Effect of intra-arrest transport, extracorporeal cardiopulmonary resuscitation and immediate invasive assessment in refractory out-of-hospital cardiac arrest: a long-term follow-up of the Prague OHCA trial.

BACKGROUND: Randomized data evaluating the impact of the extracorporeal cardiopulmonary resuscitation (ECPR) approach on long-term clinical outcomes in patients with refractory out-of-hospital cardiac arrest (OHCA) are lacking. The objective of this follow-up study was to assess the long-term clinical outcomes of the ECPR-based versus CCPR approach. METHODS: The Prague OHCA trial was a single-center, randomized, open-label trial. Patients with witnessed refractory OHCA of presumed cardiac origin, without return of spontaneous circulation, were randomized during ongoing resuscitation on scene to conventional CPR (CCPR) or an ECPR-based approach (intra-arrest transport, ECPR if ROSC is not achieved prehospital and immediate invasive assessment). RESULTS: From March 2013 to October 2020, 264 patients were randomized during ongoing resuscitation on scene, and 256 patients were enrolled. Long-term follow-up was performed 5.3 (interquartile range 3.8-7.2) years after initial randomization and was completed in 255 of 256 patients (99.6%). In total, 34/123 (27.6%) patients in the ECPR-based group and 26/132 (19.7%) in the CCPR group were alive (log-rank P = 0.01). There were no significant differences between the treatment groups in the neurological outcome, survival after hospital discharge, risk of hospitalization, major cardiovascular events and quality of life. Of long-term survivors, 1/34 (2.9%) in the ECPR-based arm and 1/26 (3.8%) in the CCPR arm had poor neurological outcome (both patients had a cerebral performance category score of 3). CONCLUSIONS: Among patients with refractory OHCA, the ECPR-based approach significantly improved long-term survival. There were no differences in the neurological outcome, major cardiovascular events and quality of life between the groups, but the trial was possibly underpowered to detect a clinically relevant difference in these outcomes. Trial registration ClinicalTrials.gov Identifier: NCT01511666, Registered 19 January 2012.

Fractional Flow Reserve Versus Instantaneous Wave-Free Ratio in Assessment of Lesion Hemodynamic Significance and Explanation of their Discrepancies. International, Multicenter and Prospective Trial: The FiGARO Study.

Background The FiGARO (FFR versus iFR in Assessment of Hemodynamic Lesion Significance, and an Explanation of Their Discrepancies) trial is a prospective registry searching for predictors of fractional flow reserve/instantaneous wave-free ratio (FFR/iFR) discrepancy. Methods and Results FFR/iFR were analyzed using a Verrata wire, and coronary flow reserve was analyzed using a Combomap machine (both Philips-Volcano). The risk polymorphisms for endothelial nitric oxide synthase and for heme oxygenase-1 were analyzed. In total, 1884 FFR/iFR measurements from 1564 patients were included. The FFR/iFR discrepancy occurred in 393 measurements (20.9%): FFRp (positive)/iFRn (negative) type (264 lesions, 14.0%) and FFRn/iFRp (129 lesions, 6.8%) type. Coronary flow reserve was measured in 343 lesions, correlating better with iFR (R=0.56, P<0.0001) than FFR (R=0.36, P<0.0001). The coronary flow reserve value in FFRp/iFRn lesions (2.24±0.7) was significantly higher compared with both FFRp/iFRp (1.39±0.36), and FFRn/iFRn lesions (1.8±0.64, P<0.0001). Multivariable logistic regression analysis confirmed (1) sex, age, and lesion location in the right coronary artery as predictors for FFRp/iFRn discrepancy; and (2) hemoglobin level, smoking, and renal insufficiency as predictors for FFRn/iFRp discrepancy. The FFRn/iFRp type of discrepancy was significantly more frequent in patients with both risk types of polymorphisms (endothelial nitric oxide synthaser+heme oxygenase-1r): 8 patients (24.2%) compared with FFRp/iFRn type of discrepancy: 2 patients (5.9%), P=0.03. Conclusions Predictors for FFRp/iFRn discrepancy were sex, age, and location in the right coronary artery. Predictors for FFRn/iFRp were hemoglobin level, smoking, and renal insufficiency. The risk type of polymorphism in endothelial nitric oxide synthase and heme oxygenase-1 genes was more frequently found in patients with FFRn/iFRp type of discrepancy. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT03033810.

