Cardiac RehabilitationEXCARMANCT07288840

Exercise Prescription in Cardiac Rehabilitation Mediated by Autonomic Function

An observational study of Cardiac Rehabilitation and Exercise Therapy, run by Instituto Politécnico de Leiria at 2 sites in Portugal.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Cardiac Rehabilitation, Exercise Therapy, Autonomic Nervous System Imbalance
How many people: 90 participants
Where: 2 sitesPortugal
Study dates: 2 Jan 2024to 31 Dec 2026
Phase: Observational
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Study population: Adult patients diagnosed with non-ischemic heart failure with reduced ejection fraction (NIHFrEF) or stable coronary artery disease without heart failure (CADnonHF), consecutively enrolled in the Cardiac Rehabilitation Program at Centro Hospitalar de Leiria, and undergoing comprehensive autonomic and metabolic assessment."

Who may be able to join

Patients with Coronary artery disease and no heart failure criteria
Patients with non ischaemic heart failure and reduced left ventricle ejection fraction

Who cannot join

patients with ongoing acute coronary syndrome
patients with ongoing acute decompensated heart failure
Severe valvular heart disease that might confound the relationship between exercise and autonomic function.
Severe arrhythmias (e.g., sustained ventricular tachycardia, atrial fibrillation with a rapid ventricular rate) that are symptomatic or untreated
Severe uncontrolled hypertension (e.g., systolic BP > 180 mmHg or diastolic BP > 110 mmHg)
Active infectious diseases or other significant acute medical illnesses (e.g., sepsis, active malignancy, acute kidney injury)

Show all 24Show fewer

Pregnancy or lactation (to ensure safety during exercise interventions)
Significant cognitive impairment or mental illness (e.g., dementia, schizophrenia) that would impair the ability to follow exercise protocols or understand study instructions
nability to comply with study procedures due to any reason (e.g., language barriers, lack of informed consent)
Chronically immunocompromised states (e.g., HIV with CD4 count < 200 cells/µL or on immunosuppressive therapy)
Presence of significant comorbidities such as advanced chronic obstructive pulmonary disease (COPD), kidney disease (e.g., stage 4-5 chronic kidney disease), or uncontrolled diabetes that would make exercise unsafe or confound the study outcomes
Critical limb ischemia, or severely symptomatic peripheral artery disease or claudication limiting functional capacity and response to exercise
Advanced chronic kidney disease (stage 4 or 5), due to contraindications with exercise
Severe anemia (hemoglobin < 8 g/dL) or other blood disorders that affect exercise capacity
Inability to tolerate exercise due to other comorbidities or debility
individuals with known autonomic neuropathy (such as poorly controlled diabetes or neurodegenerative disorders)
Specific Exclusion Criteria for Coronary Artery Disease (CAD) without Heart Failure Group:
Left ventricular ejection fraction (LVEF) < 50%
Clinical/echocardiographic criteria of heart failure with oreserved ejection fraction.
Specific Exclusion Criteria for Non-Ischemic Heart Failure with Reduced LVEF Group:
Ischemic heart disease or previous myocardial infarction
LVEF > 40%
End-stage heart failure (e.g., patients on a heart transplant list, those with imminent need for mechanical circulatory support like LVAD).
Severe fluid overload that cannot be corrected

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Portugal2 sites

ICVS - Life and Health Sciences Research Institute, Minho University Medical School
Braga, Minho, 4710-057
ciTechCare - Center for Innovative Care and Health Technology
Leiria, Leiria District, 2414-016

Other trials in Portugal

About this study

Cardiac rehabilitation (CR) is an essential secondary prevention component in the treatment of cardiovascular diseases and one of the most cost- effective clinical interventions. Exercise training (ET) in CR programs (CRP) has unequivocal benefits in the reduction of cardiovascular adverse events, by decreasing the overactivated sympathetic tone. This ET added value can be measured by variables that express autonomic control using indirect (standard) or direct (experimental) methodologies. Direct autonomic assessment (ex. Microneurography) is accurate but unusable in daily practice, whereas standard indirect autonomic assessment using clinical parameters is imprecise, resulting in underprescription to safeguard patient safety, with less benefit to the patients. In this project, we aim to apply Machine Learning models to a set of indirect and direct variables, to make a multivariate correlation analysis and so define a normalization factor for exercise prescription.

