. Cardiovasc. Dev. Dis. 2021, 8, 158. [CrossRef]
71. Pattyn, N.; Coeckelberghs, E.; Buys, R.; Cornelissen, V.A.; Vanhees, L. Aerobic interval training vs. moderate continuous training
in coronary artery disease patients: A systematic review and meta-analysis. Sports Med. 2014, 44, 687–700. [CrossRef]
72. Xie, B.; Yan, X.; Cai, X.; Li, J. Effects of High-Intensity Interval Training on Aerobic Capacity in Cardiac Patients: A Systematic
Review with Meta-Analysis. BioMed Res. Int. 2017, 2017, 5420840. [CrossRef]
73. Blackwell, J.E.M.; Gharahdaghi, N.; Brook, M.S.; Watanabe, S.; Boereboom, C.L.; Doleman, B.; Lund, J.N.; Wilkinson, D.J.; Smith,
K.; Atherton, P.J.; et al. The physiological impact of high-intensity interval training in octogenarians with comorbidities. J.
Cachexia Sarcopenia Muscle 2021, 12, 866–879. [CrossRef]
74. Laukkanen, J.A.; Zaccardi, F.; Khan, H.; Kurl, S.; Rauramaa, R. Abstract 19920: Long-term Change in Cardiorespiratory Fitness
and All-cause Mortality: A Follow-up Study. Circulation 2015, 132, A19920. [CrossRef]
75. Boereboom, C.L.; Phillips, B.E.; Williams, J.P.; Lund, J.N. A 31-day time to surgery compliant exercise training programme
improves aerobic health in the elderly. Tech. Coloproctol. 2016, 20, 375–382. [CrossRef] [PubMed]
76. Lee, D.-c.; Sui, X.; Artero, E.G.; Lee, I.-M.; Church, T.S.; McAuley, P.A.; Stanford, F.C.; Kohl, H.W.; Blair, S.N. Long-Term Effects
of Changes in Cardiorespiratory Fitness and Body Mass Index on All-Cause and Cardiovascular Disease Mortality in Men.
Circulation 2011, 124, 2483–2490. [CrossRef] [PubMed]

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual
author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to
people or property resulting from any ideas, methods, instructions or products referred to in the content.