Leader: Andrea Ungar (UNIFI); Other collaborator(s): Francesca Cecchi (UNIFI); Andrea Giustina (UNISR); Guglielmo Bonaccorsi (UNIFI); Alessio Faralli (UNIFI)
The general objective is that of the identification of frailty and multidisciplinary intervention in patients with cardiovascular diseases, in order to identify the markers and predictors of frailty and to assess: 1. the prevalence of frailty in older adults according to different measure tools and verify the prognostic role of frailty on functional decline. 2. prognostic role of frailty on diverse adverse clinical outcomes. 3. the relationship between cardiovascular diseases and different adverse clinical outcomes by frailty status
Brief description of the activities and of the intermediate results: In November, we conducted a preliminary analysis of the data collected thus far in the REMOTE 2 study. Additionally, following the preliminary analysis conducted this summer in the REMOTE 1 study, we resumed participant recruitment and the collection of follow-up data for patients with Implantable Loop Recorders, specifically those with carotid sinus hypersensitivity and a history of syncope and falls.
In December, we progressed with the recruitment and follow-up of patients in the MULTI-REMOTE CONTROL project. From December 13th to 16th, we also attended the SIGG National Congress in Florence, where we presented the preliminary results of the REMOTE 1 study.
In January our group has carried out the MULTI-REMOTE study, focused on the management and monitoring of cardiovascular diseases in the older population. Specifically, we have continued enrolments in the two sub-studies REMOTE 1 and 2. Additionally, we have conducted a preliminary analysis of the data from the REMOTE 2 study and we have submitted an abstract with the preliminary data from the REMOTE 1 study to the Age-IT Congress in Venice, scheduled for next May.
In February 2024, we continued enrolments in the REMOTE 2 study and collected follow-up data from patients enrolled in the REMOTE 1 study thus far.
During March 2024, we continued the enrolment/data collection work for both studies. We have also finalized purchase requests using PNRR funds for some materials useful for research purposes (glucose monitoring systems) to be used in the multiparametric monitoring project for the elderly. Additional purchases will be completed soon.
Main policy, industrial and scientific implications: These research activities aim to promote and expand the evidence on the role of implantable and wearable monitoring devices in frail older patients with multiple cardiovascular comorbidities and beyond.
During the second quarter of 2024, progresses was made in data collection and analysis of MULTI-REMOTE study. The team received confirmation of the acceptance of preliminary findings from the REMOTE1 sub-study for presentation at the national AgeIT Congress. Additionally, the Finapres® NOVA hemodynamic monitoring system, funded by the PNRR project, was delivered.
In May, the team participated in the Age-IT Conference at Ca' Foscari University in Venice, where they presented the preliminary results of the REMOTE1 sub-study. These results were based on 80% of the enrolled population, including initial follow-up data. The conference also provided valuable opportunities for networking with researchers from across Italy, laying the groundwork for future collaborations.
Work on the REMOTE2 sub-study also advanced, with around 60% of the sample size enrolled, and follow-up data analysis began. By June, preliminary analyses of the REMOTE2 follow-up data were ongoing, with the aim of producing reports and abstracts for conferences scheduled in the second half of the year. The team also submitted a contribution based on REMOTE1 to the EUGMS 2024 Congress.
Meanwhile, technical support for the Finapres® Nova system was delayed due to procurement issues. Lastly, several coordination meetings were held with the DIEF and DIDA working groups at the University of Florence to advance the development of the older glycaemic monitoring project.
During the third quarter of 2024, the team moved forward with the ongoing research projects. In July, confirmation was received for the presentation of the latest updates from the REMOTE1 sub-study at the EUGMS 2024 Congress. The team also completed statistical analyses for the REMOTE2 sub-study and submitted an abstract to the 2024 National SIGG Congress. In August, continuous glucose monitoring (CGM) devices were received to start with a new study project, investigating the correlation between intensive glycaemic control and the risk of falls in frail elderly individuals. This study is being conducted in collaboration with the DIDA and DIEF groups at the University of Florence. Meanwhile, research activities on both the REMOTE1 and REMOTE2 studies continued.
