Dysregulated platelet function in patients with postacute sequelae of COVID-19.

BACKGROUND: Postacute sequelae of COVID-19 (PASC), also referred to as "Long COVID", sometimes follows COVID-19, a disease caused by SARS-CoV-2. Although SARS-CoV-2 is well known to promote a prothrombotic state, less is known about the thrombosis risk in PASC. Our objective was to evaluate platelet function and thrombotic potential in patients following recovery from SARS-CoV-2, but with clear symptoms of patients with PASC. METHODS: patients with PASC and matched healthy controls were enrolled in the study on average 15 months after documented SARS-CoV-2 infection. Platelet activation was evaluated by light transmission aggregometry (LTA) and flow cytometry in response to platelet surface receptor agonists. Thrombosis in platelet-deplete plasma was evaluated by Factor Xa activity. A microfluidics system assessed thrombosis in whole blood under shear stress conditions. RESULTS: A mild increase in platelet aggregation in patients with PASC through the thromboxane receptor was observed, and platelet activation through the glycoprotein VI (GPVI) receptor was decreased in patients with PASC compared to age- and sex-matched healthy controls. Thrombosis under shear conditions as well as Factor Xa activity were reduced in patients with PASC. Plasma from patients with PASC was an extremely potent activator of washed, healthy platelets - a phenomenon not observed when stimulating healthy platelets after incubation with plasma from healthy individuals. CONCLUSIONS: patients with PASC show dysregulated responses in platelets and coagulation in plasma, likely caused by a circulating molecule that promotes thrombosis. A hitherto undescribed protective response appears to exist in patients with PASC to counterbalance ongoing thrombosis that is common to SARS-CoV-2 infection.

Ninety-Day Risk-Standardized Home Time as a Performance Metric for Cardiac Surgery Hospitals in the United States.

BACKGROUND: Assessing hospital performance for cardiac surgery necessitates consistent and valid care quality metrics. The association of hospital-level risk-standardized home time for cardiac surgeries with other performance metrics such as mortality rate, readmission rate, and annual surgical volume has not been evaluated previously. METHODS: The study included Medicare beneficiaries who underwent isolated or concomitant coronary artery bypass graft, aortic valve, or mitral valve surgery from January 1, 2013, to October 1, 2019. Hospital-level performance metrics of annual surgical volume, 90-day risk-standardized mortality rate, 90-day risk-standardized readmission rate, and 90-day risk-standardized home time were estimated starting from the day of surgery using generalized linear mixed models with a random intercept for the hospital. Correlations between the performance metrics were assessed using the Pearson correlation coefficient. Patient-level clinical outcomes were also compared across hospital quartiles by 90-day risk-standardized home time. Last, the temporal stability of performance metrics for each hospital during the study years was also assessed. RESULTS: Overall, 919 698 patients (age 74.2±5.8 years, 32% women) were included from 1179 hospitals. Median 90-day risk-standardized home time was 71.2 days (25th-75th percentile, 66.5-75.6), 90-day risk-standardized readmission rate was 26.0% (19.5%-35.7%), and 90-day risk-standardized mortality rate was 6.0% (4.0%-8.8%). Across 90-day home time quartiles, a graded decline was observed in the rates of in-hospital, 90-day, and 1-year mortality, and 90-day and 1-year readmission. Ninety-day home time had a significant positive correlation with annual surgical volume (r=0.31; P<0.001) and inverse correlation with 90-day risk-standardized readmission rate (r=-0.40; P <0.001) and 90-day risk-standardized mortality rate (r=-0.60; P <0.001). Use of 90-day home time as a performance metric resulted in a meaningful reclassification in performance ranking of 22.8% hospitals compared with annual surgical volume, 11.6% compared with 90-day risk-standardized mortality rate, and 19.9% compared with 90-day risk-standardized readmission rate. Across the 7 years of the study period, 90-day home time demonstrated the most temporal stability of the hospital performance metrics. CONCLUSIONS: Ninety-day risk-standardized home time is a feasible, comprehensive, patient-centered metric to assess hospital-level performance in cardiac surgery with greater temporal stability than mortality and readmission measures.

Five-Year Outcomes of Transcatheter or Surgical Aortic-Valve Replacement.

