Venous congestion and endothelial and neurohormonal activation are known to occur in acute decompensated heart failure (ADHF), yet the temporal role of these processes in the pathophysiology of decompensation is not fully understood. Conventional wisdom presumes congestion to be a consequence of worsening cardiovascular function; however, the biomechanically driven effects of venous congestion are biologically plausible contributors to ADHF that remain largely unexplored in vivo. Recent experimental evidence from human models suggests that fluid accumulation and venous congestion are not simply consequences of poor cardiovascular function, but rather are fundamental pro-oxidant, pro-inflammatory, and hemodynamic stimuli that contribute to acute decompensation. The latest advances in the monitoring of volume status using implantable devices allow for the detection of venous congestion before symptoms arise. This may ultimately lead to improved treatment strategies including not only diuretics, but also specific, adjuvant interventions to counteract endothelial and neurohormonal activation during early preclinical decompensation.

Soluble CD146 is released from the peripheral vasculature in response to venous stretch and may reflect systemic congestion in chronic HF patients.

Endothelin‐1 (ET‐1) is a pivotal mediator of vasoconstriction and inflammation in congestive states such as heart failure (HF) and chronic kidney disease (CKD). Whether peripheral venous congestion (VC) increases plasma ET‐1 at pressures commonly seen in HF and CKD patients is unknown. We seek to characterize whether peripheral VC promotes time‐ and dose‐dependent increases in plasma ET‐1 and whether these changes are sustained after decongestion. We used a randomized, cross‐over design in 20 healthy subjects (age 30 ± 7 years). To experimentally model VC, venous pressure was increased to either 15 or 30 mmHg (randomized at first visit) above baseline by inflating a cuff around the subject's dominant arm; the nondominant arm served as a noncongested control. We measured plasma ET‐1 at baseline, after 20, 60 and 120 min of VC, and finally at 180 min (60 min after cuff release and decongestion). Plasma ET‐1 progressively and significantly increased over 120 min in the congested arm relative to the control arm and to baseline values. This effect was dose‐dependent: ET‐1 increased by 45% and 100% at VC doses of 15 and 30 mmHg, respectively (P < 0.05), and declined after 60 min of decongestion though remaining significantly elevated compared to baseline. In summary, peripheral VC causes time‐ and dose‐dependent increases in plasma ET‐1. Of note, the lower dose of 15 mmHg (more clinically relevant to HF and CKD patients) was sufficient to raise ET‐1. These findings support the potentially contributory, not merely consequential, role of VC in the pathophysiology of HF and CKD.

Introduction: CD146 is a component of the endothelial junction. We previously showed that its soluble form (sCD146) is as powerful as plasma natriuretic peptides to detect cardiac origin of acute dyspnea. The source of plasma sCD146 in heart failure (HF) is however unknown. Hypothesis: We make the hypothesis that peripheral venous congestion (VC), a typical sign of global ventricular failure, might be the source of increased sCD146. Methods: A total of 44 outpatients with heart failure, NYHA functional class II or III, and LVEF <40%, no evidence of VC on physical exam and on stable medical therapy were studied. Patients gave informed consent. To experimentally model VC, venous arm pressure was increased to 30 mmHg above baseline by inflating a pressure cuff around the dominant arm. Blood was sampled from test and control arm (lacking an inflated cuff) before and after 90 minutes of venous congestion. Plasma concentrations of sCD146 were determined by ELISA. Values are expressed as mean ± SEM and groups were compared with paired-samples t-test. Results: The age of the study cohort was 54±2 years, 32% were female, 32% had an ischemic etiology and the LVEF was 22±1%. The induction of VC was associated with an increase in circulating levels of sCD146 in the congested arm when compared to baseline (506±33 vs 463±33 ng/ml, p=0.001) and to control arm (476±32 ng/ml, p=0.035). In contrast, no significant increase occurred in the control arm when compared to baseline values (Figure). Conclusions: Plasma sCD146 acutely increases in response to experimental peripheral VC. sCD146 could be particularly useful to titrate diuretic treatment in HF patients with global heart failure, possibly preventing end-organ dysfunction and damage from severe and/or long-standing peripheral VC.

after development of d-thro (Figure). In particular, we observed a decrease in normalized power of the first and second components, and an increase in normalized power of the third component. Conclusion: Normalized power of the harmonically related first three signal components associated with the HeartMate II rotor show significant alterations before and after thrombosis. This proof of concept analysis suggests that acoustic features can be utilized for non-invasive detection of d-thro.