Duval, Sue

Background: Pre-clinical animal studies have demonstrated improved cerebral blood flow and neurological survival with Automated Head Up Position (AHUP) cardiopulmonary resuscitation (CPR) as compared to flat conventional (C) CPR. AHUP CPR consists of 1) automated head and thorax elevation 2) active compression decompression CPR and 3) an impedance threshold device. Subsequently, observational propensity-matched studies of out-of-hospital cardiac arrest (OHCA) patients demonstrated a time-dependent association between survival with intact neurological function (SNF) and application of AHUP CPR. However, comparison of AHUP CPR outcomes with contemporaneous C-CPR controls is lacking. Hypothesis: Use of AHUP CPR for OHCA by first responder agencies will demonstrate a higher incidence of SNF compared to C-CPR outcomes from a national registry Methods: Data from the previous 5 years (2020-2024) from an AHUP-CPR Registry comprised of OHCA patients routinely treated by first responders with AHUP CPR were compared with data from the Cardiac Arrest Registry to Enhance Survival (CARES). Patient demographics, arrest characteristics, ROSC, SHD, and SNF were recorded. SNF was defined as a Cerebral Performance Category 1 or 2 at hospital discharge. A two-sample test of proportions was used for outcome comparisons. Results: Nine AHUP registry sites (MN, FL, TN, IL, OK, VA, AL, IA, MI) were included. Summary 5-year demographics (Table 1) and clinical outcomes (Table 2) are presented. For 2020-2024 AHUP sites, the average time (mm:ss, SD) from 9-1-1 call to start of CPR was 9:09 (4:37) and time to start of AHUP CPR was 12:46 (5:57). The AHUP registry had a higher 5-yr incidence of SNF versus the CARES registry (difference 2.8%, 95% CI 1.8-3.8, p < 0.00001). This difference was consistent year over year (Figure 1). Secondary outcomes of sustained return of spontaneous circulation and survival to hospital discharge in the AHUP registry were also significantly higher than CARES registry data (Table 2). Conclusions: Over a 5-year period, an unadjusted analysis of aggregate data from two OHCA patient registries demonstrated that the incidence of survival with intact neurological function was higher in patients treated with AHUP CPR as part of first responder care versus patients treated with more conventional CPR methods.

Background: Active compression-decompression (ACD) cardiopulmonary resuscitation (CPR), an impedance threshold device (ITD) and controlled, gradual, automated head and thorax elevation, collectively termed automated Head Up Position (AHUP) CPR, increases cerebral perfusion pressure (CerPP), brain blood flow, coronary perfusion pressure (CorPP), end tidal CO2 (ETCO2) and cerebral oximetry (rSO2) in animal models when compared with conventional (C) CPR. AHUP-CPR in patients is associated with increased neurologically favorable survival versus C-CPR. This study tested the hypothesis that AHUP CPR will increase cardiac stroke volume (SV) and other hemodynamics compared with C-CPR in a porcine model of cardiac arrest. Methods: Farm pigs (n=15) were sedated, anesthetized, and ventilated. Hemodynamics, including intracardiac conductance catheter based biventricular (BiV) pressure-volume (PV) loops, were continuously measured and recorded. After 10 minutes of untreated ventricular fibrillation, C-CPR was performed for 2 minutes in the supine position using an automated CPR device designed for pigs at a rate of 100 compressions/minute, depth of 21% of the chest antero-postero diameter, a 50% duty cycle, and no active decompression. ACD+ITD was then performed with 3 cm of active decompression for 2 minutes, followed by AHUP-CPR, where the head and thorax were initially raised to 10 cm and 8 cm for a 2-minute priming phase, followed by elevation over the next 2 minutes to 24 cm and 9 cm. A linear mixed-effects model with a random intercept for individual pigs was used for statistical analysis. Results: CerPP, CorPP, ETCO2, and rSO2, as well as BiV SV and cardiac output, increased progressively and significantly with implementation of AHUP-CPR (p<0.05). C-CPR generated a right ventricular (RV) SV of 25.0 mL (48% of baseline pre-VF) and left ventricular (LV) SV of 17.5 mL (39% of baseline). ACD+ITD significantly increased RV and LV SV by an average of ~ 48% versus C-CPR; AHUP-CPR further increased BiV SV by an average of ~ 83%, reaching 85% and 75% of RV and LV pre-VF values, respectively. (Figure 1) Conclusion: This study demonstrated biventricular stroke volume is significantly augmented with AHUP-CPR versus C-CPR or ACD+ITD in the flat position. These findings, together with AHUP-enhanced higher ETCO2, rSO2, and CerPP values versus C-CPR or ACD-CPR in the flat position, help explain the improved clinical outcomes associated with early use of AHUP-CPR.