BACKGROUND: There are scant data on long-term clinical outcomes and bioprosthetic-valve function after transcatheter aortic-valve replacement (TAVR) as compared with surgical aortic-valve replacement in patients with severe aortic stenosis and intermediate surgical risk. METHODS: We enrolled 2032 intermediate-risk patients with severe, symptomatic aortic stenosis at 57 centers. Patients were stratified according to intended transfemoral or transthoracic access (76.3% and 23.7%, respectively) and were randomly assigned to undergo either TAVR or surgical replacement. Clinical, echocardiographic, and health-status outcomes were followed for 5 years. The primary end point was death from any cause or disabling stroke. RESULTS: At 5 years, there was no significant difference in the incidence of death from any cause or disabling stroke between the TAVR group and the surgery group (47.9% and 43.4%, respectively; hazard ratio, 1.09; 95% confidence interval [CI], 0.95 to 1.25; P = 0.21). Results were similar for the transfemoral-access cohort (44.5% and 42.0%, respectively; hazard ratio, 1.02; 95% CI, 0.87 to 1.20), but the incidence of death or disabling stroke was higher after TAVR than after surgery in the transthoracic-access cohort (59.3% vs. 48.3%; hazard ratio, 1.32; 95% CI, 1.02 to 1.71). At 5 years, more patients in the TAVR group than in the surgery group had at least mild paravalvular aortic regurgitation (33.3% vs. 6.3%). Repeat hospitalizations were more frequent after TAVR than after surgery (33.3% vs. 25.2%), as were aortic-valve reinterventions (3.2% vs. 0.8%). Improvement in health status at 5 years was similar for TAVR and surgery. CONCLUSIONS: Among patients with aortic stenosis who were at intermediate surgical risk, there was no significant difference in the incidence of death or disabling stroke at 5 years after TAVR as compared with surgical aortic-valve replacement. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).

Clinical and echocardiographic outcomes with new-onset left bundle branch block after SAPIEN-3 transcatheter aortic valve replacement.

BACKGROUND: New-onset left bundle branch block (LBBB) can develop after transcatheter aortic valve replacement (TAVR) resulting in worse outcomes. AIMS: Describe clinical and echocardiographic outcomes with new-onset LBBB after TAVR. METHODS: We included consecutive patients who underwent transfemoral-TAVR with SAPIEN-3 (S3) valve between April 2015 and December 2018. Exclusion criteria included pre-existing LBBB, right BBB, left anterior hemiblock, left posterior hemiblock, wide QRS ≥ 120ms, prior permanent pacemaker (PPM), and nontransfemoral access. RESULTS: Among 612 patients, 11.4% developed new-onset LBBB upon discharge. The length of stay was longer with new-onset LBBB compared with no LBBB [3 (2-5) days versus 2 (1-3) days; p < 0.001]. New-onset LBBB was associated with higher rates of 30-day PPM requirement (18.6% vs. 5.4%; p < 0.001) and 1-year heart failure hospitalizations (10.7% vs. 4.4%; p = 0.033). There was no difference in 3-year mortality between both groups (30.9% vs. 30.6%; p = 0.829). Further, new-onset LBBB was associated with lower left ventricular ejection fraction (LVEF) at both 30 days (55.9 ± 11.4% vs. 59.3 ± 9%; p = 0.026) and 1 year (55 ± 12% vs. 60.1 ± 8.9%; p = 0.002). These changes were still present when we stratified patients according to baseline LVEF (≥50% or <50%). New-onset LBBBs were associated with a higher 1-year LV end-diastolic volume index (51.4 ± 18.6 vs. 46.4 ± 15.1 ml/m2 ; p = 0.036), and LV end-systolic volume index (23.2 ± 14.1 vs. 18.9 ± 9.7 ml/m2 ; p = 0.009). Compared with resolved new-onset LBBB, persistent new-onset LBBB was associated with worse LVEF and higher PPM at 1 year. CONCLUSIONS: New-onset LBBB after S3 TAVR was associated with higher PPM requirement, worse LVEF, higher LV volumes, and increased heart failure hospitalizations, with no difference in mortality.

Thrombotic outcomes in patients in a large clinical enterprise following COVID-19 vaccination.

Vaccination against COVID-19 reduces infection-related mortality. Unfortunately, reports of vaccine-induced immune thrombotic thrombocytopenia (VITT) in individuals administered adenovirus-vector-based vaccines (ChAdOx1 nCoV-19 and Ad26.COV2.S) have spurred side effect concerns. To address vaccine hesitancy related to this, it is essential to determine the incidence of VITT (defined by a 50% decrease in platelet count and positive anti-PF4 immunoassay within 4-28 days after vaccination) among patients administered two doses of an mRNA-based COVID-19 vaccination. We identified a retrospective cohort of 223,345 patients in the Cleveland Clinic Enterprise administered a COVID-19 vaccine at any location in Northeast Ohio and Florida from 12/4/2020 to 6/6/2021. 97.3% of these patients received an mRNA-based vaccination. Patients with: (1) a serial complete blood count both before and after vaccination and (2) a decrease in platelet count of ≥ 50% were selected for chart review. The primary outcome was the incidence of thrombotic events, including venous thromboembolism (VTE) and arterial thrombosis, 4-28 days post vaccination. Of 74 cohort patients with acute thrombosis, 72 (97.3%) demonstrated clear etiologies, such as active malignancy. Of two patients with unprovoked thrombosis, only one had findings concerning for VITT, with a strongly positive anti-PF4 antibody assay. In this large, multi-state, retrospective cohort, of 223,345 patients (97.2% of whom received the mRNA-based mRNA-1273 or BNT162b2 vaccines), we detected a single case that was concerning for VITT in a patient who received an mRNA vaccine. The overwhelming majority of patients with a thrombotic event 4-28 days following vaccination demonstrated clear etiologies.

