First-in-Human Study to Assess the Safety and Feasibility of the Bashir Endovascular Catheter for the Treatment of Acute Intermediate-Risk Pulmonary Embolism

Background: The Bashir Endovascular Catheter (BEC) is a novel pharmaco-mechanical device designed to enhance thrombolysis by increasing the exposure of thrombus to endogenous and exogenous thrombolytics. The aim of this prospective, multicenter, single-arm study was to evaluate the feasibility and initial safety of the BEC in patients with acute intermediate-risk pulmonary embolism (PE). Methods: Patients with symptomatic PE and right ventricular to left ventricular diameter ratio ≥0.9 as documented by computer tomography angiography were eligible for enrollment. The primary safety end points were device related death or adverse events, and major bleeding within 72 hours after BEC directed therapy. Results: Nine patients were enrolled across 4 US sites. The total dose of r-tPA (recombinant tissue-type plasminogen activator) was 14 mgs in bilateral PE and 12 mgs in unilateral PE over 8 hours delivered via the expanded BEC. At 30-day follow-up, there were no deaths or device-related adverse events. At 48 hours post-BEC therapy, the right ventricular to left ventricular diameter ratio decreased from 1.52±0.26 to 0.97±0.06 ( P =0.0009 [95% CI, 0.33–0.82]; 37.0% reduction). Thrombus burden as measured by the Modified Miller Index decreased from 25.4±5.3 to 16.0±4.0 ( P =0.0005; [95% CI, 5.5–13.4]; 37.1% reduction). Conclusions: In this early feasibility study of the BEC for intermediate-risk PE, there were no deaths or device-related adverse events and a significant reduction in right ventricular to left ventricular diameter ratio and thrombus burden. REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03927508.

One-Year Echocardiographic, Functional, and Quality of Life Outcomes After Ultrasound-Facilitated Catheter-Based Fibrinolysis for Pulmonary Embolism

Background: Accelerated tPA (tissue-type plasminogen activator) dosing regimens for ultrasound-facilitated, catheter-directed fibrinolysis improve short-term computed tomographic-measured right ventricular (RV)-to-left ventricular diameter ratio in massive and submassive pulmonary embolism. The impact on RV remodeling, functional status, and quality of life over the long-term remains unclear. Methods: To study 1-year changes in RV remodeling, functional status, and quality of life, we assessed patients with acute submassive pulmonary embolism randomly assigned to 1 of 4 tPA dosing regimens for ultrasound-facilitated, catheter-directed fibrinolysis in the OPTALYSE-PE trial (Optimum Duration and Dose of r-tPA With the Acoustic Pulse Thrombolysis Procedure for Intermediate-Risk Pulmonary Embolism; 8 mg/2 hours, 8 mg/4 hours, 12 mg/6 hours, and 24 mg/6 hours). Echocardiographic assessment included RV-to-left ventricular diameter ratio within 4 hours of treatment end, and at 48 hours, 30 days, 90 days, and 1 year. Functional status was assessed by 6-minute walk test at 30 days, 90 days, and 1 year and PROMIS-PF-6b scores at 30 days, 90 days, 180 days, 270 days, and 1 year. Quality of life was evaluated by PEmb-QOL scores at 30 days, 90 days, 180 days, 270 days, and 1 year. Results: Mean RV-to-left ventricular diameter ratio decreased from baseline to 4 hours and further at 48 hours and 30 days, with reductions maintained at 90 days and 1 year in all groups. Mean 6-minute walk distance, PROMIS-PF-6b, and PEmb-QOL scores improved over the course of 1 year in all groups. Conclusions: Accelerated lower-dose tPA regimens for ultrasound-facilitated, catheter-directed fibrinolysis resulted in sustained recovery of RV-to-left ventricular diameter ratio and tricuspid annular plane systolic excursion and improvements in functional status and quality of life over 1 year. Registration: URL: https://www.ClinicalTrials.gov . Unique Identifier: NCT02396758.