Effect of Intra-arrest Transport, Extracorporeal Cardiopulmonary Resuscitation, and Immediate Invasive Assessment and Treatment on Functional Neurologic Outcome in Refractory Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: Out-of-hospital cardiac arrest (OHCA) has poor outcome. Whether intra-arrest transport, extracorporeal cardiopulmonary resuscitation (ECPR), and immediate invasive assessment and treatment (invasive strategy) is beneficial in this setting remains uncertain. Objective: To determine whether an early invasive approach in adults with refractory OHCA improves neurologically favorable survival. Design, Setting, and Participants: Single-center, randomized clinical trial in Prague, Czech Republic, of adults with a witnessed OHCA of presumed cardiac origin without return of spontaneous circulation. A total of 256 participants, of a planned sample size of 285, were enrolled between March 2013 and October 2020. Patients were observed until death or day 180 (last patient follow-up ended on March 30, 2021). Interventions: In the invasive strategy group (n = 124), mechanical compression was initiated, followed by intra-arrest transport to a cardiac center for ECPR and immediate invasive assessment and treatment. Regular advanced cardiac life support was continued on-site in the standard strategy group (n = 132). Main Outcomes and Measures: The primary outcome was survival with a good neurologic outcome (defined as Cerebral Performance Category [CPC] 1-2) at 180 days after randomization. Secondary outcomes included neurologic recovery at 30 days (defined as CPC 1-2 at any time within the first 30 days) and cardiac recovery at 30 days (defined as no need for pharmacological or mechanical cardiac support for at least 24 hours). Results: The trial was stopped at the recommendation of the data and safety monitoring board when prespecified criteria for futility were met. Among 256 patients (median age, 58 years; 44 [17%] women), 256 (100%) completed the trial. In the main analysis, 39 patients (31.5%) in the invasive strategy group and 29 (22.0%) in the standard strategy group survived to 180 days with good neurologic outcome (odds ratio [OR], 1.63 [95% CI, 0.93 to 2.85]; difference, 9.5% [95% CI, -1.3% to 20.1%]; P = .09). At 30 days, neurologic recovery had occurred in 38 patients (30.6%) in the invasive strategy group and in 24 (18.2%) in the standard strategy group (OR, 1.99 [95% CI, 1.11 to 3.57]; difference, 12.4% [95% CI, 1.9% to 22.7%]; P = .02), and cardiac recovery had occurred in 54 (43.5%) and 45 (34.1%) patients, respectively (OR, 1.49 [95% CI, 0.91 to 2.47]; difference, 9.4% [95% CI, -2.5% to 21%]; P = .12). Bleeding occurred more frequently in the invasive strategy vs standard strategy group (31% vs 15%, respectively). Conclusions and Relevance: Among patients with refractory out-of-hospital cardiac arrest, the bundle of early intra-arrest transport, ECPR, and invasive assessment and treatment did not significantly improve survival with neurologically favorable outcome at 180 days compared with standard resuscitation. However, the trial was possibly underpowered to detect a clinically relevant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT01511666.

Assessment of Asymptomatic Severe Aortic Regurgitation by Doppler-Derived Echo Indices: Comparison with Magnetic Resonance Quantification.

Reliable quantification of aortic regurgitation (AR) severity is essential for clinical management. We aimed to compare quantitative and indirect echo-Doppler indices to quantitative cardiac magnetic resonance (CMR) parameters in asymptomatic chronic severe AR. Methods and Results: We evaluated 104 consecutive patients using echocardiography and CMR. A comprehensive 2D, 3D, and Doppler echocardiography was performed. The CMR was used to quantify regurgitation fraction (RF) and volume (RV) using the phase-contrast velocity mapping technique. Concordant grading of AR severity with both techniques was observed in 77 (74%) patients. Correlation between RV and RF as assessed by echocardiography and CMR was relatively good (rs = 0.50 for RV, rs = 0.40 for RF, p < 0.0001). The best correlation between indirect echo-Doppler and CMR parameters was found for diastolic flow reversal (DFR) velocity in descending aorta (rs = 0.62 for RV, rs = 0.50 for RF, p < 0.0001) and 3D vena contracta area (VCA) (rs = 0.48 for RV, rs = 0.38 for RF, p < 0.0001). Using receiver operating characteristic analysis, the largest area under curve (AUC) to predict severe AR by CMR RV was observed for DFR velocity (AUC = 0.79). DFR velocity of 19.5 cm/s provided 78% sensitivity and 80% specificity. The AUC for 3D VCA to predict severe AR by CMR RV was 0.73, with optimal cut-off of 26 mm2 (sensitivity 80% and specificity 66%). Conclusions: Out of the indirect echo-Doppler indices of AR severity, DFR velocity in descending aorta and 3D vena contracta area showed the best correlation with CMR-derived RV and RF in patients with chronic severe AR.

