F1ALA: ultrafast and memory-efficient ancestral lineage annotation applied to the huge SARS-CoV-2 phylogeny.

The unprecedentedly large size of the global SARS-CoV-2 phylogeny makes any computation on the tree difficult. Lineage identification (e.g. the PANGO nomenclature for SARS-CoV-2) and assignment are key to track the virus evolution. It requires annotating clade roots of lineages to unlabeled ancestral nodes in a phylogenetic tree. Then the lineage labels of descendant samples under these clade roots can be inferred to be the corresponding lineages. This is the ancestral lineage annotation problem, and matUtils (a package in pUShER) and PastML are commonly used methods. However, their computational tractability is a challenge and their accuracy needs further exploration in huge SARS-CoV-2 phylogenies. We have developed an efficient and accurate method, called "F1ALA", that utilizes the F1-score to evaluate the confidence with which a specific ancestral node can be annotated as the clade root of a lineage, given the lineage labels of a set of taxa in a rooted tree. Compared to these methods, F1ALA achieved roughly an order of magnitude faster yet with ∼12% of their memory usage when annotating 2277 PANGO lineages in a phylogeny of 5.26 million taxa. F1ALA allows real-time lineage tracking to be performed on a laptop computer. F1ALA outperformed matUtils (pUShER) with statistical significance, and had comparable accuracy to PastML in tests on empirical and simulated data. F1ALA enables a tree refinement by pruning taxa with inconsistent labels to their closest annotation nodes and re-inserting them back to the pruned tree to improve a SARS-CoV-2 phylogeny with both higher log-likelihood and lower parsimony score. Given the ultrafast speed and high accuracy, we anticipated that F1ALA will also be useful for large phylogenies of other viruses. Codes and benchmark datasets are publicly available at https://github.com/id-bioinfo/F1ALA.

Insurance-based Disparities in Outcomes and Extracorporeal Membrane Oxygenation Utilization for Hospitalized COVID-19 Patients.

BACKGROUND: The objective of this study was to examine insurance-based disparities in mortality, nonhome discharges, and extracorporeal membrane oxygenation utilization in patients hospitalized with COVID-19. METHODS: Using a national database of U.S. academic medical centers and their affiliated hospitals, the risk-adjusted association between mortality, nonhome discharge, and extracorporeal membrane oxygenation utilization and (1) the type of insurance coverage (private insurance, Medicare, dual enrollment in Medicare and Medicaid, and no insurance) and (2) the weekly hospital COVID-19 burden (0 to 5.0%; 5.1 to 10%, 10.1 to 20%, 20.1 to 30%, and 30.1% and greater) was evaluated. Modeling was expanded to include an interaction between payer status and the weekly hospital COVID-19 burden to examine whether the lack of private insurance was associated with increases in disparities as the COVID-19 burden increased. RESULTS: Among 760,846 patients hospitalized with COVID-19, 214,992 had private insurance, 318,624 had Medicare, 96,192 were dually enrolled in Medicare and Medicaid, 107,548 had Medicaid, and 23,560 had no insurance. Overall, 76,250 died, 211,702 had nonhome discharges, 75,703 were mechanically ventilated, and 2,642 underwent extracorporeal membrane oxygenation. The adjusted odds of death were higher in patients with Medicare (adjusted odds ratio, 1.28 [95% CI, 1.21 to 1.35]; P < 0.0005), dually enrolled (adjusted odds ratio, 1.39 [95% CI, 1.30 to 1.50]; P < 0.0005), Medicaid (adjusted odds ratio, 1.28 [95% CI, 1.20 to 1.36]; P < 0.0005), and no insurance (adjusted odds ratio, 1.43 [95% CI, 1.26 to 1.62]; P < 0.0005) compared to patients with private insurance. Patients with Medicare (adjusted odds ratio, 0.47; [95% CI, 0.39 to 0.58]; P < 0.0005), dually enrolled (adjusted odds ratio, 0.32 [95% CI, 0.24 to 0.43]; P < 0.0005), Medicaid (adjusted odds ratio, 0.70 [95% CI, 0.62 to 0.79]; P < 0.0005), and no insurance (adjusted odds ratio, 0.40 [95% CI, 0.29 to 0.56]; P < 0.001) were less likely to be placed on extracorporeal membrane oxygenation than patients with private insurance. Mortality, nonhome discharges, and extracorporeal membrane oxygenation utilization did not change significantly more in patients with private insurance compared to patients without private insurance as the COVID-19 burden increased. CONCLUSIONS: Among patients with COVID-19, insurance-based disparities in mortality, nonhome discharges, and extracorporeal membrane oxygenation utilization were substantial, but these disparities did not increase as the hospital COVID-19 burden increased.

Blood flow kinetic energy is a novel marker for right ventricular global systolic function in patients with left ventricular assist device therapy.

