Patient-centered Personalized Cardiac Rehabilitation in Post Acute Coronary Syndrome (BREAK-trial)

The primary endpoint of the study will be a composite functional capacity score, designed to capture the overall improvement in cardiorespiratory fitness following the rehabilitation intervention.

This composite score will integrate the standardized change (from baseline to the end of the intervention) in the following four variables:

• Peak oxygen uptake (VO₂ peak, in ml/kg/min), measured via cardiopulmonary exercise testing (CPET).
• Six-minute walk distance (6MWD, in meters), assessed using the six-minute walk test.
• Maximal metabolic equivalents (METs), achieved during CPET.
• Exercise test duration (in minutes), defined as the total time sustained during the treadmill or cycle ergometer test under a standardized, symptom-limited protocol.

Each of these variables will be converted to z-scores based on the distribution of change scores in the study population. The composite score will be calculated as the mean of the four standardized values

Adherence to physical activity will be evaluated with the International Physical Activity Questionnaire (IPAQ). The IPAQ classifies individuals into three categories of physical activity level based on intensity, frequency, and total energy expenditure (measured in MET·minutes/week):

Category 1: Low Physical Activity:

The person does not meet the criteria for moderate or high physical activity.

Considered sedentary or insufficiently active.

Category 2: Moderate Physical Activity. A person meets any of the following:

• 3 days/week of vigorous activity ≥20 minutes/day, or
• 5 days/week of moderate activity and/or walking ≥30 minutes/day, or
• 5 days/week of any combination of walking, moderate, or vigorous activity totaling ≥600 MET·minutes/week.

Category 3: High Physical Activity. A person meets either:

• 3 days/week of vigorous activity accumulating ≥1,500 MET·minutes/week, or
• 7 days/week of any combination of walking, moderate or vigorous activity totaling ≥3,000 MET·minutes/week

According to pedometer readings which will be given to patients (steps/day), physical activity is categorized as follows:

Sedentary or inactive < 5,000 steps/day Low active 5,000-9,999 steps/day Active 10,000-12,499 steps/day Very active ≥ 12,500 steps/day

Psychological status will be evaluated for screening of anxiety and depression (PHQ-9 and GAD-7 scales).

The PHQ-9 is a 9-item questionnaire used to screen for depression. Each item is scored from 0 (not at all) to 3 (nearly every day), with a total score range of 0-27. Cut-off points:

5-9: mild depression 10-14: moderate depression 15-19: moderately severe depression 20-27: severe depression

The GAD-7 is a 7-item scale assessing generalized anxiety. Each item is scored 0-3 (same as PHQ-9), total score range: 0-21. Cut-off points:

5-9: mild anxiety 10-14: moderate anxiety 15-21: severe anxiety

A score ≥10 on either scale suggests clinically relevant symptoms, warranting further evaluation.

ChatGPT Plus To assess dietary changes, we will use two validated tools: the DEBQ (Dutch Eating Behavior Questionnaire) and the PREDIMED Mediterranean Diet questionnaire.

The DEBQ evaluates emotional, external, and restrained eating behaviors using 33 items rated on a 5-point scale (from "never" to "very often"). It helps identify if a patient eats more in response to emotions, sensory cues, or dieting efforts. Higher scores in each subscale indicate a stronger influence of that behavior on eating patterns.

The PREDIMED questionnaire has 14 questions and measures adherence to the Mediterranean diet. Each healthy habit (e.g., using olive oil, eating fruits/vegetables, low processed food intake) scores 1 point.

Scores ≥9 = good adherence, <9 = low adherence.

These tools allow monitoring of diet quality and behavior-related eating changes

Nutritional status will be evaluated with the use of bioimpedanciometry (BIA), monitoring changes in body composition such as % of muscle and fat mass.

Sarcopenia will be assessed in patients using handgrip dynamometry, expressed in kilograms (kg). Handgrip strength (HGS) is a validated proxy for overall muscle strength and is widely used in clinical settings for sarcopenia screening. According to the international norms published by Tomkinson et al. (2025), cut-off values will be based on sex- and age-specific percentiles.

Patients with HGS values below the 20th percentile for their age and sex will be considered at risk of sarcopenia. This threshold aligns with evidence suggesting that the lowest quintile is predictive of poorer health outcomes and increased mortality. These percentiles provide a robust, standardized reference to guide early intervention.

