Home-Based Clinical Management of Cardiac Complications in Systemic Sclerosis

Adherence and compliance will be assessed by tracking the frequency and completeness of data entries in the digital platform. This includes biweekly symptom reporting, completion of the 1-minute sit-to-stand test (1MSTS), and compliance with ECG monitoring.

Technical feasibility will be evaluated based on the occurrence of technical failures, data loss, and missing entries in the home monitoring system. The frequency of reported technical issues and the ability of participants to successfully complete monitoring tasks will be recorded.

Agreement between home-based 1-minute sit-to-stand test (1MSTS) and hospital-based 6-minute walk distance (6MWD) in assessing exercise capacity will be evaluated using correlation analysis (e.g., Pearson or Spearman correlation) and Bland-Altman plots to assess agreement. A regression model may be applied to explore the predictive relationship between 1MSTS (number of repetitions) and 6MWD (distance in meters).

Unit of Measure:

• Primary Unit: Agreement (correlation coefficient)
• Secondary Units: 1MSTS (number of repetitions), 6MWD (meters)

Agreement between home-based and hospital-based peripheral oxygen saturation (SpO₂) at rest and the lowest (nadir) value during the tests.

Unit of Measure: Percentage (%)

Agreement between home-based and hospital-based heart rate measurements at rest, at maximum during the tests, and one minute after the tests.

Unit of Measure: Beats per minute (bpm)

Agreement between home-based and hospital-based Borg dyspnea scale scores during the tests.

Unit of Measure: Borg dyspnea scale score

Agreement between home-based and hospital-based Visual Analogue Scale (VAS) scores for dizziness and palpitations from 0 - 10 cm with higher values indicating more symptoms.

Unit of Measure: VAS score (range: 0-10 cm)

Agreement between home-based and hospital-based NT-proBNP measurements. Unit of Measure: pg/mL

Patient satisfaction with home monitoring will be assessed using the Client Satisfaction Questionnaire (CSQ-8), which evaluates overall satisfaction with the home monitoring system. The CSQ-8 consists of eight items, each rated on a 4-point scale, with a total score range of 8 to 32. Higher scores indicate greater satisfaction.

Unit of Measure: CSQ-8 total score (range: 8-32)

Usability, feasibility, and perceived impact of home monitoring will be assessed using a custom-designed questionnaire. This questionnaire evaluates:

• Usability (ease of use, technical difficulties, and disease-related limitations affecting use)
• Feasibility (time commitment, disruption to daily life, need for additional guidance)
• Impact (perceived usefulness for disease management, confidence in self-care, and emotional responses such as anxiety) Responses will be recorded on Likert scales (1-5 or 1-4, depending on the item).

Unit of Measure: Individual questionnaire item scores (Likert scale 1-5 or 1-4)

The frequency and reasons for interactions between participants and healthcare providers related to home monitoring will be tracked. These interactions may include technical difficulties, concerns about home-monitoring results, and symptom-related consultations.

The EmPHasis-10 questionnaire will be used to assess changes in disease burden and health-related quality of life (HRQoL) for patients with pulmonary arterial hypertension. The total score ranges from 0 to 50, with higher scores indicating worse HRQoL.

Unit of Measure: EmPHasis-10 total score (range: 0-50)

The Modified Medical Research Council (mMRC) Dyspnea Scale will be used to assess changes in perceived breathlessness. The scale ranges from 0 to 4, with higher scores indicating greater dyspnea severity.

Unit of Measure: mMRC score (range: 0-4)

Patient-reported symptoms, including dyspnea, orthopnea, fatigue, dizziness, syncope, palpitations, chest pain, and edema will be assessed using Visual Analogue Scales (VAS, 0-10 cm), where higher values indicate more severe symptoms.

Unit of Measure: VAS score (range: 0-10 cm)

The EULAR Systemic Sclerosis Impact of Disease (ScleroID) questionnaire will be used to assess disease burden in patients with systemic sclerosis. The ScleroID evaluates ten health dimensions. Each dimension is rated on a numeric rating scale (NRS) from 0 to 10, where higher scores indicate greater disease impact. To calculate the total ScleroID score, each dimension's NRS score is multiplied by a predefined weight, reflecting its relative importance. The weighted scores are summed, resulting in a composite score ranging from 0 (no impact) to 10 (maximum impact).

Unit of Measure: ScleroID total score (range: 0-10)

The EuroQol EQ-5D-5L descriptive system will be used to assess changes in health-related quality of life (HRQoL) across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a 5-level scale from no problems (Level 1) to extreme problems (Level 5). A country-specific value set will be used to calculate an index value, typically ranging from less than 0 (worse than death) to 1 (perfect health).

Unit of Measure: EQ-5D-5L index score (range: <0 to 1)

The EQ Visual Analogue Scale (EQ VAS) will be used to assess self-rated health status. Participants will rate their overall health on a vertical scale ranging from 0 (worst imaginable health) to 100 (best imaginable health).

Unit of Measure: EQ VAS score (range: 0-100)

The Health Assessment Questionnaire Disability Index (HAQ-DI) will be used to assess changes in functional disability. The HAQ-DI evaluates functional ability across eight domains of daily activities: (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities). The total score ranges from 0 (no disability) to 3 (severe disability). The final HAQ-DI total score is the average of the highest scores in each domain, ranging from 0 (no disability) to 3 (severe disability). If assistive devices or assistance are required, the minimum score for that domain is adjusted to 2.

