Transcatheter aortic valve replacement outcomes in patients with low-flow very low-gradient aortic stenosis.

AIMS: In patients with severe aortic stenosis (AS), low-flow low-gradient (LG) is a known predictor of worse outcomes. However, very LG may represent a distinct population with further cardiac dysfunction. It is unknown whether this population benefits from transcatheter aortic valve replacement (TAVR). We aimed to describe the patient characteristics and clinical outcomes of low-flow very LG severe AS. METHODS AND RESULTS: This single-centre study included all patients with low-flow severe AS between 2019 and 2021. Patients were divided into groups with very LG [mean pressure gradient (MPG) ≤ 20 mmHg], LG (20 < MPG < 40 mmHg), and high-gradient (HG) (MPG ≥ 40 mmHg). Composite endpoint of all-cause mortality and heart failure rehospitalization was compared. A total of 662 patients [very LG 130 (20%); LG 339 (51%); HG 193 (29%)] were included. Median follow-up was 12 months. Very LG cohort had a higher prevalence of comorbid conditions with lower left ventricular ejection fraction (45% vs. 57% vs. 60%; P < 0.001). There was a graded increase in the risk of composite endpoint in the lower MPG strata (P < 0.001). Among those who underwent TAVR, very LG was an independent predictor of the composite endpoint (adjusted HR 2.42 [1.29-4.55]). While LG and HG cohorts had decreased risk of composite endpoint after TAVR compared with conservative management, very LG was not associated with risk reduction (adjusted HR 0.69 [0.35-1.34]). CONCLUSION: Low-flow very LG severe AS represents a distinct population with significant comorbidities and worse outcomes. Further studies are needed to evaluate the short- and long-term benefits of TAVR in this population.

Prognostic Implication of Pulmonary Hypertension in Low-Flow Low-Gradient Aortic Stenosis After Transcatheter Aortic Valve Replacement.

Prognostic implications of pulmonary hypertension (PH) in low-flow low-gradient (LG) aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR) remains unexplored. We aimed to investigate the impact of baseline and changes in PH after TAVR. In this single-center retrospective study, we included patients who underwent TAVR for low-flow LG AS. Patients were categorized into 2 groups: baseline pulmonary artery systolic pressure (PASP) <46 mm Hg (no-to-mild PH) and PASP ≥46 mm Hg (moderate-to-severe PH). On the basis of changes in PASP after TAVR, patients were stratified into increased (ΔPASP ≥ + 5 mm Hg), no change (-4 to +4 mm Hg), and decreased (≤ -5 mm Hg) groups. Primary end point was a composite of all-cause mortality and heart failure rehospitalization. In total, 210 patients were included, 148 in the no-to-mild PH group and 62 in the moderate-to-severe PH group. Median follow-up was 13.2 months. The moderate-to-severe PH group was at an increased risk of composite end point (adjusted hazard ratio [HR] 3.5, 95% confidence interval [CI] 1.8 to 6.9), all-cause mortality (HR 2.4, 95% CI 1.1 to 5.6), and heart failure rehospitalization (HR 8.3, 95% CI 2.9 to 23.7). There were no differences in clinical outcomes among those with increased (32%), no change (28%), and decreased (39%) PASP after TAVR. In conclusion, moderate-to-severe PH at baseline is an independent predictor of worse clinical outcomes in patients with low-flow LG AS who undergo TAVR, and this cohort of patients do not seem to derive the benefits of postoperative reduction of PASP.

The Relationship Between Social Determinants of Health and Racial Disparities in COVID-19 Mortality.

BACKGROUND: The COVID-19 pandemic has magnified existing health disparities for marginalized populations in the United States (U.S.), particularly among Black Americans. Social determinants of health are powerful drivers of health outcomes that could influence COVID-19 racial disparities. METHODS: We collected data from publicly available databases on COVID-19 death rates through October 28, 2020, clinical covariates, and social determinants of health indicators at the U.S. county level. We utilized negative binomial regression to assess the association between social determinants of health and COVID-19 mortality focusing on racial disparities in mortality. RESULTS: Counties with higher death rates had a higher proportion of Black residents and greater levels of adverse social determinants of health. A one percentage point increase in percent Black residents, percent uninsured adults, percent low birthweight, percent adults without high school diploma, incarceration rate, and percent households without internet in a county increased COVID-19 death rates by 0.9% (95% CI 0.5%-1.3%), 1.9% (95% CI 1.1%-2.7%), 7.6% (95% CI 4.4%-11.0%), 3.5% (95% CI 2.5%-4.5%), 5.4% (95% CI 1.3%-9.7%), and 3.4% (95% CI 2.5%-4.2%), respectively. Counties in the lowest quintile of a measure of economic privilege had an increased COVID-19 death rates of 67.5% (95% CI 35.9%-106.6%). Multivariate regression and subgroup analyses suggested that adverse social determinants of health may partially explain racial disparities in COVID-19 mortality. CONCLUSIONS: This study demonstrates that social determinants of health contribute to COVID-19 mortality for Black Americans at the county level, highlighting the need for public health policies that address racial disparities in health outcomes.