Prognostic impact of left ventricular systolic dysfunction in patients with mixed aortic valve disease undergoing aortic valve replacement.

BACKGROUND: The implications of left ventricular remodeling and dysfunction before and after aortic valve replacement (AVR) for mixed aortic valve disease (MAVD) are not well understood. This study aims to evaluate the impact of AVR on left ventricular (LV) systolic function in MAVD, and determine the prognostic value of postoperative LV global longitudinal strain (LV-GLS) and LV ejection fraction (LVEF). METHODS: We retrospectively assessed 489 consecutive patients with MAVD (defined as at least moderate aortic stenosis and at least moderate aortic regurgitation) and baseline LVEF ≥50%, who underwent AVR between February 2003 and August 2018. All patients had baseline echocardiography, whereas 192 patients underwent postoperative echocardiography between 3 and 18 months after AVR. The primary endpoint was all-cause mortality. RESULTS: Mean age was 65 ± 15 years, and 65% were male. AVR in MAVD patients has a neutral effect on LV systolic function quantitated by LVEF and LV-GLS. During a median follow-up period of 5.8 years, 65 patients (34%) of 192 patients with follow-up echocardiography died. The patients with postoperative LVEF ≥50% had better survival than those with postoperative LVEF <50% (P < .001). Furthermore, among patients with postoperative LVEF ≥50%, mortality differed between patients with postoperative LV-GLS worse than -15% and those with postoperative LV-GLS better than -15% (P < .001). CONCLUSIONS: In patients with MAVD who underwent AVR, the mean postoperative LV-GLS and LVEF remain at a similar value to baseline. However, worse postoperative LV-GLS and LVEF were both independently associated with higher mortality in this population.

Cryptic species in a colorful genus: Integrative taxonomy of the bush robins (Aves, Muscicapidae, Tarsiger) suggests two overlooked species.

Several cryptic avian species have been validated by recent integrative taxonomic efforts in the Sino-Himalayan mountains, indicating that avian diversity in this global biodiversity hotspot may be underestimated. In the present study, we investigated species limits in the genus Tarsiger, the bush robins, a group of montane forest specialists with high species richness in the Sino-Himalayan region. Based on comprehensive sampling of all 11 subspecies of the six currently recognized species, we applied an integrative taxonomic approach by combining multilocus, acoustic, plumage and morphometric analyses. Our results reveal that the isolated north-central Chinese populations of Tarsiger cyanurus, described as the subspecies albocoeruleus but usually considered invalid, is distinctive in genetics and vocalisation, but only marginally differentiated in morphology. We also found the Taiwan endemic T. indicus formosanus to be distinctive in genetics, song and morphology from T. i. indicus and T. i. yunnanensis of the Sino-Himalayan mountains. Moreover, Bayesian species delimitation using BPP suggests that both albocoeruleus and formosanus merit full species status. We propose their treatment as 'Qilian Bluetail' T. albocoeruleus and 'Taiwan Bush Robin' T. formosanus, respectively.

Association of hospital procedural volume with incidence and outcomes of surgical bailout in patients undergoing transcatheter aortic valve replacement.

OBJECTIVES: This study sought to examine the association of hospital procedural volume with the incidence and outcomes of surgical bailout (SB) in patients who undergo transcatheter aortic valve replacement (TAVR). BACKGROUND: SB is required for serious complications during or after TAVR. It remains unclear whether hospital experiences affect the incidence and outcomes of SB. METHODS: We retrospectively identified patients who underwent endovascular TAVR using the Nationwide Readmissions Database 2012-2017. We examined the association of annual hospital procedural volume (annual number of endovascular TAVR cases in each hospital in each year) with the incidence and in-hospital mortality of SB using multivariable logistic regressions and restricted cubic splines. RESULTS: Among 82,764 eligible patients, the incidence of SB was 0.95% (n = 789) and decreased from 2012 to 2017 (from 2.66% to 0.49%; Ptrend < 0.001), while in-hospital mortality of SB remained high over years (from 26.0% to 23.5%; Ptrend  = 0.773). Very-high-volume hospitals (≥200 cases/year), as compared with low-volume hospitals (≤49 cases/year), showed significantly a lower incidence of SB (0.49% vs. 1.81%; adjusted OR = 0.28, 95% CI = 0.21-0.38), but similar in-hospital mortality of SB (26.2% vs. 25.6%; adjusted OR = 0.88, 95% CI = 0.47-1.66). There was a significant nonlinear, inverse association of hospital volume with the incidence of SB, but not with the in-hospital mortality of SB. CONCLUSIONS: Hospitals with higher TAVR volumes have a lower risk of SB, but the in-hospital mortality after SB does not change with hospital TAVR volume. Our findings highlight the importance that physicians should always be aware of the high mortality risk of SB following TAVR regardless of hospital procedural experiences.