Unit of Measure: HAQ-DI total score (range: 0-3)

The Hospital Anxiety and Depression Scale (HADS) will be used to assess changes in emotional well-being. The HADS consists of two subscales (anxiety and depression), each ranging from 0 to 21, with higher scores indicating greater anxiety or depression.

Unit of Measure: HADS total score (range: 0-42) and subscale scores (0-21)

PAH progression will be defined using adapted SERAPHIN criteria, including: (i) death, (ii) lung transplantation, (iii) atrial septostomy, (iv) initiation of parenteral prostanoids, or (v) ≥15% decline in 6MWD from baseline plus worsening PAH symptoms (increased WHO-FC or signs of right heart failure unresponsive to oral diuretics) or initiation of a new PAH-specific therapy (oral/inhaled prostanoids, PDE-5is, ERAs, or sGCs). Progression events will be recorded retrospectively at the final study visit.

PAH events will be recorded as clinical worsening requiring healthcare utilization. Events include non-elective hospital admission or emergency department visits due to PAH, initiation of new PAH-specific therapy, and initiation of long-term oxygen therapy (LTOT). PAH events will be recorded retrospectively at the final study visit.

Changes in WHO Functional Class (WHO-FC) will be assessed to evaluate changes in symptom severity and functional capacity in pulmonary hypertension. WHO-FC is categorized as:

• Class I: No limitation of physical activity
• Class II: Mild limitation
• Class III: Marked limitation
• Class IV: Unable to perform physical activity without symptoms Unit of Measure: WHO-FC classification (Ordinal scale: I-IV)

The 6-minute walk distance (6MWD) test measures changes in exercise capacity. The total distance walked (in meters) over 6 minutes will be recorded.

Unit of Measure: Distance in meters (m)

The 1-minute sit-to-stand test (1MSTS) will assess changes in functional capacity by measuring the number of times a participant can stand up from a chair in 1 minute.

Unit of Measure: Number of repetitions

Pulmonary function tests (PFTs) will assess changes in lung function by measuring:

• Forced Vital Capacity (FVC, % predicted)
• Diffusing capacity of the lung for carbon monoxide (DLCO, % predicted) Unit of Measure: Percentage of predicted value (% predicted)

Changes in NT-proBNP levels will be assessed as a biomarker for cardiac function and disease progression.

Unit of Measure: NT-proBNP concentration (pg/mL)

Changes in risk stratification will be assessed using the ESC/ERS four-strata model, which categorizes patients based on the mean score into:

• Low risk (<1.50)
• Intermediate-low risk (1.50-2.49)
• Intermediate-high risk (2.50-3.49)
• High risk (≥3.50) The classification is based on cut-off levels of WHO Functional Class (WHO-FC), 6-minute walk distance (6MWD), and NT-proBNP. Each parameter is graded 1 to 4, with the mean score defining the risk category. The model estimates 1-year mortality ranging from 0-3% (low risk) to >20% (high risk).

Unit of Measure: Risk category (low/intermediate-low/intermediate-high/high)

Changes in home-based clinical measures from baseline to week 12, focusing on 1-minute sit-to-stand test (1MSTS) performance over time.

This outcome will determine cut-off values for the 1-minute sit-to-stand test (1MSTS) that correspond to established 6-minute walk distance (6MWD) thresholds used in the ESC/ERS four-strata risk stratification model. The optimal 1MSTS cut-offs will be determined using receiver operating characteristic (ROC) curve analysis and Youden's index to identify thresholds corresponding to established 6MWD cut-off values. Correlation and regression analyses will also be used to assess the relationship between 1MSTS and 6MWD

• Primary Unit: 1MSTS cut-off values (number of repetitions)
• Reference Unit: 6MWD (meters)

This outcome will assess the agreement between home-based risk stratification (mMRC, 1MSTS, NT-proBNP) and hospital-based risk stratification (WHO-FC, 6MWD, NT-proBNP) using the ESC/ERS four-strata model. Patients will be categorized based on the mean score into:

• Low risk (<1.50)
• Intermediate-low risk (1.50-2.49)
• Intermediate-high risk (2.50-3.49)
• High risk (≥3.50)

Risk classification for home-based measures will follow:

• mMRC vs. WHO-FC: The mMRC 0-4 scale will be mapped to the WHO-FC I-IV scale based on established correlations from the COMPERA 2.0 model (mMRC 0-1 = WHO-FC I-II, mMRC 2-3 = WHO-FC III, mMRC 4 = WHO-FC IV).
• NT-proBNP: Same cut-off values will be used for home-sampled and hospital-drawn blood.
• 1MSTS vs. 6MWD: Cut-off values will be determined based on findings from Outcome Measure 29.

Unit of Measure: Risk category (low/intermediate-low/intermediate-high/high)

The reproducibility of home-based measures will be assessed by comparing patient-reported mMRC vs. physician-reported WHO-FC to evaluate inter-rater agreement in functional classification and home-based 1MSTS vs. hospital-based 1MSTS to assess reproducibility across different settings.

Home ECG monitoring will be used to assess the frequency and type of rhythm disturbances, daytime vs. nighttime heart rate (HR), heart rate variability (HRV), and correlation of HR/HRV with hospital-based measures, risk stratification, and PAH progression.