Continuous assessment of ventricular fibrillation prognostic status during CPR: Implications for resuscitation.

BACKGROUND: Ventricular fibrillation (VF) waveform measures reflect myocardial physiologic status. Continuous assessment of VF prognosis using such measures could guide resuscitation, but has not been possible due to CPR artifact in the ECG. A recently-validated VF measure (termed VitalityScore), which estimates the probability (0-100%) of return-of-rhythm (ROR) after shock, can assess VF during CPR, suggesting potential for continuous application during resuscitation. OBJECTIVE: We evaluated VF using VitalityScore to characterize VF prognostic status continuously during resuscitation. METHODS: We characterized VF using VitalityScore during 60 seconds of CPR and 10 seconds of subsequent pre-shock CPR interruption in patients with out-of-hospital VF arrest. VitalityScore utility was quantified using area under the receiver operating characteristic curve (AUC). VitalityScore trends over time were estimated using mixed-effects models, and associations between trends and ROR were evaluated using logistic models. A sensitivity analysis characterized VF during protracted (100-second) periods of CPR. RESULTS: We evaluated 724 VF episodes among 434 patients. After an initial decline from 0-8 seconds following VF onset, VitalityScore increased slightly during CPR from 8-60 seconds (slope: 0.18%/min). During the first 10 seconds of subsequent pre-shock CPR interruption, VitalityScore declined (slope: -14%/min). VitalityScore predicted ROR throughout CPR with AUCs 0.73-0.75. Individual VitalityScore trends during 8-60 seconds of CPR were marginally associated with subsequent ROR (adjusted odds ratio for interquartile slope change (OR) = 1.10, p = 0.21), and became significant with protracted (100 seconds) CPR duration (OR = 1.28, p = 0.006). CONCLUSION: VF prognostic status can be continuously evaluated during resuscitation, a development that could translate to patient-specific resuscitation strategies.

Investigating the Airway Opening Index during cardiopulmonary resuscitation.

INTRODUCTION: Chest compressions during CPR induce oscillations in capnography (ETCO2) waveforms. Studies suggest ETCO2 oscillation characteristics are associated with intrathoracic airflow dependent on airway patency. Oscillations can be quantified by the Airway Opening Index (AOI). We sought to evaluate multiple methods of computing AOI and their association with return of spontaneous circulation (ROSC). METHODS: We conducted a retrospective study of 307 out-of-hospital cardiac arrest (OHCA) cases in Seattle, WA during 2019. ETCO2 and chest impedance waveforms were annotated for the presence of intubation and CPR. We developed four methods for computing AOI based on peak ETCO2 and the oscillations in ETCO2 during chest compressions (ΔETCO2). We examined the feasibility of automating ΔETCO2 and AOI calculation and evaluated differences in AOI across the methods using nonparametric testing (α = 0.05). RESULTS: Median [interquartile range] AOI across all cases using Methods 1-4 was 28.0 % [17.9-45.5 %], 20.6 % [13.0-36.6 %], 18.3 % [11.4-30.4 %], and 22.4 % [12.8-38.5 %], respectively (p < 0.001). Cases with ROSC had a higher median AOI than those without ROSC across all methods, though not statistically significant. Cases with ROSC had a significantly higher median [interquartile range] ΔETCO2 of 7.3 mmHg [4.5-13.6 mmHg] compared to those without ROSC (4.8 mmHg [2.6-9.1 mmHg], p < 0.001). CONCLUSION: We calculated AOI using four proposed methods resulting in significantly different AOI. Additionally, AOI and ΔETCO2 were larger in cases achieving ROSC. Further investigation is required to characterize AOI's ability to predict OHCA outcomes, and whether this information can improve resuscitation care.

Machine learning and feature engineering for predicting pulse presence during chest compressions.

Current resuscitation protocols require pausing chest compressions during cardiopulmonary resuscitation (CPR) to check for a pulse. However, pausing CPR when a patient is pulseless can worsen patient outcomes. Our objective was to design and evaluate an ECG-based algorithm that predicts pulse presence with or without CPR. We evaluated 383 patients being treated for out-of-hospital cardiac arrest with real-time ECG, impedance and audio recordings. Paired ECG segments having an organized rhythm immediately preceding a pulse check (during CPR) and during the pulse check (without CPR) were extracted. Patients were randomly divided into 60% training and 40% test groups. From training data, we developed an algorithm to predict the clinical pulse presence based on the wavelet transform of the bandpass-filtered ECG. Principal component analysis was used to reduce dimensionality, and we then trained a linear discriminant model using three principal component modes as input features. Overall, 38% (351/912) of checks had a spontaneous pulse. AUCs for predicting pulse presence with and without CPR on test data were 0.84 (95% CI (0.80, 0.88)) and 0.89 (95% CI (0.86, 0.92)), respectively. This ECG-based algorithm demonstrates potential to improve resuscitation by predicting the presence of a spontaneous pulse without pausing CPR with moderate accuracy.