Two-year outcomes after transcatheter aortic valve-in-valve implantation in degenerated surgical valves.

BACKGROUND: Transcatheter aortic valve-in-valve implantation (ViV-TAVI) has emerged in recent years as a safe alternative to redo surgery in high-risk patients. Although early results are encouraging, data beyond short-term outcomes are lacking. Herein, we aimed to assess the 2-year outcomes after ViV-TAVI. METHODS: Patients undergoing ViV-TAVI for degenerated surgical valves between 2013 and 2019 at the Cleveland Clinic were reviewed. The coprimary endpoints were all-cause mortality and congestive heart failure (CHF) hospitalizations. We used time-to-event analyses to assess the primary outcomes. Further, we measured the changes in transvalvular gradients and the incidence of structural valve deterioration (SVD). RESULTS: One hundred and eighty-eight patients were studied (mean age = 76 years; 65% males). At 2 years of follow-up, all-cause mortality and CHF hospitalizations occurred in 15 (8%) and 28 (14.9%) patients, respectively. On multivariable analysis, the postprocedural length of stay was a significant predictor for both all-cause mortality (hazard ratio [HR] = 1.1; 95% confidence interval [CI]: 1.01, 1.19) and CHF hospitalization (HR = 1.16; 95% CI: 1.07, 1.27). However, the internal diameter of the surgical valve was not associated with significant differences in both primary endpoints. For hemodynamic outcomes, nine patients (4.8%) developed SVD. The mean and peak transvalvular pressure gradients remained stable over the follow-up period. CONCLUSION: ViV-TAVI for degenerated surgical valves was associated with favorable 2-year clinical and hemodynamic outcomes. Further studies are needed to better understand the role of ViV-TAVI as a treatment option in the life management of aortic valve disease.

Incidence, treatment, and outcomes of acute myocardial infarction following transcatheter or surgical aortic valve replacement.

OBJECTIVES: This study aimed to evaluate the incidence, treatment, and outcomes of acute myocardial infarction (AMI) following transcatheter or surgical aortic valve replacement (TAVR or SAVR). BACKGROUND: Coronary artery disease is common in patients who undergo aortic valve replacement. However, little is known about differences in clinical features of post-TAVR or post-SAVR AMI. METHODS: We retrospectively identified post-TAVR or post-SAVR (including isolated and complex SAVR) patients admitted with AMI using the Nationwide Readmissions Database 2012-2017. Incidence, invasive strategy (coronary angiography or revascularization), and in-hospital outcomes were compared between post-TAVR and post-SAVR AMIs. RESULTS: The incidence of 180-day AMI was higher post-TAVR than post-SAVR (1.59% vs. 0.72%; p < 0.001). Post-TAVR AMI patients (n = 1315), compared with post-SAVR AMI patients (n = 1344), were older, had more comorbidities and more frequent non-ST-elevation AMI (NSTEMI: 86.6% vs. 78.0%; p < 0.001). After propensity-score matching, there was no significant difference in in-hospital mortality between post-TAVR and post-SAVR AMIs (14.7% vs. 16.1%; p = 0.531), but the mortality was high in both groups, particularly in ST-elevation AMI (STEMI: 38.8% vs. 29.2%; p = 0.153). Invasive strategy was used less frequently for post-TAVR AMI than post-SAVR AMI (25.6% vs. 38.3%; p < 0.001). Invasive strategy was associated with lower mortality in both post-TAVR (adjusted odds ratio = 0.40; 95% confidence interval = [0.24-0.66]) and post-SAVR groups (0.60 [0.41-0.88]). CONCLUSIONS: AMI, albeit uncommon, was more frequent post-TAVR than post-SAVR. Patients commonly presented with NSTEMI, but the mortality of STEMI was markedly high. Further studies are needed to understand why a substantial percentage of patients do not receive invasive coronary treatment, particularly after TAVR, despite seemingly better outcomes with invasive strategy.

Sex-based differences in left ventricular remodeling in patients with chronic aortic regurgitation: a multi-modality study.