Strategies to reduce the impact of demand for concurrent endovascular thrombectomy.

BACKGROUND: The rise in demand for endovascular thrombectomy (EVT) has increased the possibility that multiple patients with acute ischemic stroke may present concurrently and exceed local capacity to provide timely treatment. In this work, we quantitatively compared the efficacy of various strategies to mitigate demand in excess of capacity (DEC). METHODS: Strategies evaluated included a backup neurointerventional team for 3 hours, 8 hours, or 24 hours per day; a separate pre-intervention imaging team; and a 30% decrease in procedure duration. For each strategy, empirical distributions were used to probabilistically generate arrival time and case duration for 16 000 independent trials repeated across a range of annual case volumes. DEC was calculated from time series representing the number of concurrent cases at each minute of the year for each trial at each case volume. RESULTS: All strategies decreased DEC compared with baseline. At a representative volume of 250 cases per year, availability of a backup team for 3 hours, 8 hours, and 24 hours per day reduced DEC by 27.0%, 60.3%, and 97.2%, respectively, compared with baseline. Similarly, availability of a pre-intervention imaging team and a 30% decrease in procedure duration reduced DEC by 26.6% and 17.7%, respectively, compared with baseline. CONCLUSIONS: A backup neurointerventional team, even if available only part time, was an effective strategy for decreasing DEC for EVT. Understanding the actual quantitative benefit of each strategy can facilitate rational cost-benefit analyses underlying the development of efficient and sustainable models of care.

Simultaneous patient presentation for endovascular thrombectomy in acute ischemic stroke.

BACKGROUND: Increased demand for endovascular thrombectomy has increased the likelihood of simultaneous patient presentation leading to competing demand for time-critical treatment that could adversely impact patient outcomes. We aimed to quantify the occurrence of simultaneous patient presentation at different patient volumes. METHODS: Empirical distributions for time of patient presentation and case duration were used to probabilistically generate arrival time and case duration for a set annual patient volume, ranging from 1 to 500 cases per year, for 16 000 independent trials at each volume. Time series were generated for each trial to represent the number of cases being performed at each minute of the year. Time series were used to calculate daily thrombectomy demand, annual concurrent demand, and hourly excess demand. RESULTS: The patient volumes at which at least one annual occurrence of concurrent demand by two patients was 50% and 97.5% likely were 45 and 101, respectively. The volumes at which at least one annual occurrence of concurrent demand by three patients was 50% and 97.5% likely were 216 and 387, respectively. There was dramatic variation in the occurrence of excess demand by two or more patients throughout the day. CONCLUSIONS: The occurrence of simultaneous presentation by multiple patients for endovascular thrombectomy varies with annual patient volume and time of day. Understanding these trends and the associated patient impact can inform intelligent strategies at regional and national levels for optimizing patient care within real-world financial and operational constraints.

Macrocyclization in the Design of Organic n-Type Electronic Materials.

Here, we compare analogous cyclic and acyclic π-conjugated molecules as n-type electronic materials and find that the cyclic molecules have numerous benefits in organic photovoltaics. This is the first report of such a direct comparison. We designed two conjugated cycles for this study. Each comprises four subunits: one combines four electron-accepting, redox-active, diphenyl-perylenediimide subunits, and the other alternates two electron-donating bithiophene units with two diphenyl-perylenediimide units. We compare the macrocycles to acyclic versions of these molecules and find that, relative to the acyclic analogs, the conjugated macrocycles have bathochromically shifted UV-vis absorbances and are more easily reduced. In blended films, macrocycle-based devices show higher electron mobility and good morphology. All of these factors contribute to the more than doubling of the power conversion efficiency observed in organic photovoltaic devices with these macrocycles as the n-type, electron transporting material. This study highlights the importance of geometric design in creating new molecular semiconductors. The ease with which we can design and tune the electronic properties of these cyclic structures charts a clear path to creating a new family of cyclic, conjugated molecules as electron transporting materials in optoelectronic and electronic devices.