heaRtInsiGHT Alert guIDE: RightAIDE Application of the HeartInsight Acute Heart Failure Predictor in Routine Clinical Practice: Organizational Models and Workflow.

Study Title:

heaRtInsiGHT Alert guIDE: RightAIDE - Application of the HeartInsight acute heart failure predictor in routine clinical practice, organizational models and workflow

Background and Rationale:

Heart failure is a chronic and progressive condition characterized by the inability of the heart to adequately pump blood to meet the body's needs. It is associated with frequent hospitalizations due to episodes of acute decompensation, which substantially contribute to the burden on healthcare systems.

Recent technological advances have enabled the development of predictive algorithms that analyze remotely transmitted data from implanted cardiac devices to forecast clinical events. HeartInsight™ is an integrated algorithm within Biotronik ICDs and CRT-Ds that evaluates trends in seven key physiological parameters: mean and nocturnal heart rate, atrial high-rate episodes, daily physical activity, heart rate variability, ventricular extrasystoles, and thoracic impedance.

HeartInsight, validated in the SELENE HF study, demonstrated the ability to predict 66 percent of heart failure hospitalizations, providing a median lead time of 42 days. Despite this evidence, prospective real-world data on the integration of HeartInsight within routine clinical practice, supported by a structured clinical workflow, are currently lacking.

Study Design:

RightAIDE is a prospective, multicenter, observational registry designed to evaluate the clinical application of HeartInsight in standard practice. Fourteen Italian centers with expertise in remote monitoring of cardiac implantable devices will participate. Additional centers may be added if needed without constituting a protocol amendment.

Approximately 100 patients will be enrolled and followed for 12 months. Enrollment will be non-consecutive to reflect clinical practice. No investigational procedures or additional diagnostic tests will be required. All devices and software used in this study are CE marked and will be used within their approved indications.

Study Objectives:

The primary objective is to quantify the proportion of HeartInsight alerts that lead to a clinical action. Clinical actions include device reprogramming, reinforcement or optimization of prescribed therapy, unscheduled outpatient visits, additional diagnostic testing, or hospitalization linked to the alert period.

Secondary objectives include evaluating the frequency of alerts, the cumulative duration of alert periods per patient, the number of patient interviews during alert periods, hospitalization rates during and outside alert periods, and the proportion of patients able to install and effectively use the HeartInsight Patient App.

Endpoints:

Primary Endpoint: Percentage of actionable alerts, defined as alerts that result in one or more predefined clinical actions.

Secondary Endpoints: Frequency of alerts per patient, cumulative duration of alert periods, number of telephone interviews conducted in response to alerts, frequency of cardiovascular hospitalizations during and outside alert periods, and rate of Patient App utilization.

Study Procedures:

After verification of eligibility and signing of informed consent, patients will be instructed on the use of the Home Monitoring system, the HeartInsight algorithm, and the optional installation of the Patient App. Patients will be followed for 12 months with remote monitoring and regular clinical visits according to standard care.

When an alert is triggered, the predefined workflow will guide clinical response, including verification of device data, assessment of patient compliance and symptoms, and appropriate interventions as deemed necessary by the treating physician.

Reasons for early withdrawal include interruption of Home Monitoring transmissions for more than 90 days, device removal or replacement, withdrawal of consent, or death.

Sample Size and Statistical Analysis:

Based on prior data from the SELENE HF study indicating an alert rate of approximately 1.1 per patient-year, 91 patients are expected to generate around 100 alerts during the 12-month follow-up. To account for an estimated 10 percent dropout rate, the planned enrollment is 100 patients.

Descriptive statistics will summarize baseline and outcome data. Continuous variables will be reported as quartiles and medians, while categorical variables will be reported as frequencies and percentages. Point estimates and 95 percent confidence intervals will be provided for actionable alert rates and for the incidence of clinical interventions. Statistical analyses will be performed using R software.

Data Management and Confidentiality:

Study data will be collected through electronic case report forms. Personal identifiers will be stored separately from coded study data. Data will be securely stored and retained for up to 15 years in accordance with regulatory requirements.

Ethical Considerations:

The study will be conducted in accordance with the Declaration of Helsinki, Good Clinical Practice (ICH E6 R2), and applicable national regulations. Written informed consent is required prior to participation. Any protocol amendments that could impact patient safety, study endpoints, or key procedures will require ethics committee approval.

Monitoring and Dissemination:

Monitoring will be performed according to a predefined plan to ensure data integrity and protocol compliance. Study results will be disseminated through scientific conferences and peer-reviewed journals. Authorship of publications will be assigned according to predefined performance criteria among participating centers.

Duration:

The enrollment period is planned for approximately 12 months. Each patient will be followed for 12 months, resulting in an overall study duration of approximately 24 months.

• Frequency of HeartInsight Alerts [Time frame: 1 year]
• Cumulative Duration of Alert Periods per Patient [Time frame: 1 year]
• Frequency of Telephone Contacts for Patient Interviews [Time frame: 1 year]
• Frequency of Cardiovascular Hospitalizations [Time frame: 1 year]
• Proportion of Patients Using the HeartInsight Patient App [Time frame: 1 year]