BACKGROUND: Significant aortic regurgitation (AR) leads to left ventricular (LV) remodeling; however, little data exist regarding sex-based differences in LV remodeling in this setting. We sought to compare LV remodeling and AR severity, assessed by echocardiography and cardiovascular magnetic resonance (CMR), to discern sex-based differences. METHODS: Patients with ≥ moderate chronic AR by echocardiography who underwent CMR within 90 days between December 2005 and October 2015 were included. Nonlinear regression models were built to assess the effect of AR regurgitant fraction (RF) on LV remodeling. A generalized linear model and Bland Altman analyses were constructed to evaluate differences between CMR and echocardiography. Referral for surgical intervention based on symptoms and LV remodeling was evaluated. RESULTS: Of the 243 patients (48.3 ± 16.6 years, 58 (24%) female), 119 (49%) underwent surgical intervention with a primary indication of severe AR, 97 (82%) men, 22 (18%) women. Significant sex differences in LV remodeling emerged on CMR. Women demonstrated significantly smaller LV end-diastolic volume index (LVEDVI) (96.8 ml/m2 vs 125.6 ml/m2, p < 0.001), LV end-systolic volume index (LVESVI) (41.1 vs 54.5 ml/m2, p < 0.001), blunted LV dilation in the setting of increasing AR severity (LVEDVI p value < 0.001, LVESVI p value 0.011), and LV length indexed (8.32 vs 9.69 cm, p < 0.001). On Bland Altman analysis, a significant interaction with sex and LV diameters was evident, demonstrating a significant increase in the difference between CMR and echocardiography measurements as the LV enlarged in women: LVEDVI (p = 0.006), LVESVI (p < 0.001), such that echocardiographic measurements increasingly underestimated LV diameters in women as the LV enlarged. LV length was higher for males with a linear effect from RF (p < 0.001), with LV length increasing at a higher rate with increasing RF for males compared to females (two-way interaction with sex p = 0.005). Sphericity volume index was higher for men after adjusting for a relative wall thickness (p = 0.033). CONCLUSIONS: CMR assessment of chronic AR revealed significant sex differences in LV remodeling and significant echocardiographic underestimation of LV dilation, particularly in women. Defining optimal sex-based CMR thresholds for surgical referral should be further developed. TRIAL REGISTRATION: NA.

Emergency cardiac surgery in patients on oral anticoagulants and antiplatelet medications.

BACKGROUND: Emergency surgery, blood transfusion, and reoperation for bleeding have been associated with increased operative morbidity and mortality. The recent increased use of direct oral anticoagulants and antiplatelet medications has made the above more challenging. In addition, cardiopulmonary bypass (CPB), with its associated hemodilution, fibrinolysis, and platelet consumption, may exacerbate the pre-existing coagulopathy and increase the risk of bleeding. AIM: The aim of this study was to examine available literature with regard to treating patients who are on the above medications and require emergency cardiac surgery. RESULTS: Management decisions are typically made on a case-by-case basis. Surgery is delayed when possible, and less invasive percutaneous options should be considered if feasible. Attention is paid to exercising meticulous techniques, avoiding excessive hypothermia, and treating coexisting issues such as sepsis. Ensuring a dry operative field upon entry by correcting the coagulopathy with reversal agents is offset by the concern of potentially hindering efforts to anticoagulate the patient (heparin resistance) in preparation for CPB, in addition to possibly increasing the risk of thromboembolism. CONCLUSION: Proper knowledge of anticoagulants, their reversal agents, and the usefulness of laboratory testing are all essential. Platelet transfusion remains the mainstay for antiplatelet medications. Four-factor prothrombin complex concentrate is considered in patients on oral anticoagulants if CPB needs to be instituted quickly. Specific reversal agents such as idarucizumab and andexanet alfa can be considered if significant tissue dissection is anticipated, such as redo sternotomy, but are costly and may lead to heparin resistance and anticoagulant rebound.

Cardiac risk stratification in cancer patients: A longitudinal patient-patient network analysis.

BACKGROUND: Cardiovascular disease is a leading cause of death in general population and the second leading cause of mortality and morbidity in cancer survivors after recurrent malignancy in the United States. The growing awareness of cancer therapy-related cardiac dysfunction (CTRCD) has led to an emerging field of cardio-oncology; yet, there is limited knowledge on how to predict which patients will experience adverse cardiac outcomes. We aimed to perform unbiased cardiac risk stratification for cancer patients using our large-scale, institutional electronic medical records. METHODS AND FINDINGS: We built a large longitudinal (up to 22 years' follow-up from March 1997 to January 2019) cardio-oncology cohort having 4,632 cancer patients in Cleveland Clinic with 5 diagnosed cardiac outcomes: atrial fibrillation, coronary artery disease, heart failure, myocardial infarction, and stroke. The entire population includes 84% white Americans and 11% black Americans, and 59% females versus 41% males, with median age of 63 (interquartile range [IQR]: 54 to 71) years old. We utilized a topology-based K-means clustering approach for unbiased patient-patient network analyses of data from general demographics, echocardiogram (over 25,000), lab testing, and cardiac factors (cardiac). We performed hazard ratio (HR) and Kaplan-Meier analyses to identify clinically actionable variables. All confounding factors were adjusted by Cox regression models. We performed random-split and time-split training-test validation for our model. We identified 4 clinically relevant subgroups that are significantly correlated with incidence of cardiac outcomes and mortality. Among the 4 subgroups, subgroup I (n = 625) has the highest risk of de novo CTRCD (28%) with an HR of 3.05 (95% confidence interval (CI) 2.51 to 3.72). Patients in subgroup IV (n = 1,250) had the worst survival probability (HR 4.32, 95% CI 3.82 to 4.88). From longitudinal patient-patient network analyses, the patients in subgroup I had a higher percentage of de novo CTRCD and a worse mortality within 5 years after the initiation of cancer therapies compared to long-time exposure (6 to 20 years). Using clinical variable network analyses, we identified that serum levels of NT-proB-type Natriuretic Peptide (NT-proBNP) and Troponin T are significantly correlated with patient's mortality (NT-proBNP > 900 pg/mL versus NT-proBNP = 0 to 125 pg/mL, HR = 2.95, 95% CI 2.28 to 3.82, p < 0.001; Troponin T > 0.05 µg/L versus Troponin T ≤ 0.01 µg/L, HR = 2.08, 95% CI 1.83 to 2.34, p < 0.001). Study limitations include lack of independent cardio-oncology cohorts from different healthcare systems to evaluate the generalizability of the models. Meanwhile, the confounding factors, such as multiple medication usages, may influence the findings. CONCLUSIONS: In this study, we demonstrated that the patient-patient network clustering methodology is clinically intuitive, and it allows more rapid identification of cancer survivors that are at greater risk of cardiac dysfunction. We believed that this study holds great promise for identifying novel cardiac risk subgroups and clinically actionable variables for the development of precision cardio-oncology.