In September, the team participated in the EUGMS 2024 Congress in Valencia, presenting the preliminary results of the REMOTE1 sub-study as a digital poster. Additionally, documentation for the CGM and falls study was submitted to the local Ethics Committee for approval.
During the period October–December 2024, the second analysis of the data collected so far in the REMOTE 2 study was conducted, and the results were presented as a contribution to the "Age Florence" event held in Florence on December 19, 2024. We are currently awaiting the collection of the final follow-up data from the REMOTE 1 study, which will allow us to proceed with the final phase of the study over the course of the coming year.
In December, the project on CGM and falls in the elderly was also reviewed during the session of the local Ethics Committee. On that occasion, however, a provisional opinion was issued, and our team is currently working on optimizing the protocol in accordance with the observations provided by the Ethics Committee.
We are still waiting for technical support for the Finapres® Nova system, as unfortunately, the university offices are significantly delayed in processing the administrative procedures.
During the period January – March 2025, both studies of the “MULTI-REMOTE STUDY” progressed as planned.
For the REMOTE 1 study, the enrollment phase was completed, achieving the target sample size (58 patients with implantable loop recorders [ILRs], a history of suspected reflex syncope, and evidence of cardioinhibitory carotid sinus hypersensitivity [CI-CSH] as determined by carotid sinus massage). We have also nearly completed the data collection phase for the remote monitoring follow-up of these patients (the participating centers are currently sending us the final datasets). Once all follow-up data are collected, we will proceed with the final analysis. This will involve a comparison with a historical cohort of ILR patients enrolled for other reasons, with the aim of assessing the correlation between asystole induced by carotid sinus massage and the mechanism underlying spontaneous syncopal episodes in CI-CSH patients.
Enrollment has also been completed for the REMOTE 2 study (203 patients with a history of cryptogenic stroke and ILRs implanted for atrial fibrillation detection), as has the follow-up data collection. We will carry out the final analysis in the coming months, primarily focusing on the incidence of atrial fibrillation within this cohort and the identification of potential predictive factors.
Regarding the CGM and falls project, we are currently awaiting a second opinion from the local Ethics Committee, following the amendments made to the study protocol.
Finally, in March, technical support of the Finapres® Nova system was completed; the device is currently in use at our clinic.
For the REMOTE 1 study, 62 patients with cardioinhibitory CSH monitored via ILR for ~26 months, were enrolled. Spontaneous asystole detected in 35% (mean pause 7.4 ± 5.0 sec), syncope recurrence in 22 patients (16 with documented asystole, 6 without asystole), 73% of recurrent syncopes were asystolic. Patients with CSH showed a higher (though not statistically significant) incidence of asystolic events compared to matched controls.
Concerning the REMOTE 2 – Cryptogenic Stroke and subclinical AF(SCAF) detection Multicenter, observational real-world study (20 Italian centers), 789 cryptogenic stroke patients monitored via ICM for ~27 months. SCAF was detected in 29%, cumulative rate of 37% at 48 months, 86.5% of episodes were asymptomatic, 95.9% of newly diagnosed patients received anticoagulation. Independent predictors of AF resulted to be: CHA₂DS₂-VASc ≥5, anterior stroke, cortical lesions.
The Multi-Remote Control Study is part of the PhD project of a PhD student in Clinical Sciences at the University of Florence, affiliated with PE8 and the Age-IT project (PNRR – National Recovery and Resilience Plan). The thesis is currently in preparation, based on the study outcomes.
Additional papers acknowledging Age-IT are currently in progress.
The project titled “Continuous Glucose Monitoring and Falls in the Elderly”, developed in collaboration with fellow researchers from Spoke 3 as part of the “THE” project, has been approved by the local Ethics Committee and will start in the next weeks at AOU Careggi, Florence.
During the period July – September 2025, the research activities progressed as planned, with the completion of both sub-studies of the MULTI-REMOTE project.
For the REMOTE 1 study, data collection and final analysis were completed. A total of 62 patients with cardioinhibitory carotid sinus hypersensitivity (CSH) monitored by an implantable loop recorder (ILR) for a mean follow-up of 26 months were included. Spontaneous asystolic episodes were detected in 35% of patients (mean pause 7.4 ± 5.0 seconds). Syncope recurrence occurred in 22 patients, 16 of whom had documented asystole, while 6 had non-asystolic recurrent syncope. Overall, 73% of recurrent syncopal episodes were associated with asystole. Patients with CSH showed a higher, although not statistically significant, incidence of asystolic events compared to matched controls.
