Cardiac Rehabilitation in Patients With Refractory Angina

The purpose of this study is to evaluate the safety and feasibility of cardiovascular rehabilitation in Patients with refractory angina, evaluate the effect of cardiovascular rehabilitation in patients with angina Refractory, by maximal oxygen consumption (VO2max) and global myocardial ischemic load by Stress Echocardiography; To evaluate the presence of myocardial injury, caused by physical stress, through ultra-sensitive troponin after sessions of aerobic physical activity, evaluating the behavior during the training period; To evaluate the effect of rehabilitation on the modulation of sympathetic activity and inflammation, muscular blood flow and lipid metabolism; To evaluate of the effect of rehabilitation on ventricular function through Stress echocardiography; Detection of ischemic episodes and arrhythmias identified during the Rehabilitation sessions through external cardiac monitoring (telemetry); Evaluate the quality of life assessment through the SF-36 questionnaire, Canadian Cardiovascular Society, the number of symptomatic episodes of ischemia, daily sublingual nitrate intake.

Study Overview

• Status: Completed
• Conditions: Refractory Angina
• Intervention / Treatment: Behavioral: Cardiac Rehabilitation

Detailed Description

After signing the informed consent form, patients will be randomized into 4 groups: 1. Optimized clinical treatment group + physical training for 12 weeks (TF); 2. optimized clinical treatment group (CT); 3. Group with coronary insufficiency without angina (CD); Group 4: normal healthy subjects All patients will be submitted to the following procedures in 2 moments * (times 0 and 3): -Routine laboratory tests including study of total cholesterol, LDL-cholesterol, -HDL-cholesterol, including study of the functionality of HDL-c, triglycerides, complete blood count, renal function, fasting glycemia, glycosylated hemoglobin (HbA1C); - Dosage of biomarkers of myocardial ischemia (ultra-sensitive troponin); - Dosage of inflammatory markers: Tumor necrosis factor (TNFn), interleukins 1 and 6 (IL-1 and IL-6), ultra-sensitive C-reactive protein (CRP); - Vascular endothelial growth factor (VEGF) dosage; - ergospirometric test in cycloergometer; - Echocardiogram with physical stress with evaluation of myocardial perfusion and function; - Evaluation of sympathetic activity through microneurography; - Evaluation of vascular reactivity through ultrasound of the brachial artery. - Evaluation of muscular blood flow through plethysmography; - Isometric exercise protocols; - Mental stress protocol - Quality of Life Questionnaire; - Diary of angina. After the initial examinations, the candidates of the TF group will be evaluated by cardiovascular rehabilitation team, for training prescription, which will be performed in a hospital environment, supervised by a qualified doctor. The rehabilitation may be interrupted in any patient, for safety measure, if the investigator deems it appropriate. All patients in both groups will receive clinical follow-up during the protocol, with monthly consultations during the 12-week protocol period (time 0 to 3), in which clinical evaluations of symptoms and quality of life of the patients will be performed . Any clinical intercurrence will be promptly annotated and evaluated according to the need of the moment. After this period, routine outpatient follow-up is scheduled at the outpatient clinic, and counseling for unsupervised physical training, according to the results of the study. All laboratory, clinical, imaging, and functional parameters will be evaluated before and at the end of the protocol.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 05652-000
    • Instituto Israelita de Ensino e Pesquisa Albert Einstein 's (IIEP)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Group 1 and 2

Inclusion Criteria:

• Stable angina functional class II to IV according to the classification of Canadian Cardiovascular Society (CCS) 39, or limiting angina in Perception of the patient;
• Documented myocardial ischemia by imaging method;
• Patients not eligible for myocardial revascularization procedures surgical conventional, due to the unfavorable anatomy;
• Signature of the Free and Informed Consent Form.

Exclusion Criteria:

• Patients with definitive pacemaker or implantable cardioverter defibrillator (ICD);
• Patients with non-sinus heart rhythm;
• Patients with complete intraventricular block;
• Acute coronary syndrome (myocardial infarction or unstable angina) or previous procedures for myocardial revascularization (angioplasty / surgery) less than 3 months;
• Functional impossibility (orthopedic, rheumatic, neurological, or otherwise) or social for participation in the Rehabilitation Program;
• Classification of risk for American Heart Association class D physical training (unstable ischemia, stenosis or severe or symptomatic valve insufficiency, congenital heart disease, decompensated heart failure, uncontrolled arrhythmias and other conditions that may be aggravated by exercise).

Group 3

Inclusion Criteria:

• Patients with coronary insufficiency without angina;
• Signature of the Free and Informed Consent Form.