Electrocardiogram-based pulse prediction during cardiopulmonary resuscitation.

OBJECTIVE: Resuscitation requires CPR interruptions every 2 min to assess rhythm and pulse status. We developed a method to predict real-time pulse status in organized rhythm ECG segments with and without CPR artifact. METHODS: The study cohort included patients who received attempted resuscitation following ventricular fibrillation arrest. Using audio-supplemented defibrillator recordings, we annotated CPR, rhythm, and pulse status at each two-minute rhythm/pulse check. Paired ECG segments with and without CPR were extracted at each rhythm/pulse check. Using one-third of cases for training and two-thirds for validation, we developed three wavelet-based ECG features and combined them with a logistic model to predict pulse status. Predictive performances of each individual ECG feature and the combined logistic model were measured by the area under the receiver operator characteristic curve (AUC) in the validation cases with and without CPR. RESULTS: There were 238 cases and 911 ECG segment pairs. Among 319 organized rhythm segments in the validation set, AUC for pulse prediction during CPR ranged from 0.67 to 0.79 for the individual ECG features. The logistic model was more predictive than any individual feature (AUC 0.84, 95% CI 0.80-0.89, p < 0.05 for each comparison) and performed similarly regardless of CPR (p = 0.2 for difference). CONCLUSION: ECG features extracted by wavelet analysis predicted pulse status with moderate accuracy among organized rhythm segments with and without CPR. Further study is required to understand how real-time pulse prediction during CPR could help direct care while limiting CPR interruption.

Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration.

The epicardium and its derivatives provide trophic and structural support for the developing and adult heart. Here we tested the ability of human embryonic stem cell (hESC)-derived epicardium to augment the structure and function of engineered heart tissue in vitro and to improve efficacy of hESC-cardiomyocyte grafts in infarcted athymic rat hearts. Epicardial cells markedly enhanced the contractility, myofibril structure and calcium handling of human engineered heart tissues, while reducing passive stiffness compared with mesenchymal stromal cells. Transplanted epicardial cells formed persistent fibroblast grafts in infarcted hearts. Cotransplantation of hESC-derived epicardial cells and cardiomyocytes doubled graft cardiomyocyte proliferation rates in vivo, resulting in 2.6-fold greater cardiac graft size and simultaneously augmenting graft and host vascularization. Notably, cotransplantation improved systolic function compared with hearts receiving either cardiomyocytes alone, epicardial cells alone or vehicle. The ability of epicardial cells to enhance cardiac graft size and function makes them a promising adjuvant therapeutic for cardiac repair.

Afterload promotes maturation of human induced pluripotent stem cell derived cardiomyocytes in engineered heart tissues.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) grown in engineered heart tissue (EHT) can be used for drug screening, disease modeling, and heart repair. However, the immaturity of hiPSC-CMs currently limits their use. Because mechanical loading increases during development and facilitates cardiac maturation, we hypothesized that afterload would promote maturation of EHTs. To test this we developed a system in which EHTs are suspended between a rigid post and a flexible one, whose resistance to contraction can be modulated by applying braces of varying length. These braces allow us to adjust afterload conditions over two orders of magnitude by increasing the flexible post resistance from 0.09 up to 9.2 µN/µm. After three weeks in culture, optical tracking of post deflections revealed that auxotonic twitch forces increased in correlation with the degree of afterload, whereas twitch velocities decreased with afterload. Consequently, the power and work of the EHTs were maximal under intermediate afterloads. When studied isometrically, the inotropy of EHTs increased with afterload up to an intermediate resistance (0.45 µN/µm) and then plateaued. Applied afterload increased sarcomere length, cardiomyocyte area and elongation, which are hallmarks of maturation. Furthermore, progressively increasing the level of afterload led to improved calcium handling, increased expression of several key markers of cardiac maturation, including a shift from fetal to adult ventricular myosin heavy chain isoforms. However, at the highest afterload condition, markers of pathological hypertrophy and fibrosis were also upregulated, although the bulk tissue stiffness remained the same for all levels of applied afterload tested. Together, our results indicate that application of moderate afterloads can substantially improve the maturation of hiPSC-CMs in EHTs, while high afterload conditions may mimic certain aspects of human cardiac pathology resulting from elevated mechanical overload.

