Combined Treatment With Hyperbaric Oxygen Therapy and Endovascular Therapy for Patients With Chronic Limb-Threatening Ischemia　- Study Protocol for the HOTFOOT Multicenter Randomized Controlled Trial.

Background: Hyperbaric oxygen therapy (HBOT) is regarded as one of the therapeutic options added to standard care to improve lower-limb outcomes in patients with chronic limb-threatening ischemia (CLTI). However, the current guidelines specify that HBOT should not be offered instead of revascularization to prevent limb loss in CLTI patients. The aim of the HOTFOOT study is to examine the impact of HBOT on wound healing in CLTI patients after successful endovascular therapy (EVT). Methods and Results: The HOTFOOT study is a multicenter prospective randomized open blinded-endpoint trial that is to be conducted at 10 trial centers in Japan between February 2021 and February 2022. This study will enroll 140 patients with CLTI receiving successful EVT. Eligible participants will be allocated 1 : 1 to either the EVT+HBOT or EVT group; participants in the EVT+HBOT group will receive 30 HBOT sessions. The primary outcome is the time to complete wound healing over the 6-month follow-up. Secondary outcomes during the 6-month follow-up are the proportion of patients who achieved complete wound healing, freedom from major lower-limb amputation, amputation-free survival, and freedom from target lesion reintervention. Conclusions: This study is expects to assess whether HBOT, in combination with successful EVT, can improve lower-limb outcomes in CLTI patients.

The P wave morphology in lead V7 on the synthesized 18-lead ECG is a useful parameter for identifying arrhythmias originating from the right inferior pulmonary vein.

Atrial tachyarrhythmias often originate from the superior vena cava (SVC), and right superior (RSPV) and inferior pulmonary veins (RIPV). However, a precise differentiation of those origins is challenging using the standard 12-lead electrocardiogram (ECG) P-wave morphology due to the anatomical proximity. The recently developed synthesized 18-lead ECG provides virtual waveforms of the right-sided chest and back leads. This study evaluated the utility of the synthesized 18-lead ECG to differentiate atrial arrhythmias originating from 3 adjacent structures. Synthesized 18-lead ECGs were obtained during SVC-, RSPV-, and RIPV-pacing in 20 patients with lone paroxysmal atrial fibrillation to develop an algorithm. The P-wave morphologies were classified into 4 patterns: positive, negative, biphasic, and isoelectric. Subsequently, the algorithm's accuracy was validated prospectively in another 40 patients. In retrospective analyses, isoelectric P-waves in synthesized V7 distinguished RIPV-pacing from the others (sensitivity = 81%, specificity = 92%) (first criteria). The P wave morphologies in Leads II (sensitivity = 83%, specificity = 94%) and V1 (sensitivity = 84%, specificity = 80%) distinguished SVC- and RSPV-pacing (second criteria). In a prospective evaluation, the sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV], and accuracy of the first criteria for identifying RIPV-pacing was 97%, 90%, 78%, 99%, and 92%, respectively. The sensitivity, specificity, RPV, NPV, and accuracy of the second criteria (amplitudes > 1 mV in lead II or biphasic P-waves in lead V1) for discriminating SVC- and RSPV-pacing was 66%, 95%, 98%, 50%, and 74%, respectively. The P wave morphology pattern in lead V7 in synthesized 18-lead ECGs is useful for differentiating RIPV origins from RSPV/SVC origins.