Short-term outcomes of transcatheter aortic valve replacement for pure native aortic regurgitation in the United States.

OBJECTIVE: We aimed to compare short-term outcomes between transcatheter aortic valve replacement (TAVR) for pure aortic regurgitation (AR) and TAVR for aortic stenosis (AS). BACKGROUND: In patients with severe pure AR for whom surgical valve replacement is infeasible, TAVR is sometimes used off-label. METHODS: Using the Nationwide Readmissions Database 2016-2017, we retrospectively identified patients without prior valve surgery who underwent endovascular TAVR. We compared in-hospital and 30-day outcomes according to the type of aortic valve disease. RESULTS: A total of 81,542 eligible patients were divided into the pure AR (n = 1,222, 1.50%), pure AS (n = 72,690, 89.1%), and AS + AR (n = 7,630, 9.36%) groups. In unadjusted analyses, the pure AR group, compared with the pure AS and AS + AR groups, showed a higher incidence of acute kidney injury (16.8% vs. 9.8% vs. 12.1%, respectively; p < .001) and need of surgical bailout (1.4% vs. 0.4% vs. 0.6%; p < .01). The pure AR group also showed higher in-hospital mortality than the pure AS group (2.4% vs. 1.4%; p = .005). After multivariable adjustment, TAVR for pure AR was significantly associated with a higher risk of acute kidney injury (odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.33-2.02; p < .001), cardiac tamponade (OR = 1.98, 95% CI = 1.00-3.92; p = .0498), and prolonged hospital stay (OR = 1.59, 95% CI = 1.29-1.95; p < .001) compared with TAVR for pure AS, whereas it was not significantly associated with in-hospital mortality (OR = 1.55, 95% CI = 0.99-2.45; p = .058) and other outcomes. CONCLUSIONS: TAVR may be a reasonable treatment option for selected patients with pure AR with regard to short-term outcomes. However, additional techniques or devices may be necessary to reduce periprocedural risk.

Impact of thoracic aortic aneurysm on outcomes of transcatheter aortic valve replacement: A nationwide cohort analysis.

BACKGROUND: The use of transcatheter aortic valve replacement (TAVR) has expanded to patient populations of varying surgical risk in light of recent clinical trials, yet its role in patients with aortic stenosis and coexisting thoracic aortic aneurysm (TAA) is not well-delineated. We aimed to evaluate whether risk factors and in-hospital outcomes vary between TAVR patients with and without an unruptured TAA. METHODS: The Nationwide Readmissions Database was queried for patients hospitalized between January 2012 and December 2017 who underwent TAVR with and without an unruptured TAA. In-hospital outcomes were compared between cohorts after adjusting for sex, comorbidities, and TAVR approach, and in a subgroup analysis that excluded those with bicuspid aortic valves. RESULTS: Among 171,011 TAVR patients, 1,677 (1%) presented with TAA. Patients with TAA were younger (median age 80 vs. 82 years, p < .001) and more likely to have bicuspid aortic valves (9.3% vs. 0.9%, p < .001). Among patients with aneurysm, 2.6% died, 2.2% developed stroke, 1% developed aortic dissection, and 1.4% experienced cardiac tamponade while hospitalized. After adjusting for age, sex, bicuspid aortic valve, and all comorbidities, TAA was associated with significantly higher risk of post-TAVR aortic dissection (OR = 2.117, 95% CI [1.304-3.435], p = .002) and cardiac tamponade (OR = 1.682, 95% CI [1.1-2.572], p = .02). CONCLUSIONS: While the overall incidence of post-TAVR complications is low, patients with an unruptured TAA should be carefully considered by the Heart Team in weighing the additional risks of aortic dissection and cardiac tamponade after TAVR with those associated with surgery.