Validation of new marker of fluid responsiveness based on Doppler assessment of blood flow velocity in superior vena cava in mechanically ventilated pigs.

BACKGROUND: We studied a novel approach for the evaluation and management of volemia: minimally invasive monitoring of respiratory blood flow variations in the superior vena cava (SVC). We performed an experiment with 10 crossbred (Landrace × large white) female pigs (Sus scrofa domestica). METHODS: Hypovolemia was induced by bleeding from a femoral artery, in six stages. This was followed by blood return and then an infusion of 1000 ml saline, resulting in hypervolemia. Flow in the SVC was measured by Flowire (Volcano corp., USA), located in a distal channel of a triple-lumen central venous catheter. The key parameters measured were venous return variation index (VRV)-a new index for fluid responsiveness, calculated from the maximal and minimal velocity time intervals during controlled ventilation-and systolic peak velocity (defined as peak velocity of a systolic wave using the final end-expiratory beat). A Swan-Ganz catheter (Edwards Lifesciences, USA) was introduced into the pulmonary artery to measure pulmonary arterial pressure, pulmonary capillary wedge pressure, and continuous cardiac output measurements, using the Vigilance monitor (Edwards Lifesciences, USA). RESULTS: We analyzed 44 VRV index measurements during defined hemodynamic status events. The curves of VRV indexes for volume responders and volume non-responders intersected at a VRV value of 27, with 10% false negativity and 2% false positivity. We compared the accuracy of VRV and pulse pressure variations (PPV) for separation of fluid responders and fluid non-responders using receiver operating characteristic (ROC) curves. VRV was better (AUCROC 0.96) than PPV (AUCROC 0.85) for identification of fluid responders. The VRV index exhibited the highest relative change during both hypovolemia and hypervolemia, compared to standard hemodynamic measurement. CONCLUSIONS: The VRV index provides a real-time method for continuous assessment of fluid responsiveness. It combines the advantages of echocardiography-based methods with a direct and continuous assessment of right ventricular filling during mechanical ventilation.

Non-invasive endothelial function assessment using digital reactive hyperaemia correlates with three-dimensional intravascular ultrasound and virtual histology-derived plaque volume and plaque phenotype.

BACKGROUND AND AIM: To study relationships between endothelial dysfunction (ED) and coronary atherosclerosis derived from intravascular ultrasound (IVUS) and virtual histology (VH). METHODS: Endothelial dysfunction was examined by EndoPAT system (Itamar Medical) in 56 patients who underwent IVUS and VH (Volcano corp.). Reactive hyperaemia index (RHI) < 2 was used for definition of ED. IVUS sequences were divided into 5 mm-long non-overlapping and adjacent vessel segments. Plaque phenotype was determined for each frame and 5 mm vessel segment was labeled according to highest frame score (from 0 for "no lesion" to 5 for "thin cap fibroatheroma; TCFA"). RESULTS: IVUS-VH data were collected from 41 patients suitable for three-dimensional analysis. Patients with ED exhibited larger plaque burden than those without ED (0.46 ± 0.08 vs. 0.39 ± 0.07, p = 0.014), smaller lumen area (8.59 ± 2.19 vs. 11.90 ± 3.50, p = 0.016), higher plaque risk score (2.82 ± 1.18 vs. 1.84 ± 0.90, p = 0.012), and higher number of TCFA frames (0.36 ± 0.22 vs. 0.22 ± 0.16, p = 0.038). Relative amounts of fibrous tissue correlated positively with RHI (p = 0.034, r = 0.33). The numbers of fibroatheromas and calcified plaques correlated with RHI inversely (r = -0.34, p = 0.031 and r = -0.32, p = 0.044, respectively). CONCLUSIONS: Endothelial dysfunction correlates with severity and phenotype of coronary lesions and can contribute to non-invasive detection of individuals with higher risk of cardiovascular events.