Read the detailed description

Cardiac rehabilitation (CR) has proved to be an essential secondary prevention component of the continuum in the treatment of Cardiovascular diseases (CVD), being a Class I recommendation with level of evidence A and B on the European Society of Cardiology (ESC) and American Heart Association and American College of Cardiology (AHA/ACC) Guidelines. CR is also one of the most cost-effective clinical interventions in the treatment of CVD. These diseases, namely coronary artery disease (CAD) and heart failure (HF), are associated with autonomic dysfunction, particularly an overactivation of the autonomic sympathetic system (ASS), leading to coronary vasoconstriction, myocardial remodeling, and increased basal oxygen consumption. The main component of the CR programs (CRP) is Exercise training (ET), one of the central pillars of non- pharmacological treatment in CVD, thus preventing the above- mentioned progression of deleterious effects. The role of ET in CRP has been increasingly emphasized; however, it is still not clear, among the variety of existing training programs, which is the optimal combination and type of exercise (aerobic/anaerobic or both), frequency and duration of the sessions, whose prescription should be customized considering the patient's clinical history and the pre-CRP exam results. This limitation is pointed out as a major drawback in obtaining optimized results on CRP. The absence of a methodology that can more precisely assess and hence better quantify the effect of the prescription, safely optimizing the training plan, is one of the central problems regarding CR, and will be addressed in this research proposal putting the autonomic modulation of CV system in the center of the rational to prescribe ET in CRP. The main objective of this research plan is to draw an objective and individualized protocol to prescribe ET in CRPs based on the Autonomic output.

After careful ponderation, two important but different pathologies with clearly demonstrated ASS overactivation were considered: "non- ischemic HF with reduced ejection fraction" (NIHFrEF) and "CAD without HF" (CADnonHF). The following secondary objectives contribute to the achievement of this central goal, and define the majority of the associated tasks:

Evaluation of the basal sympathetic activation pattern in patients with NIHFrEF and CADnonHF (Task2);
Definition of a normalization factor regarding sympathetic activation for ET prescription purposes in the context of CRPs (Task3)
Definition of an exercise training program for CRPs with prescription guided by the autonomic response (Task 4); In Task 2 the basal activation level of the Autonomic nervous system (ANS) will be characterized for each of the two identified conditions (NIHFrEF and CADnonHF) using a sample of 30 patients for each one to ensure a good approximation of the sampling distribution of the mean using the central limit theorem, and the participants will be enrolled at the CR consultation in Centro Hospitalar de Leiria (CHL) Cardiology department. The CHL CR Unit is accreditated by the European Association of Preventive Cardiology (EAPC) since 2022. Classical indirect measures of ANS which are relatively imprecise, such as heart rate variability (HRV) and derived indexes will be obtained with a 24h Holter and a "long duration EKG", as well as the first minute HR recovery with a Cardiopulmonary Exercise Test (CPET) and also serum catecholamines in blood and urine samples. Besides these indirect measures, a direct recording of the SNS obtained by microneurography (MSNA) will be conducted, being available at the host research institution (ciTechCare). The set of variables (autonomic and its derivatives), together with the metabolic biomarkers, will allow a multivariate correlation analysis followed by the use of the Machine Learning algorithm "Principal Component analysis" (PCA) to reduce the dimensionality of the data set, and so define a normalization factor for exercise prescription purposes, which corresponds to the main goal associated with Task 3. This normalization factor will be key to establish the individual pattern of sympathetic activation, establishing the same starting point for initial prescription of exercise and an unbiased follow up of patient's performance. Regarding Task 4, training plans (aerobic/anaerobic load) will be carried out in conjunction with the levels defined for the classification model (one of the derivable of the previous Task), and will be developed by the candidate along with the Physiatrist of the CRP Team, by setting a combined (aerobic and resistance) and stratified (with various levels of intensity, frequency, stages and duration) training program. This protocol will be evaluated by the due health ethics committees (Task 1), and all legal issues regarding safety and data protection will be respected.

Regarding risks and strategies to mitigate them, the main risk is related to data assessment. In that case other hospitals may be contacted to increase the number of participants. Another risk is related to task dependency. In this case, the experience of the mentors and the integration of this project in a team with expertise in CRP and familiar with artificial intelligence applications in Medicine will be determinant.

