Rationale and design of the PRAETORIAN-COVID trial:A double-blind, placebo-controlled randomized clinical trial with valsartan for PRevention of Acute rEspiraTORy dIstress syndrome in hospitAlized patieNts with SARS-COV-2 Infection Disease

There is much debate on the use of angiotensin receptor blockers (ARBs) in severe acute respiratory syndrome–coronavirus-2 (SARS-CoV-2)–infected patients. Although it has been suggested that ARBs might lead to a higher susceptibility and severity of SARS-CoV-2 infection, experimental data suggest that ARBs may reduce acute lung injury via blocking angiotensin-II–mediated pulmonary permeability, inflammation, and fibrosis. However, despite these hypotheses, specific studies on ARBs in SARS-CoV-2 patients are lacking. Methods: The PRAETORIAN-COVID trial is a multicenter, double-blind, placebo-controlled 1:1 randomized clinical trial in adult hospitalized SARS-CoV-2–infected patients (n = 651). The primary aim is to investigate the effect of the ARB valsartan compared to placebo on the composite end point of admission to an intensive care unit, mechanical ventilation, or death within 14 days of randomization. The active-treatment arm will receive valsartan in a dosage titrated to blood pressure up to a maximum of 160 mg bid, and the placebo arm will receive matching placebo. Treatment duration will be 14 days, or until the occurrence of the primary end point or until hospital discharge, if either of these occurs within 14 days. The trial is registered at clinicaltrials.gov (NCT04335786, 2020). The PRAETORIAN-COVID trial is a double-blind, placebo-controlled 1:1 randomized trial to assess the effect of valsartan compared to placebo on the occurrence of ICU admission, mechanical ventilation, and death in hospitalized SARS-CoV-2–infected patients. The results of this study might impact the treatment of SARS-CoV-2 patients globally

A novel intra-ventricular assist device enhances cardiac performance in normal and acutely failing isolated porcine hearts

Background: We recently demonstrated that a novel intra-ventricular membrane pump (IVMP) was able to increase the pump function of isolated beating porcine hearts. In follow-up, we now investigated the impact of the IVMP on myocardial oxygen consumption and total mechanical efficiency (TME) and assessed the effect of IVMP-support in acutely failing hearts. Methods: In 10 ex vivo beating porcine hearts, we studied hemodynamic parameters, as well as arterial and coronary venous oxygen content. We assessed cardiac power (CP), myocardial oxygen consumption (MVO 2), and TME (CP divided by MVO 2) under baseline conditions and during IVMP-support. Additionally, five isolated hearts were subjected to global hypoxia to investigate the effects of IVMP-support on CP under conditions of acute heart failure. Results: Under physiological conditions, baseline CP was 0.36 ± 0.10 W, which increased to 0.65 ± 0.16 W during IVMP-support (increase of 85% ± 24, p < 0.001). This was accompanied by an increase in MVO2 from 18.6 ± 6.2 ml/min at baseline, to 22.3 ± 5.0 ml/min during IVMP-support (+26 ± 31%, p = 0.005). As a result, TME (%) increased from 5.9 ± 1.2 to 8.8 ± 1.8 (50 ± 22% increase, p < 0.001). Acute hypoxia-induced cardiac pump failure reduced CP by 35 ± 6%, which was fully restored to baseline levels during IVMP-support in all hearts. Conclusion: IVMP-support improved mechanical efficiency under physiological conditions, as the marked increase in cardiac performance only resulted in a modest increase in oxygen consumption. Moreover, the IVMP rapidly restored cardiac performance under conditions of acute pump failure. These observations warrant further study, to evaluate the effects of IVMP-support in in vivo animal models of acute cardiac pump failure

Pilot study on VF-waveform based algorithms for early detection of acute myocardial infarction during out-of-hospital cardiac arrest