Background: Active compression-decompression cardiopulmonary resuscitation (ACD-CPR) combined with an impedance threshold device (ITD) and controlled head-up positioning, collectively termed AHUP-CPR, is associated with improved outcomes compared with conventional CPR (C-CPR). Active decompression (AD) forcibly lifts the anterior chest wall with suction after each compression, while the ITD simultaneously impedes airflow into the lungs. AD and ITD synergistically lower intrathoracic pressure during decompression, improving venous return, ventricular refilling and cardiac output. Concurrently, head-up positioning lowers intracranial pressures and improves cardiac preload. This pig study focused on the physiological role of AD during AHUP-CPR, simulating real clinical scenarios. Methods: Ten male and female farm pigs (~40 kg) were anesthetized, intubated and ventilated. Hemodynamic parameters, end-tidal CO2 (ETCO2), and biventricular pressure-volume loops were recorded continuously. Ventricular fibrillation was induced and left untreated for 10 mins. Then, after 2 min of automated C-CPR in the flat position, AHUP-CPR with a 3 cm lift above the neutral position of the chest was performed for 13 min. AD was then abruptly discontinued, restarted 1 min later, and increased incrementally every min to up to 4 cm of active lift. Data were analyzed with a linear mixed-effects model, using random intercepts for individual pigs. Results: Upon cessation of AD, coronary and cerebral perfusion pressures, compression and decompression aortic pressures, compression right atrial pressure, ETCO2, right and left ventricular preload, compliance, stroke volume and cardiac output all decreased immediately and significantly (p<0.01), whereas decompression right atrial and biventricular pressures increased. With restoration of AD, physiological parameters returned to ≥ 90% of pre-AD discontinuation values (Figures 1 and 2). Conclusion: Full chest wall lift, achieved with > 3 cm of AD, was needed to maintain and optimize hemodynamics during AHUP-CPR in pigs. After pausing AD, incremental restoration of AD resulted in nearly complete restoration of peripheral and central hemodynamic measures. These observations support the benefit of and need for ≥3 cm of AD to optimize AHUP-CPR. Effective means to generate ≥3 cm of AD should be considered when implementing and developing AHUP-CPR devices to optimize outcomes.

Background Recent guidelines have emphasized the use of medical management, early diagnosis, and a multidisciplinary team to effectively treat patients with critical limb ischemia (CLI). Previous literature briefly highlighted the current racial disparities in its intervention. Herein, we analyze the trend over a 14‐year time period to investigate whether the disparities gap in CLI management is closing. Methods and Results The National Inpatient Sample was queried between 2005 and 2018 for hospitalizations involving CLI. Nontraumatic amputations and revascularization were identified. Utilization trends of these procedures were compared between races (White, Black, Hispanic, Asian and Pacific Islander, Native American, and Other). Multivariable regression assessed differences in race regarding procedure usage. There were 6 904 562 admissions involving CLI in the 14‐year study period. The rate of admissions in White patients who received any revascularization decreased by 0.23% ( P <0.001) and decreased by 0.25% ( P =0.025) for Asian and Pacific Islander patients. Among all patients, the annual rate of admission in White patients who received any amputation increased by 0.21% ( P <0.001), increased by 0.19% ( P =0.001) for Hispanic patients, and increased by 0.19% ( P =0.012) for the Other race patients. Admissions involving Black, Hispanic, Asian and Pacific Islander, or Other race patients had higher odds of receiving any revascularization compared with White patients. All races had higher odds of receiving major amputation compared with White patients. Conclusions Our analysis highlights disparities in CLI treatment in our nationally representative sample. Non‐White patients are more likely to receive invasive treatments, including major amputations and revascularization for CLI, compared with White patients.