Conditions: Cardiac Rehabilitation, Exercise Therapy, Autonomic Nervous System Imbalance, Treatment Outcomes
Keywords: Cardiac Rehabilitation, Exercise prescription, Autonomic funtion, microneurography, cardiopulmonary exercise testing

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT07288840
Study group	Role	What they receive
Patients with Coronary artery disease without Heart Failure (CADnonHF)		This group with clearly demonstrated Autonomic Simpathetic System overactivation will have a detailed evaluation of the autonomic nervous system by performing an echocardiogram, 24-hour Holter monitoring, cardiopulmonary exercise test, long-term electrocardiogram, microneurography, and serum and urinary determination of catecholamine levels
Patients with non- ischemic Heart Failure with reduced ejection fraction (NIHFrEF)		This group, that also has clearly demonstrated Autonomic Simpathetic System overactivation, will, in the same way, have a detailed evaluation of the autonomic nervous system by performing an echocardiogram, 24-hour Holter monitoring, cardiopulmonary exercise test, long-term electrocardiogram, microneurography, and serum and urinary determination of catecholamine levels

What is being measured

The primary outcome is the main question the study is designed to answer.

Normalization Factor for Sympathetic Activation Derived from Multimodal Autonomic Assessment
A composite autonomic normalization factor will be generated using Principal Component Analysis (PCA) applied to multimodal autonomic and metabolic biomarkers (including microneurography-derived MSNA, heart rate variability indices from 24-hour Holter, CPET first-minute heart rate recovery, and serum/urinary catecholamines). This factor will quantify the individual degree of sympathetic activation and will serve as the basis for personalized exercise training prescription (Units of mesaure: unitless)
Measured: Baseline (before initiation of cardiac rehabilitation program)

Secondary outcomes (12)

Basal Sympathetic Nervous System Activity (MSNA burst frequency)
Direct sympathetic activity will be quantified using microneurography (sympathetic nerve activity, MSNA), expressed as bursts/minute (bursts/min), to characterize autonomic dysfunction in NIHFrEF and CADnonHF groups.
Measured: Baseline
SDNN (Heart Rate Variability) obtained from 24-hour Holter ECG and long-duration ECG
Standard deviation of normal-to-normal intervals as an index of overall HRV (Unit of Measure: milliseconds - ms)
Measured: Baseline
RMSSD (Heart Rate Variability) obtained from 24-hour Holter ECG and long duration ECG
Root mean square of successive differences as a measure of parasympathetic activity (Unit of Measure: ms²)
Measured: Baseline
LF Power (Heart Rate Variability) Low-frequency spectral power obtained from 24-hour Holter ECG
LF component of HRV as an index of sympathetic/parasympathetic modulation (Units ms²)
Measured: Baseline
LF/HF Ratio (Heart Rate Variability) obtained from 24-hour Holter ECG
Ratio of low-frequency to high-frequency power reflecting autonomic balance (Unit of Measure: unitless)
Measured: Baseline
Plasma epinephrine concentration
Quantified by blood sample to assess biochemical sympathetic activity. Unit of Measure: pg/mL
Measured: Baseline
Plasma norepinephrine concentration
Quantified by blood sample to assess sympathetic activation (Unit of Measure: pg/mL)
Measured: Baseline
Plasma dopamine concentration
Quantified by blood sample to assess catecholaminergic activity (units of measure pg/mL)
Measured: Baseline
Urinary metanephrine
24-hour urinary excretion as an index of catecholamine metabolism (unit of measure µg/24h)
Measured: Baseline
Urinary normetanephrine
24-hour urinary excretion measurement (unit of measure: µg/24h)
Measured: Baseline
Urinary 3-methoxytyramine
24-hour urinary excretion measurement (unit of measure - µg/24h)
Measured: Baseline
CPET First-Minute Heart Rate Recovery
Difference between peak HR and HR at 1-minute post-exercise during cardiopulmonary exercise test, reflecting parasympathetic reactivation (units of measure: beats per minute)
Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

2 Jan 202431 Dec 2026

First posted17 Dec 2025
Study start2 Jan 2024
Primary completionDec 2025 (estimated)
Study completion31 Dec 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (13)Papers the sponsor has linked to this study.
Other trials for Cardiac RehabilitationStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Case only
Time perspective: Prospective
Enrolment: 90 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07288840
Sponsor's protocol ID: FCT 2024.04320.BD
Acronym: EXCARMA
Status last verified: Dec 2025
First submitted: 24 Nov 2025
Last updated: 17 Dec 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: Individual participant data will not be shared because the study collects sensitive physiological and clinical information that carries a high risk of re-identification, and current institutional and regulatory constraints do not permit external data sharing.