Introduction: On-scene detection of acute coronary occlusion (ACO) during ongoing ventricular fibrillation (VF) may facilitate patient-tailored triage and treatment during cardiac arrest. Experimental studies have demonstrated the diagnostic potential of the amplitude spectrum area (AMSA) of the VF-waveform to detect myocardial infarction (MI). In follow-up, we performed this clinical pilot study on VF-waveform based discriminative models to diagnose acute MI due to ACO in real-world VF-patients. Methods: In our registry of VF-patients transported to a tertiary hospital (Nijmegen, The Netherlands), we studied patients with high-quality VF-registrations. We calculated VF-characteristics prior to the first shock, and first-to-second shock changes (Δ-characteristics). Primary aim was to assess the discriminative ability of the AMSA to detect patients with ACO. Secondarily, we investigated the discriminative value of adding ΔAMSA-measures using machine learning algorithms. Model performances were assessed using C-statistics. Results: In total, there were 67 VF-patients with and 34 without an ACO, and baseline characteristics did not differ significantly. Based on the AMSA prior to the first defibrillation attempt, discrimination between ACO and non-ACO was possible, with a C-statistic of 0.66 (0.56–0.75). The discriminative model using AMSA + ΔAMSA yielded a C-statistic of 0.80 (0.69–0.88). Conclusion: These clinical pilot data confirm previous experimental findings that early detection of MI using VF-waveform analysis seems feasible, and add insights on the diagnostic impact of accounting for first-to-second shock changes in VF-characteristics. Confirmative studies in larger cohorts and with a variety of VF-algorithms are warranted to further investigate the potential of this innovative approach

Long-term Effect of Face-to-Face vs Virtual Reality Cardiopulmonary Resuscitation (CPR) Training on Willingness to Perform CPR, Retention of Knowledge, and Dissemination of CPR Awareness: A Secondary Analysis of a Randomized Clinical Trial

Importance: Increased bystander cardiopulmonary resuscitation (CPR) is essential to improve survival after cardiac arrest. Although most studies focus on technical CPR skills, the randomized Lowlands Saves Lives trial prespecified a follow-up survey on other important aspects that affect the widespread performance of CPR. Objective: To investigate bystander willingness to perform CPR on a stranger, theoretical knowledge retention, and dissemination of CPR awareness 6 months after undergoing short face-to-face and virtual reality (VR) CPR trainings. Design, Setting, and Participants: A prespecified 6-month posttraining survey was conducted among 320 participants in the Lowlands Saves Lives trial, a randomized comparison between 20-minute face-to-face, instructor-led CPR training and VR training. Participants were recruited at the Lowlands music festival, with a designated area to conduct scientific projects (August 16-18, 2019; the Netherlands). Statistical analysis was performed from March 1, 2020, to July 31, 2021. Interventions: Two standardized 20-minute protocols on CPR and automated external defibrillator use: instructor-led face-to-face training using CPR manikins or VR training using the Resuscitation Council (UK)-endorsed Lifesaver VR smartphone application and a pillow to practice compressions. Main Outcomes and Measures: Primary outcomes were willingness to perform CPR on a stranger, theoretical knowledge retention, and dissemination of CPR awareness as reported by the entire cohort. As secondary analyses, the results of the 2 training modalities were compared. Results: Of 381 participants, 320 consented to this follow-up survey; 188 participants (115 women [61%]; median age, 26 years [IQR, 22-32 years]) completed the entire survey and were accordingly included in the secondary analysis. The overall proportion of participants willing to perform CPR on a stranger was 77% (144 of 188): 81% (79 of 97) among face-to-face participants and 71% (65 of 91) among VR participants (P =.02); 103 participants (55%) reported feeling scared to perform CPR (P =.91). Regarding theoretical knowledge retention, a median of 7 (IQR, 6-8) of 9 questions were answered correctly in both groups (P =.81). Regarding dissemination of CPR awareness, 65% of participants (123 of 188) told at least 1 to 10 family members or friends about the importance of CPR, and 15% (29 of 188) had participated in certified, instructor-led training at the time of the survey, without differences between groups. Conclusions and Relevance: In this 6-month posttraining survey, young adult participants of short CPR training modules reported high willingness (77%) to perform CPR on a stranger, with slightly higher rates for face-to-face than for VR participants. Theoretical knowledge retention was good, and the high dissemination of awareness suggests that these novel CPR training modules staged at a public event are promising sensitizers for involvement in CPR, although further challenges include mitigating the fear of performing CPR. Trial Registration: ClinicalTrials.gov Identifier: NCT04013633

Ventricular fibrillation waveform characteristics differ according to the presence of a previous myocardial infarction: A surface ECG study in ICD-patients