Group 4

Inclusion Criteria:

• Signature of the Free and Informed Consent Form;
• Healthy;
• Non-smokers;
• Sedentary

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clinical treatment physical training; Patients with optimized clinical treatment group that will do physical training for 12 weeks. They will do the tests in moment 1 and after 3 mounths. The intervention is the Cardiac Rehabilitation.	Behavioral: Cardiac Rehabilitation; The physical training program will start shortly after the initial exams have been completed. The physical training protocol will consist of a 12-week duration, with a frequency of 3 weekly sessions of 60 minutes duration each. The intensity will be prescribed from the echocardiogram with effort and cardiopulmonary test. All sessions will be monitored by telemetry and will be distributed as follows: 5 minutes warm up; 30 to 40 minutes of aerobic exercise (treadmill). The training intensity will be prescribed individually, based on the results of the test results;; 10 minutes of localized exercises;; 5 minutes of relaxation.
No Intervention: Optimized clinical treatment; Patients with optimized clinical treatment group that will not do physical training.They will do the tests in moment 1 and after 3 mounths.
No Intervention: Coronary insufficiency without angina; Group with coronary insufficiency without angina and will not do physical training. They will do the tests only one moment.
No Intervention: Normal healthy subjects; Group normal healthy subjects, without coronary injuries, diabetes, hypertension and another chronic disease. These group have be sedentary and will not do physical training. They will do the tests only one moment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular rehabilitation in patients with refractory angina is safe;	Evaluated number of patients who have any kind of cardiovascular event during rehabilitation, as well as number of sore throat during the sessions.	3 months of rehabilitation
Cardiovascular rehabilitation in patients with refractory angina is efficient;	Evaluated number of sore throat during the sessions.	3 months of rehabilitation
Improve the maximal oxygen consumption	Improvement of Maximal oxygen uptake (VO2max)	3 months of rehabilitation
Improve the global myocardial ischemic load	Reduction of myocardial ischemia, evidenced by improvement of the standard by effort echocardiography	3 months of rehabilitation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of myocardial injury caused by physical stress	Improves levels of Troponin-T after 1 exercise session at the initial moment of the Protocol and after 3 months.	3 months of rehabilitation
Rehabilitation will modulate sympathetic activity	Decreased sympathetic nerve activity measured by the amount of shots in his microneurography	3 months of rehabilitation
Improvement of ventricular function	Improvement of ventricular function through stress echocardiography in patients undergoing rehabilitation	3 months of rehabilitation
Improvement of the quality of life	Improvement of the quality of life measured through the SF-36 questionnaire.	3 months of rehabilitation
Rehabilitation will increase muscle blood flow	Increase peripheral muscle blood flow measured by plethysmography.	3 months of rehabilitation
Reduction in the number of symptomatic episodes of ischemia	Reduction in the number of episodes of ischemia, reduction of daily sublingual nitrate intake.	3 months of rehabilitation
Reduction of the daily consumption of sublingual nitrate	Reduction of daily sublingual nitrate intake.	3 months of rehabilitation
Improve the functional class of Refractory Angina	Improve the functional class decrease of angina (according to Canadian Cardiovascular Society classification)	3 months of rehabilitation

Collaborators and Investigators

• Sponsor: Hospital Israelita Albert Einstein
• Collaborators: Fundação de Amparo à Pesquisa do Estado de São Paulo; Instituto do Coracao
• Investigators: Principal Investigator: Luciana Janot de Matos, Dra, Hospital Israelita Albert Einstein; Principal Investigator: Luciana Janot de Matos, Dra, InCor Heart Institute

Publications and helpful links

General Publications

• de Assumpção CRA, do Prado DML, Jordão CP, Dourado LOC, Vieira MLC, Montenegro CGSP, Negrão CE, Gowdak LHW, De Matos LDNJ. Cardiopulmonary exercise test in patients with refractory angina: functional and ischemic evaluation. Clinics (Sao Paulo). 2022 Feb 5;77:100003. doi: 10.1016/j.clinsp.2021.100003. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): July 28, 2020
• Study Completion (Actual): February 1, 2022

Study Registration Dates

• First Submitted: June 5, 2017
• First Submitted That Met QC Criteria: July 12, 2017
• First Posted (Actual): July 17, 2017

Study Record Updates

• Last Update Posted (Actual): February 11, 2022
• Last Update Submitted That Met QC Criteria: February 10, 2022
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Rehabilitation; Refractory Angina
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris
• Other Study ID Numbers: 2014/00345-0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No