Publications

Anderson L, Thompson DR, Oldridge N, Zwisler AD, Rees K, Martin N, Taylor RS. Exercise-based cardiac rehabilitation for coronary heart disease. Cochrane Database Syst Rev. 2016 Jan 5;2016(1):CD001800. doi: 10.1002/14651858.CD001800.pub3.
PubMed 26730878
Watson AM, Hood SG, May CN. Mechanisms of sympathetic activation in heart failure. Clin Exp Pharmacol Physiol. 2006 Dec;33(12):1269-74. doi: 10.1111/j.1440-1681.2006.04523.x.
PubMed 17184514
Townsend N, Wilson L, Bhatnagar P, Wickramasinghe K, Rayner M, Nichols M. Cardiovascular disease in Europe: epidemiological update 2016. Eur Heart J. 2016 Nov 7;37(42):3232-3245. doi: 10.1093/eurheartj/ehw334. Epub 2016 Aug 14. No abstract available.
PubMed 27523477
Bento L, Fonseca-Pinto R, Povoa P. Autonomic nervous system monitoring in intensive care as a prognostic tool. Systematic review. Rev Bras Ter Intensiva. 2017 Oct-Dec;29(4):481-489. doi: 10.5935/0103-507X.20170072.
PubMed 29340538
Sacramento JF, Ribeiro MJ, Rodrigues T, Olea E, Melo BF, Guarino MP, Fonseca-Pinto R, Ferreira CR, Coelho J, Obeso A, Seica R, Matafome P, Conde SV. Functional abolition of carotid body activity restores insulin action and glucose homeostasis in rats: key roles for visceral adipose tissue and the liver. Diabetologia. 2017 Jan;60(1):158-168. doi: 10.1007/s00125-016-4133-y. Epub 2016 Oct 16.
PubMed 27744526
Sandesara PB, Lambert CT, Gordon NF, Fletcher GF, Franklin BA, Wenger NK, Sperling L. Cardiac rehabilitation and risk reduction: time to "rebrand and reinvigorate". J Am Coll Cardiol. 2015 Feb 3;65(4):389-395. doi: 10.1016/j.jacc.2014.10.059.
PubMed 25634839
Adler AJ, Martin N, Mariani J, Tajer CD, Owolabi OO, Free C, Serrano NC, Casas JP, Perel P. Mobile phone text messaging to improve medication adherence in secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2017 Apr 29;4(4):CD011851. doi: 10.1002/14651858.CD011851.pub2.
PubMed 28455948
Besnier F, Labrunee M, Pathak A, Pavy-Le Traon A, Gales C, Senard JM, Guiraud T. Exercise training-induced modification in autonomic nervous system: An update for cardiac patients. Ann Phys Rehabil Med. 2017 Jan;60(1):27-35. doi: 10.1016/j.rehab.2016.07.002. Epub 2016 Aug 16.
PubMed 27542313
Long L, Anderson L, He J, Gandhi M, Dewhirst A, Bridges C, Taylor R. Exercise-based cardiac rehabilitation for stable angina: systematic review and meta-analysis. Open Heart. 2019 Jun 5;6(1):e000989. doi: 10.1136/openhrt-2018-000989. eCollection 2019.
PubMed 31245012
Alter DA, Zagorski B, Marzolini S, Forhan M, Oh PI. On-site programmatic attendance to cardiac rehabilitation and the healthy-adherer effect. Eur J Prev Cardiol. 2015 Oct;22(10):1232-46. doi: 10.1177/2047487314544084. Epub 2014 Jul 30.
PubMed 25079239
Andrade N, Alves E, Costa AR, Moura-Ferreira P, Azevedo A, Lunet N. Knowledge about cardiovascular disease in Portugal. Rev Port Cardiol (Engl Ed). 2018 Aug;37(8):669-677. doi: 10.1016/j.repc.2017.10.017. Epub 2018 Jul 25. English, Portuguese.
PubMed 30055948
Abreu A, Mendes M, Dores H, Silveira C, Fontes P, Teixeira M, Santa Clara H, Morais J. Mandatory criteria for cardiac rehabilitation programs: 2018 guidelines from the Portuguese Society of Cardiology. Rev Port Cardiol (Engl Ed). 2018 May;37(5):363-373. doi: 10.1016/j.repc.2018.02.006. Epub 2018 Apr 30. English, Portuguese.
PubMed 29724635
Atlas Writing Group; ESC Atlas of Cardiology is a compendium of cardiovascular statistics compiled by the European Heart Agency, a department of the European Society of Cardiology.; Developed in collaboration with the national societies of the European Society of Cardiology member countries; Timmis A, Townsend N, Gale CP, Torbica A, Lettino M, Petersen SE, Mossialos EA, Maggioni AP, Kazakiewicz D, May HT, De Smedt D, Flather M, Zuhlke L, Beltrame JF, Huculeci R, Tavazzi L, Hindricks G, Bax J, Casadei B, Achenbach S, Wright L, Vardas P. European Society of Cardiology: Cardiovascular Disease Statistics 2019 (Executive Summary). Eur Heart J Qual Care Clin Outcomes. 2020 Jan 1;6(1):7-9. doi: 10.1093/ehjqcco/qcz065. No abstract available.
PubMed 31957796