Background Current mortality data for pulmonary arterial hypertension (PAH) in the United States are based on registries that enrolled patients prior to 2010. We sought to determine mortality in PAH in the modern era using the PHAR (Pulmonary Hypertension Association Registry). Methods and Results We identified all adult patients with PAH enrolled in the PHAR between September 2015 and September 2020 (N=935). We used Kaplan‐Meier survival analysis and Cox proportional hazards models to assess mortality at 1, 2, and 3 years. Patients were stratified based on disease severity by 3 validated risk scores. In treatment‐naïve patients, we compared survival based on initial treatment strategy. The median age was 56 years (44–68 years), and 76% were women. Of the 935 patients, 483 (52%) were ≤6 months from PAH diagnosis. There were 121 deaths (12.9%) during a median follow‐up time of 489 days (281–812 days). The 1‐, 2‐, and 3‐year mortality was 8% (95% CI, 6%–10%), 16% (95% CI, 13%–19%), and 21% (95% CI, 17%–25%), respectively. When stratified into low‐, intermediate‐, and high‐risk PAH, the mortality at 1, 2, and 3 years was 1%, 4% to 6%, and 7% to 11% for low risk; 7% to 8%, 11% to 16%, and 18% to 20% for intermediate risk; and 12% to 19%, 22% to 38%, and 28% to 55% for high risk, respectively. In treatment‐naïve patients, initial combination therapy was associated with better 1‐year survival (adjusted hazard ratio, 0.43 [95% CI, 0.19–0.95]; P =0.037). Conclusions Mortality in the intermediate‐ and high‐risk patients with PAH remains unacceptably high in the PHAR, suggesting the importance for early diagnosis, aggressive use of available therapies, and the need for better therapeutics.

Background: Atrial fibrillation (AF) is associated with increased risk of hospitalization. However, little is known about the impact of AF on non-inpatient healthcare utilization or about sex or race differences in AF-related utilization. We examined rates of inpatient and outpatient utilization by AF status in the Atherosclerosis Risk in Communities (ARIC) study. Methods and Results: ARIC cohort participants with incident AF enrolled in fee-for-service Medicare, Parts A and B, for at least 12 continuous months between 1991 and 2009 were matched on age, sex, race and center to up to three participants without AF. Healthcare utilization was ascertained from inpatient and outpatient Medicare claims and classified based on primary ICD-9 code. The analysis included 944 AF and 2,761 non-AF participants. The average number of days hospitalized per year was 13.1 (95% confidence interval [CI]: 11.5-15.0) and 2.8 (95% CI: 2.5-3.1) for those with and without AF, respectively. The corresponding number of outpatient claims per year was 53.2 (95% CI: 50.4-56.1) and 23.0 (95% CI: 22.2-23.8) for those with and without AF, respectively (Table). Most utilization in AF patients was attributable to non-AF conditions, particularly other-cardiovascular disease (CVD)-related reasons; the adjusted rate ratio for days hospitalized per year for other-CVD-related reasons was 4.76 (95% CI: 3.51 - 6.44) for those with compared to those without AF. There was suggestive evidence that sex modified the association between AF and inpatient utilization, with AF related to greater utilization in women than men. The association between AF and healthcare utilization was similar in whites and blacks. Conclusions: This study highlights the considerably greater healthcare utilization (inpatient and outpatient) among those with AF; the differential in utilization due to other-CVD-related reasons was substantial. In addition to recommended heart rate or rhythm treatment, accompanying cardiovascular comorbidities should be evaluated and managed.