Objectives: Right ventricular (RV) failure remains a major concern in heart failure (HF) patients undergoing left ventricular assist device (LVAD) implantation. We aimed to measure the kinetic energy of blood in the RV outflow tract (KE-RVOT) - a new marker of RV global systolic function. We also aimed to assess the relationship of KE-RVOT to other echocardiographic parameters in all subjects and assess the relationship of KE-RVOT to hemodynamic parameters of RV performance in HF patients. Methods: Fifty-one subjects were prospectively enrolled into 4 groups (healthy controls, NYHA Class II, NYHA Class IV, LVAD patients) as follows: 11 healthy controls, 32 HF patients (8 NYHA Class II and 24 Class IV), and 8 patients with preexisting LVADs. The 24 Class IV HF patients included 21 pre-LVAD and 3 pre-transplant patients. Echocardiographic parameters of RV function (TAPSE, St', Et', IVA, MPI) and RV outflow color-Doppler images were recorded in all patients. Invasive hemodynamic parameters of RV function were collected in all Class IV HF patients. KE-RVOT was derived from color-Doppler imaging using a vector flow mapping proprietary software. Kruskal-Wallis test was performed for comparison of KE-RVOT in each group. Correlation between KE-RVOT and echocardiographic/hemodynamic parameters was assessed by linear regression analysis. Receiver operating characteristic curves for the ability of KE-RVOT to predict early phase RV failure were generated. Results: KE-RVOT (median ± IQR) was higher in healthy controls (55.10 [39.70 to 76.43] mW/m) than in the Class II HF group (22.23 [15.41 to 35.58] mW/m, p < 0.005). KE-RVOT was further reduced in the Class IV HF group (9.02 [5.33 to 11.94] mW/m, p < 0.05). KE-RVOT was lower in the LVAD group (25.03 [9.88 to 38.98] mW/m) than the healthy controls group (p < 0.005). KE-RVOT had significant correlation with all echocardiographic parameters and no correlation with invasive hemodynamic parameters. RV failure occurred in 12 patients who underwent LVAD implantation in the Class IV HF group (1 patient was not eligible due to death immediately after the LVAD implantation). KE-RVOT cut-off value for prediction of RV failure was 9.15 mW/m (sensitivity: 0.67, specificity: 0.75, AUC: 0.66). Conclusions: KE-RVOT, a novel noninvasive measure of RV function, strongly correlates with well-established echocardiographic markers of RV performance. KE-RVOT is the energy generated by RV wall contraction. Therefore, KE-RVOT may reflect global RV function. The utility of KE-RVOT in prediction of RV failure post LVAD implantation requires further study.

Racial and Ethnic Disparities in Access to Minimally Invasive Mitral Valve Surgery.

Importance: Whether people from racial and ethnic minority groups experience disparities in access to minimally invasive mitral valve surgery (MIMVS) is not known. Objective: To investigate racial and ethnic disparities in the utilization of MIMVS. Design, Setting, and Participants: This cross-sectional study used data from the Society of Thoracic Surgeons Database for patients who underwent mitral valve surgery between 2014 and 2019. Statistical analysis was performed from January 24 to August 11, 2022. Exposures: Patients were categorized as non-Hispanic White, non-Hispanic Black, and Hispanic individuals. Main Outcomes and Measures: The association between MIMVS (vs full sternotomy) and race and ethnicity were evaluated using logistic regression. Results: Among the 103 753 patients undergoing mitral valve surgery (mean [SD] age, 62 [13] years; 47 886 female individuals [46.2%]), 10 404 (10.0%) were non-Hispanic Black individuals, 89 013 (85.8%) were non-Hispanic White individuals, and 4336 (4.2%) were Hispanic individuals. Non-Hispanic Black individuals were more likely to have Medicaid insurance (odds ratio [OR], 2.21; 95% CI, 1.64-2.98; P < .001) and to receive care from a low-volume surgeon (OR, 4.45; 95% CI, 4.01-4.93; P < .001) compared with non-Hispanic White individuals. Non-Hispanic Black individuals were less likely to undergo MIMVS (OR, 0.65; 95% CI, 0.58-0.73; P < .001), whereas Hispanic individuals were not less likely to undergo MIMVS compared with non-Hispanic White individuals (OR, 1.08; 95% CI, 0.67-1.75; P = .74). Patients with commercial insurance had 2.35-fold higher odds of undergoing MIMVS (OR, 2.35; 95% CI, 2.06-2.68; P < .001) than those with Medicaid insurance. Patients operated by very-high volume surgeons (300 or more cases) had 20.7-fold higher odds (OR, 20.70; 95% CI, 12.7-33.9; P < .001) of undergoing MIMVS compared with patients treated by low-volume surgeons (less than 20 cases). After adjusting for patient risk, non-Hispanic Black individuals were still less likely to undergo MIMVS (adjusted OR [aOR], 0.88; 95% CI, 0.78-0.99; P = .04) and were more likely to die or experience a major complication (aOR, 1.25; 95% CI, 1.16-1.35; P < .001) compared with non-Hispanic White individuals. Conclusions and Relevance: In this cross-sectional study, non-Hispanic Black patients were less likely to undergo MIMVS and more likely to die or experience a major complication than non-Hispanic White patients. These findings suggest that efforts to reduce inequity in cardiovascular medicine may need to include increasing access to private insurance and high-volume surgeons.