Hyperinvasive approach to out-of hospital cardiac arrest using mechanical chest compression device, prehospital intraarrest cooling, extracorporeal life support and early invasive assessment compared to standard of care. A randomized parallel groups comparative study proposal. "Prague OHCA study".

BACKGROUND: Out of hospital cardiac arrest (OHCA) has a poor outcome. Recent non-randomized studies of ECLS (extracorporeal life support) in OHCA suggested further prospective multicenter studies to define population that would benefit from ECLS. We aim to perform a prospective randomized study comparing prehospital intraarrest hypothermia combined with mechanical chest compression device, intrahospital ECLS and early invasive investigation and treatment in all patients with OHCA of presumed cardiac origin compared to a standard of care. METHODS: This paper describes methodology and design of the proposed trial. Patients with witnessed OHCA without ROSC (return of spontaneous circulation) after a minimum of 5 minutes of ACLS (advanced cardiac life support) by emergency medical service (EMS) team and after performance of all initial procedures (defibrillation, airway management, intravenous access establishment) will be randomized to standard vs. hyperinvasive arm. In hyperinvasive arm, mechanical compression device together with intranasal evaporative cooling will be instituted and patients will be transferred directly to cardiac center under ongoing CPR (cardiopulmonary resuscitation). After admission, ECLS inclusion/exclusion criteria will be evaluated and if achieved, veno-arterial ECLS will be started. Invasive investigation and standard post resuscitation care will follow. Patients in standard arm will be managed on scene. When ROSC achieved, they will be transferred to cardiac center and further treated as per recent guidelines. PRIMARY OUTCOME: 6 months survival with good neurological outcome (Cerebral Performance Category 1-2). Secondary outcomes will include 30 day neurological and cardiac recovery. DISCUSSION: Authors introduce and offer a protocol of a proposed randomized study comparing a combined "hyperinvasive approach" to a standard of care in refractory OHCA. The protocol is opened for sharing by other cardiac centers with available ECLS and cathlab teams trained to admit patients with refractory cardiac arrest under ongoing CPR. A prove of concept study will be started soon. The aim of the authors is to establish a net of centers for a multicenter trial initiation in future. ETHICS AND REGISTRATION: The protocol has been approved by an Institutional Review Board, will be supported by a research grant from Internal Grant Agency of the Ministry of Health, Czech Republic NT 13225-4/2012 and has been registered under ClinicalTrials.gov identifier: NCT01511666.

Left atrial flow propagation velocity: a new approach for assessment of left atrial reservoir function.

To assess the feasibility of left atrial flow propagation velocity (LAFPV) measurement and to evaluate the influence of preload alterations on this new parameter of left atrial (LA) reservoir function as compared to conventional echocardiographic indices. 30 healthy volunteers (26 ± 5 years, 20 males) underwent echocardiographic examination at rest, during passive leg lifting and after sublingual administration of nitroglycerine with subsequent Valsalva maneuver. LA reservoir function was assessed by conventional indices including LA expansion index, peak velocity and velocity-time integral of pulmonary venous systolic flow. As well, LAFPV was measured by color M-mode in an apical 4-chamber view as the slope of the transatrial flow wave during LA reservoir phase. LAFPV measurement was feasible in 25 subjects (83%). All conventional parameters of LA reservoir function were significantly altered from resting values by both load-modifying conditions. However, LAPFV was not significantly altered by such maneuvers (228 ± 28 cm s⁻¹ at rest vs. 238 ± 3 cm s⁻¹ during leg lifting, P = NS, vs. 218 ± 38 cm s(-1) after nitroglycerin with Valsalva maneuver, P = NS vs. rest, P < 0.01 vs. leg lifting). LAFPV can be measured in a majority of subjects and represents a new, less load-dependent index of LA reservoir function that may more appropriately reflect LA compliance.