Comparing outcomes of general anesthesia and monitored anesthesia care during transcatheter aortic valve replacement: The Cleveland Clinic Foundation experience.

BACKGROUND: Monitored anesthesia care (MAC) has become more widely used during transcatheter aortic valve replacement (TAVR) to avoid the complications of general anesthesia (GA). METHODS: We included consecutive patients who underwent transfemoral-TAVR at our institution between January 2012 and April 2017. We compared outcomes with GA versus MAC. RESULTS: Of 998 patients, MAC was used in 43.9%. MAC was associated with shorter procedural time (96.9 ± 30.9 vs. 135 ± 64.6 mins; p < .001), fluoroscopy time (20.4 ± 8.9 vs. 29 ± 18.7 mins; p < .001), lower contrast volume (45.5 ± 27 vs. 60.4 ± 43 cc; p < .001), and decreased radiation exposure (12,869 ± 8,099 vs. 20,630 ± 16,276 cGy-cm2 ; p < .001). Patients who underwent MAC had a briefer median (IQR) intensive care unit stay [23.3 (21-24) vs. 23.4 (20.8-26) hrs; p < .001], and hospital stay [2 (2, 3) vs. 3 (2-6) days; p < .001], and were more frequently discharged to home (93.4% vs. 82.9%; p < .001). MAC was associated with lower mortality at 30 days (0.5% vs. 2.9%; log-rank p = .012; adjHR 0.22, 95% CI 0.06-0.82; p = .024), but not at 1 year (11.7% vs. 14.6%; log-rank p = .157) or 3 years (36.8% vs. 38.4%; log-rank p = 0.433). There were no differences in major adverse cardiac and cerebrovascular events (MACCE) at either 30 days (4.6% vs. 9.3%; log-rank p = .14) or 1 year (21.1% vs. 21.5%; log-rank p = .653). Similar findings were seen among patients who received newer-generation SAPIEN-3 valves. CONCLUSION: Utilizing MAC and omitting intraprocedural transesophageal echocardiography during TAVR seems to be more efficient without compromising safety. Better TAVR outcomes can be achieved with newer generation valves without needing GA.

Impact of baseline conduction abnormalities on outcomes after transcatheter aortic valve replacement with SAPIEN-3.

BACKGROUND: Baseline conduction abnormalities are known risk factors for permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR). We sought to determine the impact of baseline right bundle branch block (RBBB), left bundle branch block (LBBB), left anterior hemiblock (LAHB), first-degree atrioventricular block (AVB) and atrial fibrillation/flutter (AF) on TAVR outcomes. METHODS: Consecutive patients who underwent transfemoral TAVR with SAPIEN-3 (S3) were included. We excluded patients with prior PPM, nontransfemoral access or valve-in-valve. RESULTS: Among 886 patients, baseline RBBB was seen in 15.9%, LBBB in 6.3%, LAHB in 6.2%, first-degree AVB in 26.3% and AF in 37.5%. The rate of 30-day PPM was 10.1%. Baseline RBBB (OR 4.005; 95% CI 2.386-6.723; p < .001) and first-degree AVB (OR 1.847; 95% CI 1.133-3.009; p = .014) were independent predictors of 30 day PPM. LAHB also resulted in higher PPM rates but only in unadjusted analysis (21.8% vs. 9.4%; p = .003). Baseline LBBB and AF were associated with lower left ventricular ejection fraction (LVEF) at both baseline and 1 year after TAVR. However, Δ LVEF over time were noted to be similar with baseline LBBB (1.8% vs. 1.4%; p = .809) and AF (1.1% vs. 1.7%; p = .458). Moreover, baseline AF was also associated with higher stroke/transient ischemic attack (TIA) at 1 year (4.4% vs. 1.8%; p = .019), 1-year major adverse cardiac and cerebrovascular events (MACCE) (19.5% vs. 13.3%; p = .012) and 2 year mortality (23.5% vs. 15.2%; p = .016). None of the other baseline conduction defects affected long-term mortality or MACCE. CONCLUSION: In our S3 TAVR population, baseline RBBB and first-degree AVB predicted higher PPM risk. Prior LBBB and AF were associated with lower LVEF at both baseline and 1 year. Lastly, preexisting AF was associated with higher rates of mortality, stroke/TIA, and MACCE.

Adverse clinical outcomes in patients undergoing both PCI and TAVR: Analysis from a pooled multi-center registry.