Interested in taking part?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 17 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Exercise Prescription in Cardiac Rehabilitation Mediated by Autonomic Function
ClinicalTrials.gov ID: NCT07288840
Acronym / sponsor ID: EXCARMA / FCT 2024.04320.BD
Conditions: Cardiac Rehabilitation, Exercise Therapy, Autonomic Nervous System Imbalance, Treatment Outcomes
Keywords: Cardiac Rehabilitation, Exercise prescription, Autonomic funtion, microneurography, cardiopulmonary exercise testing
Study type: Observational
Recruitment status: Enrolling by invitation
Enrolment: 90 participants (estimated)
Lead sponsor: Instituto Politécnico de LeiriaUniversity, hospital or other
Collaborators: Universidade do Minho - ICVS, Hospital de Santo André, Fundação para a Ciência e a Tecnologia
Study start: 2 Jan 2024 (actual)
Primary completion: Dec 2025 (estimated)
Study completion: 31 Dec 2026 (estimated)
First posted: 17 Dec 2025 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Evaluation of the basal sympathetic activation pattern in patients with NIHFrEF and CADnonHF (Task2);
Definition of a normalization factor regarding sympathetic activation for ET prescription purposes in the context of CRPs (Task3)
Definition of an exercise training program for CRPs with prescription guided by the autonomic response (Task 4); In Task 2 the basal activation level of the Autonomic nervous system (ANS) will be characterized for each of the two identified conditions (NIHFrEF and CADnonHF) using a sample of 30 patients for each one to ensure a good approximation of the sampling distribution of the mean using the central limit theorem, and the participants will be enrolled at the CR consultation in Centro Hospitalar de Leiria (CHL) Cardiology department. The CHL CR Unit is accreditated by the European Association of Preventive Cardiology (EAPC) since 2022. Classical indirect measures of ANS which are relatively imprecise, such as heart rate variability (HRV) and derived indexes will be obtained with a 24h Holter and a "long duration EKG", as well as the first minute HR recovery with a Cardiopulmonary Exercise Test (CPET) and also serum catecholamines in blood and urine samples. Besides these indirect measures, a direct recording of the SNS obtained by microneurography (MSNA) will be conducted, being available at the host research institution (ciTechCare). The set of variables (autonomic and its derivatives), together with the metabolic biomarkers, will allow a multivariate correlation analysis followed by the use of the Machine Learning algorithm "Principal Component analysis" (PCA) to reduce the dimensionality of the data set, and so define a normalization factor for exercise prescription purposes, which corresponds to the main goal associated with Task 3. This normalization factor will be key to establish the individual pattern of sympathetic activation, establishing the same starting point for initial prescription of exercise and an unbiased follow up of patient's performance. Regarding Task 4, training plans (aerobic/anaerobic load) will be carried out in conjunction with the levels defined for the classification model (one of the derivable of the previous Task), and will be developed by the candidate along with the Physiatrist of the CRP Team, by setting a combined (aerobic and resistance) and stratified (with various levels of intensity, frequency, stages and duration) training program. This protocol will be evaluated by the due health ethics committees (Task 1), and all legal issues regarding safety and data protection will be respected.