Left atrial appendage exclusion with less invasive left ventricular assist device implantation.

OBJECTIVES: The objective of this single-center, pilot, prospective, and historical control study is to evaluate safety and feasibility outcomes associated with left atrial appendage exclusion (LAAE) concomitant with left ventricular assist device (LVAD) implantation via less invasive surgery (LIS) as a stroke prevention strategy. METHODS: A predefined number of 30 eligible subjects scheduled for LIS LVAD with LAAE were enrolled in the prospective arm between January 2020 and February 2021. Eligible retrospective LIS LVAD patients without LAAE were propensity-matched in a 1:1 ratio with the prospective arm subjects. The primary study objectives were to evaluate the safety, feasibility, and efficacy of the LAAE concomitant with LIS LVAD. RESULTS: Preoperative characteristics of patients in the Non-LAAE and LAAE groups were similar. LAAE was successfully excluded in all prospective patients (100%). Primary safety endpoints of chest tube output within the first 24 postoperative hours, Reoperation for bleeding within 48 h, and index hospitalization mortality demonstrated comparable safety of LAAE versus Non-LAAE with LIS LVAD. Cox proportional hazard regression demonstrated that LAAE with LIS LVAD was associated with 37% and 49% reduction in the risk of stroke and disabling stroke, respectively (p > .05). CONCLUSION: Results from our pilot study demonstrated the safety and feasibility of LAAE concomitant with LIS LVAD as a stroke prevention strategy. This is the first prospective study describing LAAE performed concomitantly to less invasive LVAD implantation. The efficacy of LAAE in long-term stroke prevention needs to be confirmed in future prospective randomized clinical trials.

Impact of surgical approach for left ventricular assist device implantation on postoperative invasive hemodynamics and right ventricular failure.

BACKGROUND: Right ventricular failure (RVF) remains one of the major causes of morbidity and mortality after left ventricular assist device (LVAD) implantation. We sought to compare immediate postoperative invasive hemodynamics and the risk of RVF following two different surgical approaches: less invasive surgery (LIS) versus full sternotomy (FS). METHODS: The study population comprised all 231 patients who underwent implantation of a HeartMate 3 (Abbott) LVAD at our institution from 2015 to 2020, utilizing an LIS (n = 161; 70%) versus FS (n = 70; 30%) surgical approach. Outcomes included postoperative invasive hemodynamic parameters, vasoactive-inotropic score (VIS), RVF during index hospitalization, and 6-month mortality. RESULTS: Baseline clinical characteristics of the two groups were similar. Multivariate analysis showed that LIS, compared with FS, was associated with the improved cardiac index (CI) at the sixth postoperative hour (p = .036) and similar CI at 24 h, maintained by lower VIS at both timepoints (p = .002). The LIS versus FS approach was also associated with a three-fold lower incidence of in-hospital severe RVF (8.7% vs. 28.6%, p < .001) and need for RVAD support (5.0% vs. 17.1%, p = .003), and with 68% reduction in the risk of 6-month mortality after LVAD implantation (Hazard ratio, 0.32; CI, 0.13-0.78; p = .012). CONCLUSION: Our findings suggest that LIS, compared with FS, is associated with a more favorable hemodynamic profile, as indicated by similar hemodynamic parameters maintained by lower vasoactive-inotropic support during the acute postoperative period. These findings were followed by a reduction in the risk of severe RVF and 6-month mortality in the LIS group.

Association Between the COVID-19 Pandemic and Disparities in Access to Major Surgery in the US.