BACKGROUND: There is a paucity of data regarding the optimum timing of PCI in relation to TAVR. OBJECTIVE: We compared the major adverse cardiovascular and cerebrovascular events (MACCE) rates among patients who underwent percutaneous coronary intervention (PCI) before transcatheter aortic valve replacement (TAVR) with those who received PCI with/after TAVR. METHODS: In this multicenter study, we pooled all consecutive patients who underwent TAVR at three high volume centers. RESULTS: Among 3,982 patients who underwent TAVR, 327 (8%) patients underwent PCI within 1 year before TAVR, 38 (1%) had PCI the same day as TAVR and 15 (0.5%) had PCI within 2 months after TAVR. Overall, among patients who received both PCI and TAVR (n = 380), history of previous CABG (HR:0.501; p = .001), higher BMI at TAVR (HR:0.970; p = .038), and statin therapy after TAVR (HR:0.660, p = .037) were independently associated with lower MACCE while warfarin therapy after TAVR was associated with a higher risk of MACCE (HR:1.779, p = .017). Patients who received PCI within 1 year before TAVR had similar baseline demographics, STS scores, clinical risk factors when compared to patients receiving PCI with/after TAVR. Both groups were similar in PCI (Syntax Score, ACC/AHA lesion class) and TAVR (valve types, access) related variables. There were no significant differences in terms of MACCE (log rank p = .550), all-cause mortality (log rank p = .433), strokes (log rank p = .153), and repeat PCI (log rank p = .054) in patients who underwent PCI with/after TAVR when compared to patients who received PCI before TAVR. CONCLUSION: Among patients who underwent both PCI and TAVR, history of CABG, higher BMI, and statin therapy had lower, while those discharged on warfarin, had higher adverse event rates. Adverse events rates were similar regardless of timing of PCI.

Effect of aspirin on short-term outcomes in hospitalized patients with COVID-19.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is an ongoing viral pandemic marked by increased risk of thrombotic events. However, the role of platelets in the elevated observed thrombotic risk in COVID-19 and utility of antiplatelet agents in attenuating thrombosis is unknown. We aimed to determine if the antiplatelet effect of aspirin may mitigate risk of myocardial infarction, cerebrovascular accident, and venous thromboembolism in COVID-19. We evaluated 22,072 symptomatic patients tested for COVID-19. Propensity-matched analyses were performed to determine if treatment with aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) affected thrombotic outcomes in COVID-19. Neither aspirin nor NSAIDs affected mortality in COVID-19. Thus, aspirin does not appear to prevent thrombosis and death in COVID-19. The mechanisms of thrombosis in COVID-19, therefore, appear distinct and the role of platelets as direct mediators of SARS-CoV-2-mediated thrombosis warrants further investigation.

Cost-Effectiveness of Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis at Intermediate Risk.

BACKGROUND: In patients with severe aortic stenosis (AS) at intermediate surgical risk, treatment with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) results in similar rates of death or stroke at 2 years. Whether TAVR is cost-effective compared with SAVR for intermediate-risk patients remains uncertain. METHODS: Between 2011 and 2014, 3110 intermediate-risk AS patients were treated with TAVR or SAVR in the PARTNER 2 trial (Placement of Aortic Transcatheter Valves 2). A total of 2032 patients were randomized to receive TAVR using the SAPIEN XT valve (XT-TAVR) or SAVR in the PARTNER 2A trial, whereas the PARTNER S3i registry included an additional 1078 patients treated with TAVR using the SAPIEN 3 valve (S3-TAVR), which offers a lower delivery profile and sealing skirt designed to reduce paravalvular regurgitation compared with XT-TAVR. Procedural costs were estimated using measured resource utilization. Other in-trial costs were assessed by linkage of trial data with Medicare claims (n=2333) or by linear regression models for unlinked patients (n=682). Health utilities were estimated using the EQ-5D at baseline and 1, 12, and 24 months. Using a Markov model informed by in-trial costs, utilities, and survival data, lifetime cost-effectiveness from the perspective of the US healthcare system was estimated in terms of cost per quality-adjusted life-year gained. RESULTS: Although procedural costs were ≈$20 000 higher with TAVR than SAVR, total cost differences for the index hospitalization were only $2888 higher with XT-TAVR ( P=0.014) and were $4155 lower with S3-TAVR ( P<0.001) owing to reductions in length of stay with TAVR. Follow-up costs were significantly lower with XT-TAVR (Δ=-$9304; P<0.001) and S3-TAVR (Δ=-$11 377; P<0.001) than with SAVR. Over a lifetime horizon, TAVR was projected to lower total costs by $8000 to $10 000 and to increase quality-adjusted survival by 0.15 to 0.27 years. XT-TAVR and S3-TAVR were found to be economically dominant compared with SAVR in 84% and 97% of bootstrap replicates, respectively. CONCLUSIONS: Among intermediate-risk AS patients, TAVR is projected to be economically dominant from the perspective of the US healthcare system by providing both greater quality-adjusted life expectancy and lower long-term costs than SAVR. If long-term data demonstrate comparable late mortality with TAVR and SAVR, these findings suggest that TAVR might be the preferred treatment strategy for intermediate-risk AS patients based on both clinical and economic considerations. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01314313.