Statistical analyses are a crucial component of the biomedical research process and are necessary to draw inferences from biomedical research data. The application of sound statistical methodology is a prerequisite for publication in the American Heart Association (AHA) journal portfolio. The objective of this document is to summarize key aspects of statistical reporting that might be most relevant to the authors, reviewers, and readership of AHA journals. The AHA Scientific Publication Committee convened a task force to inventory existing statistical standards for publication in biomedical journals and to identify approaches suitable for the AHA journal portfolio. The experts on the task force were selected by the AHA Scientific Publication Committee, who identified 12 key topics that serve as the section headers for this document. For each topic, the members of the writing group identified relevant references and evaluated them as a resource to make the standards summarized herein. Each section was independently reviewed by an expert reviewer who was not part of the task force. Expert reviewers were also permitted to comment on other sections if they chose. Differences of opinion were adjudicated by consensus. The standards presented in this report are intended to serve as a guide for high-quality reporting of statistical analyses methods and results.

Background: Paclitaxel-containing devices (PTXDs) significantly reduce reintervention in patients with symptomatic femoropopliteal peripheral artery disease. A recent aggregate-data meta-analysis reported increased late mortality in patients with peripheral artery disease treated with PTXDs. We performed an individual patient data meta-analysis to evaluate mortality. Methods: Manufacturers of US Food and Drug Administration–approved and commercially available devices in the United States provided deidentified individual patient data for independent analysis. Cox proportional hazards 1-stage meta-analysis models using intention-to-treat methods were used for the primary analysis. A secondary analysis of recovered missing vital status data was performed. The impact of control crossover to PTXDs, cause-specific mortality, and drug dose mortality were assessed. Results: A total of 2185 subjects and 386 deaths from 8 PTXD trials with 4-year median follow-up were identified. The primary analysis indicated a 38% (95% CI, 6% to 80%) increased relative mortality risk, corresponding to 4.6% absolute increase, at 5 years associated with PTXD use. Control and treatment arm loss to follow-up and withdrawal were 24% and 23%, respectively. With inclusion of recovered vital status data, the excess relative mortality risk was 27% (95% CI, 3%–58%). This observation was consistent across various scenarios, including as-treated analyses, with no evidence of increased risk over time with PTXDs. Mortality risk tended to be increased for all major causes of death. There were no subgroup differences. No drug dose–mortality association was identified. Conclusions: This individual patient data meta-analysis, based on the most complete available data set of mortality events from PTXD randomized controlled trials, identified an absolute 4.6% increased mortality risk associated with PTXD use.

Background No previous study has evaluated the impact of past US Preventive Services Task Force statements on primary prevention ( PP ) aspirin use in a primary care setting. The aim of this study was to evaluate temporal changes in PP aspirin use in a primary care population, stratifying patients by their 10‐year global cardiovascular disease risk, in response to the 2009 statement. Methods and Results This study estimated biannual aspirin use prevalence using electronic health record data from primary care clinics within the Fairview Health System (Minnesota) from 2007 to 2015. A total of 94 270 patient encounters had complete data to estimate a 10‐year cardiovascular disease risk score using the 2013 American College of Cardiology/American Heart Association global risk estimator. Patients were stratified into low‐ (<10%), intermediate‐ (10–20%), and high‐ (≥20%) risk groups. Over the 9‐year period, PP aspirin use averaged 43%. When stratified by low, intermediate and high risk, average PP aspirin use was 41%, 63%, and 73%, respectively. Average PP aspirin use decreased after the publication of the 2009 US Preventive Services Task Force recommendation statement: from 45% to 40% in the low‐risk group; from 66% to 62% in the intermediate‐risk group; and from 76% to 73% in the high‐risk group, before and after the guideline. Conclusions Publication of the 2009 US Preventive Services Task Force recommendation was not associated with an increase in aspirin use. High risk PP patients utilized aspirin at high rates. Patients at intermediate risk were less intensively treated, and patients at low risk used aspirin at relatively high rates. These data may inform future aspirin guideline dissemination.