Study design

Observational model: Case only
Time perspective: Prospective
Number of arms: 2

Arm	Type	Receives
Patients with Coronary artery disease without Heart Failure (CADnonHF)	–	–This group with clearly demonstrated Autonomic Simpathetic System overactivation will have a detailed evaluation of the autonomic nervous system by performing an echocardiogram, 24-hour Holter monitoring, cardiopulmonary exercise test, long-term electrocardiogram, microneurography, and serum and urinary determination of catecholamine levels
Patients with non- ischemic Heart Failure with reduced ejection fraction (NIHFrEF)	–	–This group, that also has clearly demonstrated Autonomic Simpathetic System overactivation, will, in the same way, have a detailed evaluation of the autonomic nervous system by performing an echocardiogram, 24-hour Holter monitoring, cardiopulmonary exercise test, long-term electrocardiogram, microneurography, and serum and urinary determination of catecholamine levels

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: Adult patients diagnosed with non-ischemic heart failure with reduced ejection fraction (NIHFrEF) or stable coronary artery disease without heart failure (CADnonHF), consecutively enrolled in the Cardiac Rehabilitation Program at Centro Hospitalar de Leiria, and undergoing comprehensive autonomic and metabolic assessment."

Key inclusion criteria (2 listed)

Patients with Coronary artery disease and no heart failure criteria
Patients with non ischaemic heart failure and reduced left ventricle ejection fraction

Key exclusion criteria (24 listed)

patients with ongoing acute coronary syndrome
patients with ongoing acute decompensated heart failure
Severe valvular heart disease that might confound the relationship between exercise and autonomic function.
Severe arrhythmias (e.g., sustained ventricular tachycardia, atrial fibrillation with a rapid ventricular rate) that are symptomatic or untreated
Severe uncontrolled hypertension (e.g., systolic BP > 180 mmHg or diastolic BP > 110 mmHg)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

Normalization Factor for Sympathetic Activation Derived from Multimodal Autonomic Assessment
Time frame: Baseline (before initiation of cardiac rehabilitation program)
A composite autonomic normalization factor will be generated using Principal Component Analysis (PCA) applied to multimodal autonomic and metabolic biomarkers (including microneurography-derived MSNA, heart rate variability indices from 24-hour Holter, CPET first-minute heart rate recovery, and serum/urinary catecholamines). This factor will quantify the individual degree of sympathetic activation and will serve as the basis for personalized exercise training prescription (Units of mesaure: unitless)

12 secondary outcomes

Basal Sympathetic Nervous System Activity (MSNA burst frequency)
Time frame: Baseline
SDNN (Heart Rate Variability) obtained from 24-hour Holter ECG and long-duration ECG
Time frame: Baseline
RMSSD (Heart Rate Variability) obtained from 24-hour Holter ECG and long duration ECG
Time frame: Baseline
LF Power (Heart Rate Variability) Low-frequency spectral power obtained from 24-hour Holter ECG
Time frame: Baseline
LF/HF Ratio (Heart Rate Variability) obtained from 24-hour Holter ECG
Time frame: Baseline
Plasma epinephrine concentration
Time frame: Baseline
Plasma norepinephrine concentration
Time frame: Baseline
Plasma dopamine concentration
Time frame: Baseline
Urinary metanephrine
Time frame: Baseline
Urinary normetanephrine
Time frame: Baseline
Urinary 3-methoxytyramine
Time frame: Baseline
CPET First-Minute Heart Rate Recovery
Time frame: Baseline