The REMOTE 2 study was also completed. This multicenter observational real-world study involved 20 Italian participating centers and included 789 patients with a history of cryptogenic stroke monitored with an insertable cardiac monitor (ICM) for a mean follow-up of 27 months. Subclinical atrial fibrillation (SCAF) was detected in 29% of patients, with a cumulative incidence of 37% at 48 months. Most SCAF episodes were asymptomatic (86.5%). Of the patients with newly detected atrial fibrillation, 95.9% initiated anticoagulation therapy. Independent predictors of AF detection included CHA₂DS₂-VASc score ≥5, anterior circulation stroke, and cortical lesions.
The MULTI-REMOTE Control Study is part of the PhD project of a PhD student in Clinical Sciences at the University of Florence, affiliated with PE8 and the Age-IT project (PNRR). The thesis is currently being developed, based on the study outcomes.
Regarding the CGM and falls project, despite receiving ethical approval and administrative authorization in July 2025, the study could not be initiated within the reporting period due to logistic limitations related to the availability of study devices.
Thanks to the project funding, the following paper is currently under peer review for publication:
During the period October – December 2025, activities focused on the completion and consolidation of the scientific outputs of the MULTI-REMOTE project.
The Ph.D. thesis related to the MULTI-REMOTE Control Study has been completed and submitted and is currently under review by the examiners. The thesis summarizes the results of both the REMOTE 1 and REMOTE 2 studies, further exploring the clinical value of long-term implantable loop recorder (ILR) monitoring in older adults with unexplained syncope, cardioinhibitory carotid sinus hypersensitivity (CSH), and cryptogenic stroke.
REMOTE 1 confirmed that prolonged ILR monitoring in patients with cardioinhibitory CSH identifies a substantial burden of spontaneous asystolic events, detected in approximately 35% of patients, frequently associated with syncope and mainly due to sinus arrest. No significant correlation was observed between carotid sinus massage–induced and spontaneous pauses, supporting the limited predictive value of conventional testing alone and highlighting the added diagnostic role of continuous remote rhythm monitoring.
REMOTE 2 demonstrated a high diagnostic yield of ILRs in patients with cryptogenic stroke, with subclinical atrial fibrillation detected in 29% of cases and a cumulative incidence approaching 37% at long-term follow-up. Most episodes were asymptomatic, and ILR-guided diagnosis enabled the initiation of anticoagulation therapy in nearly all affected patients. Several clinical predictors of AF detection were identified, supporting improved risk stratification and personalized management.
Overall, the thesis provides further real-world evidence supporting the role of prolonged remote cardiac monitoring in diagnostic evaluation, therapeutic decision-making, and secondary prevention in older patients with complex cardiovascular conditions.
During the reporting period, Prof. Andrea Ungar also contributed to dissemination activities by participating as a speaker in the event “Nuove prospettive per la geriatria del futuro” – Dissemination Event, held in Pollica (Salerno, Italy) from 13 to 15 October 2025, organized within the PNRR Age-It program and endorsed by the Italian Society of Gerontology and Geriatrics. The three-day meeting brought together academics, researchers, and young clinicians from leading Italian universities to discuss current challenges in geriatrics, promoting interdisciplinary collaboration, innovative educational approaches, and integrated models of care for healthy and active ageing.
Moreover, the following manuscript has been published:
Mossello E, Rivasi G, Giordano A, Espinoza Tofalos S, Rafanelli M, Lorenzi C, Corsoni V, D'Ambrosi M, Gabellini F, Bulgaresi M, Bonaccorsi G, Benvenuti E, Cavallini MC, Matarrese D, Ungar A. Hospital at home for older frequent hospital users: present and future of a healthcare challenge. Aging Clin Exp Res. 2026;38(1):52. doi: 10.1007/s40520-025-03301-3.
Thanks to the project funding, the following papers have also been published:
Dissemination