Importance: Racial minority groups account for 70% of excess deaths not related to COVID-19. Understanding the association of the Centers for Medicare & Medicaid Services' (CMS's) moratorium delaying nonessential operations with racial disparities will help shape future pandemic responses. Objective: To evaluate the association of the CMS's moratorium on elective operations during the first wave of the COVID-19 pandemic among Black individuals, Asian individuals, and individuals of other races compared with White individuals. Design, Setting, and Participants: This cross-sectional study assessed a 719-hospital retrospective cohort of 3 470 905 adult inpatient hospitalizations for major surgery between January 1, 2018, and October 31, 2020. Exposure: The first wave of COVID-19 infections between March 1, 2020, and May 31, 2020. Main Outcomes and Measures: The main outcome was the association between changes in monthly elective surgical case volumes and the first wave of COVID-19 infections as a function of patient race, evaluated using negative binomial regression analysis. Results: Among 3 470 905 adults (1 823 816 female [52.5%]) with inpatient hospitalizations for major surgery, 70 752 (2.0%) were Asian, 453 428 (13.1%) were Black, 2 696 929 (77.7%) were White, and 249 796 (7.2%) were individuals of other races. The number of monthly elective cases during the first wave was 49% (incident rate ratio [IRR], 0.49; 95% CI, 0.486-0.492; P < .001) compared with the baseline period. The relative reduction in unadjusted elective surgery cases for Black (unadjusted IRR, 0.99; 95% CI, 0.97-1.01; P = .36), Asian (unadjusted IRR, 1.08; 95% CI, 1.03-1.14; P = .001), and other race individuals (unadjusted IRR, 0.97; 95% CI, 0.95-1.00; P = .05) during the surge period compared with the baseline period was very close to the change in cases for White individuals. After adjustment for age, sex, comorbidities, and surgical procedure, there was still no evidence that the first wave of the pandemic was associated with disparities in access to elective surgery. Conclusions and Relevance: In this cross-sectional study, the CMS's moratorium on nonessential operations was associated with a 51% reduction in elective operations. It was not associated with greater reductions in operations for racial minority individuals than for White individuals. This evidence suggests that the early response to the pandemic did not increase disparities in access to surgical care.

Left Ventricular Assist Device Support-Induced Alteration of Mechanical Stress on Aortic Valve and Aortic Wall.

The aim of this study was to evaluate the fluid dynamics in the aortic valve and proximal aorta during continuous-flow left ventricular assist device (LVAD) support using epiaortic echocardiography and vector flow mapping technology. A total of 12 patients who underwent HeartMate 3 implantation between December 2018 and February 2020 were prospectively examined. The wall shear stress (WSS) on the ascending aorta, aortic root, and aortic valve was evaluated before and after LVAD implantation. The median age of the cohort was 62 years and 17% were women. The peak WSS on the ascending aorta (Pre 1.48 [0.86-1.69] [Pascal {Pa}] vs. Post 0.33 [0.21-0.58] [Pa]; p = 0.002), aortic root (Pre 0.46 [0.31-0.58] (Pa) vs. Post 0.18 [0.12-0.25] (Pa); p = 0.001), and ventricularis of the aortic valve (Pre 1.76 [1.59-2.30] (Pa) vs. Post 0.30 [0.10-0.61] (Pa); p = 0.001) was significantly lower after LVAD implantation. No difference in WSS was observed on the fibrosa of the aortic valve (Pre 0.36 [0.22-0.53] (Pa) vs. Post 0.38 [0.38-0.52] (Pa); p = 0.850) before and after implantation. The WSS on the ascending aorta, aortic root, and ventricularis of the aortic valve leaflets was significantly altered by LVAD implantation, providing preliminary data on the potential contribution of fluid dynamics to LVAD-induced aortic insufficiency and root thrombus.

Influence of aneurysmal aortic root geometry on mechanical stress to the aortic valve leaflet.

AIMS: While mechanical stress caused by blood flow, e.g. wall shear stress (WSS), and related parameters, e.g. oscillatory shear index (OSI), are increasingly being recognized as key moderators of various cardiovascular diseases, studies on valves have been limited because of a lack of appropriate imaging modalities. We investigated the influence of aortic root geometry on WSS and OSI on the aortic valve (AV) leaflet. METHODS AND RESULTS: We applied our novel approach of intraoperative epi-aortic echocardiogram to measure the haemodynamic parameters of WSS and OSI on the AV leaflet. Thirty-six patients were included, which included those who underwent valve-sparing aortic root replacement (VSARR) with no significant aortic regurgitation (n = 17) and coronary artery bypass graft (CABG) with normal AV (n = 19). At baseline, those who underwent VSARR had a higher systolic WSS (0.52 ± 0.12 vs. 0.32 ± 0.08 Pa, respectively, P < 0.001) and a higher OSI (0.37 ± 0.06 vs. 0.29 ± 0.04, respectively, P < 0.001) on the aortic side of the AV leaflet than those who underwent CABG. Multivariate regression analysis revealed that the size of the sinus of Valsalva had a significant association with WSS and OSI. Following VSARR, WSS and OSI values decreased significantly compared with the baseline values (WSS: 0.29 ± 0.12 Pa, P < 0.001; OSI: 0.26 ± 0.09, P < 0.001), and became comparable to the values in those who underwent CABG (WSS, P = 0.42; OSI, P = 0.15). CONCLUSIONS: Mechanical stress on the AV gets altered in correlation with the size of the aortic root. An aneurysmal aortic root may expose the leaflet to abnormal fluid dynamics. The VSARR procedure appeared to reduce these abnormalities.