Background:\ud Characteristics of the ventricular fibrillation (VF) waveform reflect arrest duration and have been incorporated in studies on algorithms to guide resuscitative interventions. Findings in animals indicate that VF characteristics are also affected by the presence of a previous myocardial infarction (MI). As studies in humans are scarce, we assessed the impact of a previous MI on VF characteristics in ICD-patients.\ud \ud Methods:\ud Prospective cohort of ICD-patients (n = 190) with defibrillation testing at the Radboudumc (2010–2013). VF characteristics of the 12-lead surface ECG were compared between three groups: patients without a history of MI (n = 88), with a previous anterior (n = 47) and a previous inferior MI (n = 55).\ud \ud Results:\ud As compared to each of the other groups, the mean amplitude and amplitude spectrum area were lower, for an anterior MI in lead V3 and for an inferior MI in leads II and aVF. Across the three groups, the bandwidth was broader in the leads corresponding with the infarct localisation. In contrast, the dominant and median frequencies only differed between previous anterior MI and no history of MI, being lower in the former.\ud \ud Conclusions:\ud The VF waveform is affected by the presence of a previous MI. Amplitude-related measures were lower and VF was less organised in the ECG-lead(s) adjacent to the area of infarction. Although VF characteristics of the surface ECG have so far primarily been considered a proxy for arrest duration and metabolic state, our findings question this paradigm and may provide additional insights into the future potential of VF-guided resuscitative interventions

Central and local arterial stiffness in White Europeans compared to age-, sex-, and BMI-matched South Asians

BackgroundEthnicity impacts cardiovascular disease (CVD) risk, and South Asians demonstrate a higher risk than White Europeans. Arterial stiffness is known to contribute to CVD, and differences in arterial stiffness between ethnicities could explain the disparity in CVD risk. We compared central and local arterial stiffness between White Europeans and South Asians and investigated which factors are associated with arterial stiffness.MethodsData were collected from cohorts of White Europeans (the Netherlands) and South Asians (India). We matched cohorts on individual level using age, sex, and body mass index (BMI). Arterial stiffness was measured with ARTSENS® Plus. Central stiffness was expressed as carotid-femoral pulse wave velocity (cf-PWV, m/s), and local carotid stiffness was quantified using the carotid stiffness index (Beta) and pressure-strain elastic modulus (Epsilon, kPa). We compared arterial stiffness between cohorts and used multivariable linear regression to identify factors related to stiffness.ResultsWe included n = 121 participants per cohort (age 53±10 years, 55% male, BMI 24 kg/m2). Cf-PWV was lower in White Europeans compared to South Asians (6.8±1.9 vs. 8.2±1.8 m/s, p0.05 for interaction). Systolic blood pressure was associated with carotid stiffness in both cohorts, whereas age was associated to carotid stiffness only in South Asians and BMI only in White Europeans.ConclusionEthnicity is associated with central but not local arterial stiffness. Conversely, ethnicity seems to modify associations between CVD risk factors and local but not central arterial stiffness. This suggests that ethnicity interacts with arterial stiffness measures and the association of these measures with CVD risk factors

Central and local arterial stiffness in White Europeans compared to age-, sex-, and BMI-matched South Asians

Background Ethnicity impacts cardiovascular disease (CVD) risk, and South Asians demonstrate a higher risk than White Europeans. Arterial stiffness is known to contribute to CVD, and differences in arterial stiffness between ethnicities could explain the disparity in CVD risk. We compared central and local arterial stiffness between White Europeans and South Asians and investigated which factors are associated with arterial stiffness. Methods Data were collected from cohorts of White Europeans (the Netherlands) and South Asians (India). We matched cohorts on individual level using age, sex, and body mass index (BMI). Arterial stiffness was measured with ARTSENS® Plus. Central stiffness was expressed as carotid-femoral pulse wave velocity (cf-PWV, m/s), and local carotid stiffness was quantified using the carotid stiffness index (Beta) and pressure-strain elastic modulus (Epsilon, kPa). We compared arterial stiffness between cohorts and used multivariable linear regression to identify factors related to stiffness. Results We included n = 121 participants per cohort (age 53±10 years, 55% male, BMI 24 kg/m2). Cf-PWV was lower in White Europeans compared to South Asians (6.8±1.9 vs. 8.2±1.8 m/s, p0.05 for interaction). Systolic blood pressure was associated with carotid stiffness in both cohorts, whereas age was associated to carotid stiffness only in South Asians and BMI only in White Europeans. Conclusion Ethnicity is associated with central but not local arterial stiffness. Conversely, ethnicity seems to modify associations between CVD risk factors and local but not central arterial stiffness. This suggests that ethnicity interacts with arterial stiffness measures and the association of these measures with CVD risk factors