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2025.
Background: PubMed 26730878Anderson L, Thompson DR, Oldridge N, Zwisler AD, Rees K, Martin N, Taylor RS. Exercise-based cardiac rehabilitation for coronary heart disease. Cochrane Database Syst Rev. 2016 Jan 5;2016(1):CD001800. doi: 10.1002/14651858.CD001800.pub3.
Background: PubMed 17184514Watson AM, Hood SG, May CN. Mechanisms of sympathetic activation in heart failure. Clin Exp Pharmacol Physiol. 2006 Dec;33(12):1269-74. doi: 10.1111/j.1440-1681.2006.04523.x.
Background: PubMed 27523477Townsend N, Wilson L, Bhatnagar P, Wickramasinghe K, Rayner M, Nichols M. Cardiovascular disease in Europe: epidemiological update 2016. Eur Heart J. 2016 Nov 7;37(42):3232-3245. doi: 10.1093/eurheartj/ehw334. Epub 2016 Aug 14. No abstract available.
Background: PubMed 29340538Bento L, Fonseca-Pinto R, Povoa P. Autonomic nervous system monitoring in intensive care as a prognostic tool. Systematic review. Rev Bras Ter Intensiva. 2017 Oct-Dec;29(4):481-489. doi: 10.5935/0103-507X.20170072.
Background: PubMed 27744526Sacramento JF, Ribeiro MJ, Rodrigues T, Olea E, Melo BF, Guarino MP, Fonseca-Pinto R, Ferreira CR, Coelho J, Obeso A, Seica R, Matafome P, Conde SV. Functional abolition of carotid body activity restores insulin action and glucose homeostasis in rats: key roles for visceral adipose tissue and the liver. Diabetologia. 2017 Jan;60(1):158-168. doi: 10.1007/s00125-016-4133-y. Epub 2016 Oct 16.
Background: PubMed 25634839Sandesara PB, Lambert CT, Gordon NF, Fletcher GF, Franklin BA, Wenger NK, Sperling L. Cardiac rehabilitation and risk reduction: time to "rebrand and reinvigorate". J Am Coll Cardiol. 2015 Feb 3;65(4):389-395. doi: 10.1016/j.jacc.2014.10.059.
Background: PubMed 28455948Adler AJ, Martin N, Mariani J, Tajer CD, Owolabi OO, Free C, Serrano NC, Casas JP, Perel P. Mobile phone text messaging to improve medication adherence in secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2017 Apr 29;4(4):CD011851. doi: 10.1002/14651858.CD011851.pub2.
Background: PubMed 27542313Besnier F, Labrunee M, Pathak A, Pavy-Le Traon A, Gales C, Senard JM, Guiraud T. Exercise training-induced modification in autonomic nervous system: An update for cardiac patients. Ann Phys Rehabil Med. 2017 Jan;60(1):27-35. doi: 10.1016/j.rehab.2016.07.002. Epub 2016 Aug 16.
Background: PubMed 31245012Long L, Anderson L, He J, Gandhi M, Dewhirst A, Bridges C, Taylor R. Exercise-based cardiac rehabilitation for stable angina: systematic review and meta-analysis. Open Heart. 2019 Jun 5;6(1):e000989. doi: 10.1136/openhrt-2018-000989. eCollection 2019.
Background: PubMed 25079239Alter DA, Zagorski B, Marzolini S, Forhan M, Oh PI. On-site programmatic attendance to cardiac rehabilitation and the healthy-adherer effect. Eur J Prev Cardiol. 2015 Oct;22(10):1232-46. doi: 10.1177/2047487314544084. Epub 2014 Jul 30.
Background: PubMed 30055948Andrade N, Alves E, Costa AR, Moura-Ferreira P, Azevedo A, Lunet N. Knowledge about cardiovascular disease in Portugal. Rev Port Cardiol (Engl Ed). 2018 Aug;37(8):669-677. doi: 10.1016/j.repc.2017.10.017. Epub 2018 Jul 25. English, Portuguese.
Background: PubMed 29724635Abreu A, Mendes M, Dores H, Silveira C, Fontes P, Teixeira M, Santa Clara H, Morais J. Mandatory criteria for cardiac rehabilitation programs: 2018 guidelines from the Portuguese Society of Cardiology. Rev Port Cardiol (Engl Ed). 2018 May;37(5):363-373. doi: 10.1016/j.repc.2018.02.006. Epub 2018 Apr 30. English, Portuguese.
Individual participant dataSharing planned: No. Individual participant data will not be shared because the study collects sensitive physiological and clinical information that carries a high risk of re-identification, and current institutional and regulatory constraints do not permit external data sharing.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Vitor Hugo Eira Pereira, MD, PhD study director

ICVS - Life and Health Sciences Research Institute, Minho University Medical School

Rui Manuel Fonseca Pinto, MD, PhD study director

ciTechCare - Center for Innovative Care and Health Technology, Polytechnic University of Leiria

João Carlos Araújo Morais, MD,PhD study director

ciTechCare - Center for Innovative Care and Health Technology

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Cardiac Rehabilitation and Exercise Therapy, run by Instituto Politécnico de Leiria at 2 sites in Portugal.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: enrolling by invitation, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Normalization Factor for Sympathetic Activation Derived from Multimodal Autonomic Assessment (time frame: Baseline (before initiation of cardiac rehabilitation program)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07288840, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2025.