Frailty will be assessed using the Short Physical Performance Battery (SPPB), a validated tool that evaluates lower extremity function through three components:

Balance (side-by-side, semi-tandem, tandem stand)

Gait speed (usual pace over 4 meters)

Chair stands (time to rise from a chair five times)

Each component is scored from 0 to 4, giving a total score range of 0 to 12 (higher scores = better function).

Cut-off points for frailty classification:

0-6 points: frail

7-9 points: pre-frail

10-12 points: robust

This tool helps identify patients at risk of mobility disability and adverse outcomes and is recommended for use in both research and clinical practice.

Changes in quality of life will be assessed using two validated instruments: the EuroQol-5D (EQ-5D) and the HeartQoL (HRQoL) questionnaire.

(EQ-5D)

This tool evaluates health across 5 dimensions:

Mobility Self-care Usual activities Pain/discomfort Anxiety/depression

Each dimension has 3 levels: no problems, some problems, and extreme problems. It also includes a visual analogue scale (VAS) from 0 (worst imaginable health) to 100 (best imaginable health), allowing patients to rate their overall health state. Higher scores indicate better perceived health.

HRQoL

The HRQoL is a disease-specific questionnaire for patients with ischemic heart disease. It has 14 items divided into two dimensions:

Physical (10 items) Emotional (4 items)

Each item is scored from 0 (worst HRQoL) to 3 (best HRQoL). Scores are averaged for each subscale and the global score; higher scores reflect better quality of life. Changes over time can reflect improvements or deterioration in health perception

Sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI), a standardized questionnaire that evaluates sleep patterns over the past month.

The PSQI consists of 19 self-rated items grouped into 7 components:

Subjective sleep quality Sleep latency Sleep duration Habitual sleep efficiency Sleep disturbances Use of sleeping medication Daytime dysfunction

Each component is scored from 0 to 3, producing a global score ranging from 0 to 21.

Scores ≤5: good sleep quality Scores >5: poor sleep quality

Higher scores reflect worse sleep quality. The PSQI is widely used in both research and clinical practice to monitor sleep-related changes and identify individuals with potential sleep disorders.

Sexual dysfunction will be assessed using validated, sex-specific questionnaires:

For men: IIEF (International Index of Erectile Function)

The IIEF evaluates male sexual function over the past 4 weeks using 15 items distributed across 5 domains:

Erectile function (items 1-5, 15) Orgasmic function (items 9-10) Sexual desire (items 11-12) Intercourse satisfaction (items 6-8) Overall satisfaction (items 13-14)

Each item is scored from 0 or 1 to 5, with higher scores indicating better sexual function.

Erectile dysfunction is usually classified as:

1-10: severe 11-16: moderate 17-25: mild to moderate 26-30: normal

For women: FSM (Female Sexual Function Questionnaire)

This tool consists of 19 items grouped into 6 domains:

Desire (items 1-2) Arousal (items 3-6) Lubrication (items 7-10) Orgasm (items 11-13) Satisfaction (items 14-16) Pain (items 17-19)

Some items are reverse-scored (8, 10, 12, 17-19). Higher total and subscale scores indicate better sexual function.

Readmission Rate (All-Cause and Cardiovascular)

Patient outcomes will include evaluation of hospital readmissions, classified as:

All-cause readmissions: any reason for hospital admission after discharge. Cardiovascular readmissions: admissions due to heart-related conditions (e.g., heart failure, myocardial infarction, arrhythmia).

We will register both the rate (percentage of patients readmitted) and the total number of readmissions. A lower readmission rate reflects better clinical stability and care continuity.

Mortality (All-Cause and Cardiovascular)

Mortality will be monitored and classified into:

All-cause mortality: death from any origin. Cardiovascular mortality: death due to cardiac or vascular causes (e.g., sudden cardiac death, stroke, heart failure).

These indicators will evaluate patient prognosis and treatment effectiveness over the follow-up period.

Patient adherence and retention will be evaluated as follows:

1.1 Adherence analysis: the total percentage of exercise sessions attended in both groups (conventional vs domiciliary program). And also adherence to the different types of sessions (respiratory, relaxation, aerobic and strength) 1.2. Retention rate: the number of participants who finish the training divided by the number of randomized patients.

Patient's experience with both the cardiac rehabilitation program and the use of technology will be assessed using a LIKERT scale (1 Not at all to 5 A lot) asking the following questions:

• How do you think a cardiac rehabilitation program can impact your health?
• How do you think the use of information technology can impact your health?

The results will be analyzed before starting the program and at the end to determine if patient's impression has changed.