Twelve-month follow-up results from the SIRONA 2 clinical trial.

AIMS: In the SIRONA 2 trial, the safety and efficacy of pulmonary artery (PA) pressure (PAP)-guided heart failure (HF) management using a novel PAP sensor were assessed at 30 and 90 days, respectively, and both endpoints were met. The current study examines the prespecified secondary endpoints of safety and accuracy of the PA sensor along with HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance through 12 months. METHODS AND RESULTS: SIRONA 2 is a prospective, multi-centre, open-label, single-arm trial evaluating the Cordella™ PA Sensor System in 70 patients with New York Heart Association (NYHA) functional class III HF with a prior HF hospitalization and/or increase of N-terminal pro-brain natriuretic peptide within 12 months of enrolment. Sensor accuracy was assessed and compared with measurements obtained by standard right heart catheterization (RHC). Safety was defined as freedom from prespecified adverse events associated with use of the Cordella PA Sensor System and was assessed in all patients who entered the cath lab for PA sensor implant. HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance were also assessed. At 12 months, there was good agreement between the Cordella PA Sensor System and RHC, with the average difference for mean PAP being 2.9 ± 7.3 mmHg. The device safety profile was excellent with 98.4% freedom from device/system-related complications. There were no pressure sensor failures. HF hospitalizations and mortality were low with a rate of 0.33 event per patient year. Symptoms as assessed by NYHA (P < 0.0001) and functional capacity as measured by 6 min walk test (P = 0.02) were significantly improved. Patients' adherence to daily transmissions of PAP and vital signs measurements was 95%. CONCLUSIONS: Long-term follow-up of the SIRONA 2 trial supports the safety and accuracy of the Cordella PA Sensor System in enabling comprehensive HF management in NYHA class III HF patients.

Rationale and Design of the Proactive-HF Trial for Managing Patients With NYHA Class III Heart Failure by Using the Combined Cordella Pulmonary Artery Sensor and the Cordella Heart Failure System.

BACKGROUND: Optimizing guideline-directed medical therapy (GDMT) and monitoring congestion in patients with heart failure (HF) are key to disease management and preventing hospitalizations. A pulmonary artery pressure (PAP)-guided HF management system providing access to body weight, blood pressure, heart rate, blood oxygen saturation, PAP, and symptoms, may provide new insights into the effects of patient engagement and comprehensive care for remote GDMT titration and congestion management. METHODS: The PROACTIVE-HF study was originally approved in 2018 as a prospective, randomized, controlled, single-blind, multicenter trial to evaluate the safety and effectiveness of the Cordella PAP Sensor in patients with HF and with New York Heart Association (NYHA) functional class III symptoms. Since then, robust clinical evidence supporting PAP-guided HF management has emerged, making clinical equipoise and enrolling patients into a standard-of-care control arm challenging. Therefore, PROACTIVE-HF was changed to a single-arm trial in 2021 with prespecified safety and effectiveness endpoints to provide evidence for a similar risk/benefit profile as the CardioMEMS HF System. CONCLUSION: The single-arm PROACTIVE-HF trial is expected to further demonstrate the benefits of PAP-guided HF management of patients with NYHA class III HF. The addition of vital signs, patient engagement and self-reported symptoms may provide new insights into remote GDMT titration and congestion management.

Intraplatelet reactive oxygen species, mitochondrial damage and platelet apoptosis augment non-surgical bleeding in heart failure patients supported by continuous-flow left ventricular assist device.

Non-surgical bleeding (NSB) is the most common clinical complication among heart failure (HF) patients supported by continuous-flow left ventricular assist devices (CF-LVADs). Understanding the role of platelet functionality contributing to NSB after CF-LVAD implantation is crucial for prevention and management of this adverse event. The aim of this study was to examine the role of intraplatelet reactive oxygen species (ROS) and platelet damage on the incidence of bleeding events after CF-LVAD implantation in HF patients. We recruited 25 HF patients implanted with CF-LVADs and 11 healthy volunteers as the control. Intraplatelet ROS generation, platelet mitochondrial damage and platelet apoptosis were quantified by flow cytometry. Among 25 patients, 8 patients developed non-surgical bleeding within one month after CF-LVAD implantation. Intraplatelet ROS, depolarized and apoptotic platelet were found to be pre-existing conditions in all baseline samples of the 25 HF patients when compared to the healthy volunteers. There was no significant difference in the levels of ROS between the non-bleeder and the bleeder groups prior to CF-LVAD implantation, although we noticed 2-fold and 1.5-fold rise in depolarized and apoptotic platelets, respectively, in the bleeder group compared to those in the non-bleeder group. Post implant levels of intraplatelet ROS, depolarized and apoptotic platelets increased and remained elevated in the bleeder group, whereas periodic decreases were noticed in the non-bleeder group, suggesting the potential role of platelet damage on bleeding incidence. ROS generation after CF-LVAD implantation positively associated with platelet apoptosis (ρ = 0.4263, p = 0.0023) and depolarized platelets (ρ = 0.4774, p = 0.0002), especially the latter. In conclusion, elevated intraplatelet ROS and platelet damage may be linked to the NSB among HF patients supported by CF-LVAD. These results provide mechanistic insights into the bleeding complication in patients with CF-LVAD support.