Multiparameter diagnostic sensor measurements in heart failure patients presenting with SARS‐CoV‐2 infection

Aims: Implantable device‐based sensor measurements including heart sounds, markers of ventilation, and thoracic impedance have been shown to predict heart failure (HF) hospitalizations. We sought to assess how these parameters changed prior to COVID‐19 (Cov‐19) and how these compared with those presenting with decompensated HF or pneumonia. Methods and results: This retrospective analysis explores patterns of changes in daily measurements by implantable sensors in 10 patients with Cov‐19 and compares these findings with those observed prior to HF (n = 88) and pneumonia (n = 12) hospitalizations from the MultiSENSE, PREEMPT‐HF, and MANAGE‐HF trials. The earliest sensor changes prior to Cov‐19 were observed in respiratory rate (6 days) and temperature (5 days). There was a three‐fold to four‐fold greater increase in respiratory rate, rapid shallow breathing index, and night heart rate compared with those presenting with HF or pneumonia. Furthermore, activity levels fell more in those presenting with Cov‐19, a change that was often sustained for some time. In contrast, there were no significant changes in 1st or 3rd heart sound (S1 and S3) amplitude in those presenting with Cov‐19 or pneumonia compared with the known changes that occur in HF decompensation. Conclusions: Multi‐sensor device diagnostics may provide early detection of Cov‐19, distinguishable from worsening HF by an extreme and fast rise in respiratory rate along with no changes in S3

PRecision Event Monitoring for PatienTs with Heart Failure using HeartLogic (PREEMPT‐HF) study design and enrolment

Abstract Aims The HeartLogic multisensor index has been found to be a sensitive predictor of worsening heart failure (HF). However, there is limited data on this index's association and its constituent sensors with HF readmissions. Methods and results The PREEMPT‐HF study is a global, multicentre, prospective, observational, single‐arm, post‐market study. HF patients with an implantable defibrillator device or cardiac resynchronization therapy with defibrillator with HeartLogic capabilities were eligible if sensor data collection was turned on and the HeartLogic feature was not enabled. Thus, the HeartLogic Index/alert and heart sounds sensor trends were unavailable via the LATITUDE remote monitoring system to clinicians (blinded). Evaluation of subject medical records at 6 months and a final in‐clinic visit at 12 months was required for collection of all‐cause hospitalizations and HF outpatient visits. The purpose of this study is exploratory, no formal hypothesis tests are planned, and no adjustment for multiple testing will be performed. A total of 2183 patients were enrolled at 103 sites between June 2018 and June 2020. A significant proportion of the patients were implanted with implantable defibrillator devices (39%) versus cardiac resynchronization therapy with defibrillator (61%); were female (27%); over 65 (61%); New York Heart Association class I (13%), II (53%), and III (33%); ejection fraction < 25% (21%); ischaemic (50%); and with a history of renal dysfunction (23%). Conclusions The PREEMPT study will provide clinical data and blinded sensor trends for the characterization of sensor changes with HF readmission, tachyarrhythmias, and event subgroups. These data may help to refine the clinical use of HeartLogic and to improve patient outcomes

Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 deficiency reduces leukocyte infiltration into adipose tissue and favors fat deposition

1525-2191 (Electronic) Journal ArticleObesity is associated with low-grade inflammation and leukocyte infiltration in white adipose tissue (WAT) and is linked to diabetic complications. Semicarbazide-sensitive amine oxidase, also known as vascular adhesion protein-1 (SSAO/VAP-1), is a membrane protein that is highly expressed in adipocytes and is also present on the endothelial cell surface where it is involved in leukocyte extravasation. We studied fat deposition and leukocyte infiltration in WAT of mice with a null mutation in the amine oxidase copper-containing-3 (AOC3) gene encoding SSAO/VAP-1. Both epididymal and inguinal WATs were larger in 6-month-old AOC3-KO males than in age-matched wild-type controls. However, WAT from AOC3-KO mice contained lower CD45 mRNA levels and fewer CD45(+) leukocytes. Subpopulation analyses revealed a diminished infiltration of WAT by T cells, macrophages, natural killer, and natural killer T cells. A decrease in leukocyte content in WAT was also detected in female AOC3-KO mice as early as 2 months of age, whereas increased fat mass was evident by 6 months of age. Reduced CD45(+) populations in WAT of AOC3-KO mice was not rescued by human SSAO/VAP-1 expression on adipocytes under the control of aP2, suggesting the importance of vascular AOC3 in leukocyte entrance into fat. Our results indicate that SSAO/VAP-1 is instrumental for the presence of leukocytes in WAT. Therefore, AOC3-KO mice present a unique model of mild obesity, characterized by increased WAT devoid of low-grade inflammation

Chronic vagal stimulation for the treatment of low ejection fraction heart failure : results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial

AIM: The neural cardiac therapy for heart failure (NECTAR-HF) was a randomized sham-controlled trial designed to evaluate whether a single dose of vagal nerve stimulation (VNS) would attenuate cardiac remodelling, improve cardiac function and increase exercise capacity in symptomatic heart failure patients with severe left ventricular (LV) systolic dysfunction despite guideline recommended medical therapy. METHODS: Patients were randomized in a 2 : 1 ratio to receive therapy (VNS ON) or control (VNS OFF) for a 6-month period. The primary endpoint was the change in LV end systolic diameter (LVESD) at 6 months for control vs. therapy, with secondary endpoints of other echocardiography measurements, exercise capacity, quality-of-life assessments, 24-h Holter, and circulating biomarkers. RESULTS: Of the 96 implanted patients, 87 had paired datasets for the primary endpoint. Change in LVESD from baseline to 6 months was -0.04 ± 0.25 cm in the therapy group compared with -0.08 ± 0.32 cm in the control group (P = 0.60). Additional echocardiographic parameters of LV end diastolic dimension, LV end systolic volume, left ventricular end diastolic volume, LV ejection fraction, peak V02, and N-terminal pro-hormone brain natriuretic peptide failed to show superiority compared to the control group. However, there were statistically significant improvements in quality of life for the Minnesota Living with Heart Failure Questionnaire (P = 0.049), New York Heart Association class (P = 0.032), and the SF-36 Physical Component (P = 0.016) in the therapy group. CONCLUSION: Vagal nerve stimulation as delivered in the NECTAR-HF trial failed to demonstrate a significant effect on primary and secondary endpoint measures of cardiac remodelling and functional capacity in symptomatic heart failure patients, but quality-of-life measures showed significant improvement