Background: For a decade, despite results from many studies, telemedicine systems have suffered from a lack of recommendations in chronic heart failure (CHF) care because of variable study results. Another limitation is the hospital-based architecture of most telemedicine systems. The TwoCan Pulse™ system marketed by e-Device uses an algorithm based on daily weight, transcutaneous oxygen measurement (TCOM) and heart rate to detect and treat acute heart failure (AHF) in CHF patients as early on as possible.Objective: The aim of this study is to determine the efficacy of the TwoCan Pulse™ device in detecting clinical destabilization in real-life settings (out-of-hospital management) without generating too many false positive alerts.Methods: All patients self-monitoring at home using the TwoCan Pulse™ system after a congestive acute heart failure event treated in a private cardiology clinic in Tours, France, between March 2020 and March 2021, with at least 75% compliance on daily measurements, were included retrospectively. A new-onset AHF was defined by the presence of at least one of the following criteria: transcutaneous oxygen saturation loss defined as TCOM under 90%, rise of cardiac frequency above 110 beatsper-minute (bpm), weight gain of at least 2 kilograms, and symptoms of congestive AHF described over the phone. An AHF alert was generated when criteria reached our definition of new-onset acute congestive heart failure.Results: A total of 111 consecutive patients (70 men), with a mean age of 76.60 [69.5, 83.4] years, receiving TwoCan Pulse™ were included. Thirty-nine patients (35.1%) reached HF warning level, and 28 patients (25%) suffered from confirmed HF destabilization during follow-up. No patient suffered from AHF without being detected by TwoCan Pulse™. Among incorrect AHF alerts, 5 patients (45.4%) had taken inaccurate measurements, 3 patients (27.2%) suffered from supraventricular arrhythmia, one patient (9.1%) suffered from a pulmonary bacterial infection, and one patient (9.1%) contracted COVID-19. A weight gain of at least 2 kilograms within 4 days was significantly associated with a correct AHF alert (p = 0.0038), and a heart rate of more than 110 bpm was more significantly associated with an incorrect AHF alert (p = 0.007).Conclusions: This single-center study highlighted the efficacy of the TwoCan Pulse™ telemedicine system in detecting and treating quickly cardiac instability complicating the course of chronic heart failure, by detecting new onsets of acute heart failure as well as of supraventricular arrhythmia, thus helping cardiologists provide better follow-up to ambulatory patients.