Trajectory analysis of cardiovascular phenotypes from biobank data uncovers novel genetic associations

ABSTRACTApproximately 6 million adults in the US have heart failure (HF). HF progression is variable due in part to differences in sex, age, and genetic ancestry. Previous population-based genetic studies have largely focused on cross-sectional data related to HF, a disease known to change over time. Utilizing longitudinal data trajectory probabilities as a continuous trait may increase the likelihood of finding significant, biologically relevant associations in a genome-wide association (GWA) analysis. We analyzed data from the electronic health record in a medical biobank from a single, metropolitan US center to gather clinically pertinent data for analyses. We evaluated whole genome sequencing of 896 unrelated biobank participants, including 494 with at least 1 electrocardiogram and 324 who had more than 1 echocardiogram (∼3 observations per person). A censored normal distribution multivariable mixture model was used to cluster phenotype measures for genome-wide analyses. GWA analysis on the trajectory probability of the corrected QT measurement (QTc) taken from electrocardiograms identified significant associations with variants in regulatory regions proximal to the WLS gene, which encodes the Wnt ligand secretion mediator, Wntless. WLS was previously associated with QT length using of approximately 16,000 participants supporting the utility of this method to uncover significant genetic associations in small datasets. GWA analysis on the trajectory probability of left ventricular diameter as taken from echocardiograms identified novel significant associations with variants in regulatory regions near MYO10, which encodes the unconventional Myosin-10. We found that trajectory probabilities improved the ability to discover significant and relevant genetic associations. This novel approach increased yield from smaller, well-phenotyped cohorts with longitudinal data from a medical biobank.AUTHOR SUMMARYApproximately 6 million adults in the US have heart failure, a disease known to change over time. In a hospital based electronic health record, electrocardiograms and echocardiograms, used to evaluate heart failure, can be tracked over time. We utilized these data to create a novel trait that can be applied to genetic analyses. We analyzed genome sequence of 896 biobank participants from diverse racial/ethnic backgrounds. Genome-wide association (GWA) analyses were performed on a subset of these individuals for heart failure outcomes. A statistical model that incorporates cardiac data that are tracked over time was used to cluster these data using a probabilistic approach. These probabilities were used for a GWA analysis for corrected QT measurement (QTc) and left ventricular diameter (LVID). The QTc interval analysis identified significant correlations with variants in regulatory regions near the WLS gene which encodes the Wnt ligand secretion mediator, Wntless. Analysis of LVID identified significant associations with variants in regulatory regions near the MYO10 gene which encodes the unconventional Myosin-10. Through these analyses, we found that using the trajectory probabilities can facilitate the discovery of novel significant, biologically relevant associations. This method reduces the need for larger cohorts, and increases yield from smaller, well-phenotyped cohorts.

The optimal chest compression point on sternum based on chest-computed tomography: A retrospective study

Background: High-quality chest compression is crucial for cardiac arrest patients. However, only few studies are focusing on the optimal compression point. Objective: The aim of this study was to explore the optimal compression point based on chest-computed tomography. Methods: We retrospectively selected 166 adult health subjects between January 2018 and May 2018 in a university-affiliated hospital. Results: The median length of sternum was 14.9 cm. The median length from the inter-nipple line to the distal end of sternum was 1.0 cm. The median length from the point at which the maximal left ventricular diameter projected onto the sternum to the distal end of the sternum was −1.4 (–2.2 to 0.0) cm. The median value of the length from the inter-nipple line to the distal end of sternum plus the length from the point at which the maximal left ventricular diameter projected onto the sternum to the distal end of the sternum was 2.0 (1.0–3.1) cm. Conclusion: One size does not fit all. The point recommended by the current guideline may not appropriate for Chinese person. Further studies are required focusing on individual chest compression during cardiopulmonary resuscitation.

Echocardiographic parameters in dogs treated with acepromazine and fentanyl

ABSTRACT Considering that the use of tranquillizers could optimize the performance of the echocardiogram, this study aimed to evaluate the effect of protocols with acepromazine and fentanyl on the echocardiographic parameters of healthy dogs, besides their effect in systolic blood pressure (SBP), respiratory rate (RR), heart rate (HR), time spent for examination and sedation scale. Ten adult dogs were submitted to different tranquilizing protocols 20 minutes before the echocardiographic examination, totalling five treatments for each pair, performed at seven-day intervals between evaluations. The treatments were CT (control treatment), IAT (intramuscular acepromazine), OAT (oral acepromazine), FT (fentanyl) and AFT (acepromazine associated with fentanyl). In addition to the echocardiographic evaluation, SBP, degree of reassurance, duration of the exam, HR and RR in the different protocols were evaluated. There was a significant decrease of SBP in OAT. There was a significant reduction in left ventricular diameter during systole and diastole and mitral annular movement in IAT, OAT and AFT, compared with CT. There was a decrease in tricuspid annular plane systolic excursion and increase in mitral E/mitral A ratio in IAT and OAT when compared with CT. All the tranquillizer protocols studied were found to significantly reduce HR, that facilitated the echocardiographic examination.