Rhythm profiles and survival after out-of-hospital ventricular fibrillation cardiac arrest.

OBJECTIVE: Treatment: protocols for cardiac arrest rely upon rhythm analyses performed at two-minute intervals, neglecting possible rhythm changes during the intervening period of CPR. Our objective was to describe rhythm profiles (patterns of rhythm transitions during two-minute CPR cycles) following attempted defibrillation and to assess their relationship to survival. METHODS: The study included out-of-hospital cardiac arrest cases presenting with ventricular fibrillation from 2011 to 2015. The rhythm sequence was annotated during two-minute CPR cycles after the first and second shocks of each case, and the rhythm profile of each sequence was classified. We calculated absolute survival differences among rhythm profiles with the same rhythm at the two-minute check. RESULTS: Of 569 rhythm sequences after the first shock, 46% included a rhythm transition. Overall survival was 47%, and survival proportion varied by rhythm at the two-minute check: ventricular fibrillation (46%), organized (58%) and asystole (20%). Survival was similar between profiles which ended with an organized rhythm at the two-minute check. Likewise, survival was similar between profiles with asystole at the two-minute check. However, in patients with ventricular fibrillation at the two-minute check, survival was twice as high in those with a transient organized rhythm (69%) compared to constant ventricular fibrillation (32%) or transient asystole (28%). CONCLUSION: Rhythm transitions are common after attempted defibrillation. Among patients with ventricular fibrillation at the subsequent two-minute check, transient organized rhythm during the preceding two-minute CPR cycle was associated with favorable survival, suggesting distinct physiologies that could serve as the basis for different treatment strategies.

Detection of Anterior Circulation Large Artery Occlusion in Ischemic Stroke Using Noninvasive Cerebral Oximetry.

BACKGROUND AND PURPOSE: Large artery occlusion (LAO) in ischemic stroke requires recognition and triage to an endovascular stroke treatment center. Noninvasive LAO detection is needed to improve triage. METHODS: Prospective study to test whether noninvasive cerebral oximetry can detect anterior circulation LAO in acute stroke. Interhemispheric ΔBrSO2 in LAO was compared with controls. RESULTS: In LAO stroke, mean interhemispheric ΔBrSO2 was -8.3±5.8% (n=19), compared with 0.4±5.8% in small artery stroke (n=17), 0.4±6.0% in hemorrhagic stroke (n=14), and 0.2±7.5% in subjects without stroke (n=19) (P<0.001). Endovascular stroke treatment reduced the ΔBrSO2 in most LAO subjects (16/19). Discrimination of LAO at a -3% ΔBrSO2 cut had 84% sensitivity and 70% specificity. Addition of the G-FAST clinical score (gaze-face-arm-speech- time) to the BrSO2 measure had 84% sensitivity and 90% specificity. CONCLUSIONS: Noninvasive cerebral oximetry may help detect LAO in ischemic stroke, particularly when combined with a simple clinical scoring system.

Real-Time Force and Frequency Analysis of Engineered Human Heart Tissue Derived from Induced Pluripotent Stem Cells Using Magnetic Sensing.

Engineered heart tissues made from human pluripotent stem cell-derived cardiomyocytes have been used for modeling cardiac pathologies, screening new therapeutics, and providing replacement cardiac tissue. Current methods measure the functional performance of engineered heart tissue by their twitch force and beating frequency, typically obtained by optical measurements. In this article, we describe a novel method for assessing twitch force and beating frequency of engineered heart tissue using magnetic field sensing, which enables multiple tissues to be measured simultaneously. The tissues are formed as thin structures suspended between two silicone posts, where one post is rigid and another is flexible and contains an embedded magnet. When the tissue contracts it causes the flexible post to bend in proportion to its twitch force. We measured the bending of the post using giant magnetoresistive (GMR) sensors located underneath a 24-well plate containing the tissues. We validated the accuracy of the readings from the GMR sensors against optical measurements. We demonstrated the utility and sensitivity of our approach by testing the effects of three concentrations of isoproterenol and verapamil on twitch force and beating frequency in real-time, parallel experiments. This system should be scalable beyond the 24-well format, enabling greater automation in assessing the contractile function of cardiomyocytes in a tissue-engineered environment.