Using a Fibrinolysis Delivery Catheter in Pulmonary Embolism Treatment for Measurement of Pulmonary Artery Hemodynamics.

Background: Ultrasound-facilitated and catheter-directed low-dose fibrinolysis (EKOS) has shown favorable hemodynamic and safety outcomes in intermediate- to high-risk pulmonary embolism (PE) cases. Objectives: This prospective single-arm monocentric study assessed the effects of using a delivery catheter for fibrinolysis as a novel approach for acute intermediate- to high-risk patients on pulmonary artery hemodynamics PE. Methods: Forty-five patients (41 intermediate−high and 4 high risk) with computer tomography (CT)-confirmed PE underwent EKOS therapy. By protocol, a total of 6 mg of tissue-plasminogen activator (t-PA) was administered over 6 h in the pulmonary artery (unilateral 6 mg or bilateral 12 mg). Unfractionated heparin was provided periprocedurally. The primary safety outcome was death, as well as major and minor bleeding within 48 of procedure initiation and at 90 days. The primary effectiveness outcomes were: 1. to assess the difference in pulmonary artery pressure from baseline to 6 h post-treatment as a primary precise surrogate marker, and 2. to determine the echocardiographic RV/LV ratio from baseline to 48 h and at 90 days post-delivery. Results: Pulmonary artery pressure decreased by 15/6/10 mmHg (p < 0.001). The mean RV/LV ratio decreased from 1.2 ± 0.85 at baseline to 0.85 ± 0.12 at 48 and to 0.76 ± 0.13 at 90 days (p < 0.001). Five patients (11%) died within 90 days of therapy. Conclusions and Highlights: Pulmonary artery hemodynamics were assessed using a delivery catheter for fibrinolysis, which is reproducible for identifying PE at risk of adverse outcomes. The results matched the right heart catheter results in EKOS and Heparin arm of Ultima trial, thereby confirming the validity of this potential diagnostic tool to assess therapy effectiveness and thereby reduce additional procedure-related complications, hospital residency, and economics. These results stress the importance of having an interdisciplinary team involved in the management of PE to evaluate the quality of life of these patients and this protocol shortens ICU admission to 6 h.

Elevation of intracranial pressure affects the relationship between hemoglobin concentration and neuronal activation in human somatosensory cortex.

During neuronal activation, a local decrease of deoxygenated hemoglobin concentration (deoxy-Hb) occurs which is the basis of functional brain imaging with blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI). Elevated intracranial pressure (eICP) has been shown to impair functional deoxy-Hb changes. This study investigated this effect and its relation to the underlying neuronal activity in the human primary somatosensory cortex (SI). Functional near-infrared spectroscopy (fNIRS) during somatosensory evoked potentials (SEP) monitoring was performed on 75 subjects during conditions of median nerve stimulation (MNS) and resting state, combined with normal breathing (NB) and eICP by escalating breathing maneuvers (breath holding [BH], Valsalva maneuver with 15 mmHg [V15] and 35 mmHg expiratory pressure [V35]). During NB, fNIRS revealed a typical oxygenated hemoglobin concentration (oxy-Hb) increase with deoxy-Hb decrease during MNS enabling SI brain mapping. Breathing maneuvers associated eICP produced a known global change of oxy-Hb and deoxy-Hb with and without MNS. When subtracting measurements during resting state from measurements during MNS, neither functional oxy-Hb nor deoxy-Hb changes could be recovered while SEPs remained unchanged. In conclusion, Valsalva-induced eICP prevents oxy-Hb and deoxy-Hb changes during neuronal activation in SI. This finding raises questions on the validity of oxy-Hb- and deoxy-Hb-based brain imaging (e.g., BOLD-fMRI) during eICP.

Valsalva-induced elevation of intracranial pressure selectively decouples deoxygenated hemoglobin concentration from neuronal activation and functional brain imaging capability.

During neuronal activation, neurovascular coupling leads to a local decrease of deoxygenated hemoglobin concentration (deoxy-Hb) and thus forms the basis of many functional brain mapping methods. In animals, an elevated intracranial pressure (ICP) can attenuate or even reverse this deoxy-Hb signaling. To study the effect of an elevated ICP on functional brain imaging in humans, we used different breathing tasks to modify ICP and analyzed the resulting effect on neurovascular coupling in the motor cortex. Functional near-infrared spectroscopy (fNIRS) was performed on 45 subjects during alternating conditions of finger tapping and resting state combined with four different breathing maneuvers (normal breathing (NB), breath holding without Valsalva maneuver (BH), Valsalva maneuver with 15 mm Hg forced expiratory pressure against resistance (V15) and Valsalva maneuver with 35 mm Hg forced expiratory pressure against resistance (V35)) in randomized order. With escalation of breathing tasks the median amplitude of the functional deoxy-Hb decrease during finger tapping became smaller. In contrast, functional oxygenated hemoglobin concentration (oxy-Hb) and total hemoglobin concentration (total-Hb) responses did not show a significant alteration. The functional oxy-Hb map evoked by finger tapping withstood Valsalva challenges while the functional deoxy-Hb map identified the correct motor cortex in normal breathing conditions only and did not reveal a functional contrast during Valsalva maneuvers. In summary, we conclude that during ICP elevation, deoxy-Hb is not a reliable basis for functional brain imaging. This suggests that the validity of BOLD fMRI during increased ICP might be impaired.