Surgeons of the Future: A Novel Screening Tool for High-School Students.

INTRODUCTION: Given a looming shortage of surgeons and currently inadequate pipelines into our specialty for under-represented groups, there is an urgent need to identify and foster interest in young individuals who may have great potential as future surgeons. We aimed to explore the utility and feasibility of a novel survey instrument to identify high-school students well suited for careers in surgery based on personality profiling and grit. METHODS: An electronic screening tool was developed, combining components of the Myers-Briggs personality profile, the Big-Five Inventory 10, and the grit scale. This brief questionnaire was electronically distributed to surgeons and students across two academic institutions and three high schools (one private and two public). Wilcoxon rank-sum test and Chi-squared/Fisher's exact test were performed to evaluate variations between groups. RESULTS: Surgeons (n = 96) displayed mean Grit score of 4.03 (range: 3.08-4.92; standard deviation: 0.43), while high-schoolers' (n = 61) mean score was 3.38 (range: 2.08-4.58; standard deviation: 0.62) (P < 0.0001). Surgeons showed Myers-Brigg Type Indicator trait-dominance toward extroversion, intuition, thinking, and judging, while students displayed greater breadth of traits. Students were much less likely to show dominance in introversion versus extroversion (P < 0.0001) as well as perceiving versus judging (P < 0.0001). Big-Five Inventory 10 traits of neuroticism and conscientiousness were more prevalent among surgeons (P < 0.0001 for both). CONCLUSIONS: Importantly, there exists a subgroup of high-school students with personality and grit similar to those of surgeons. Moreover, we have demonstrated the feasibility of using this novel screening tool for future studies aimed to create pipelines for early exposure opportunities and mentorship.

An Analysis of Waitlist Inactivity Among Patients With Ventricular Assist Devices.

BACKGROUND: Ventricular assist devices (VADs) are commonly used mechanical circulatory support for bridge to transplant therapy in end-stage heart failure; however, it is not understood how VADs influence incidence of waitlist inactive status. We sought to characterize and compare waitlist inactivity among patients with and without VADs. METHODS: Using the Organ Procurement and Transplantation Network database, we investigated the VAD's impact on incidence and length of inactive periods for heart transplant candidates from 2005 through 2018. We compared median length of inactivity between patients with and without VADs and investigated inactivity risk with time-to-event regression models. RESULTS: Among 46,441 heart transplant candidates, 32% (n = 14,636) had a VAD. Thirty-eight percent (n = 17,873) of all patients experienced inactivity, of which 42% (7538/17,873) had a VAD. Median inactivity length was 31 d for patients without VADs and 62 d for VAD patients (P < 0.0005). Multivariable analysis showed no significant difference in risk of inactivity for deteriorating conditions between patients with and without VADs after controlling for demographic and baseline clinical variables. A larger proportion of patients without VADs were inactive for deteriorating conditions than VAD patients (54%, n = 8242/15,221 versus 32%, n = 3583/11,086, P < 0.001). Ten percent (1155/11,086) of VAD patients' inactive periods were for VAD-related complications. CONCLUSIONS: Although VAD patients were inactive longer and had an overall increased risk of any-cause inactivity, their risk of inactivity for deteriorating condition was not significantly different from patients without VADs. Furthermore, VAD patients had a smaller proportion of inactivity periods due to deteriorating conditions. Thus, VADs are protective from morbidity for waitlist patients.

High rates of de novo malignancy compromise post-heart transplantation survival.

BACKGROUND: Transplant patients are known to have increased risk of developing de novo malignancies (DNMs). As post-transplant survival increases, DNM represents an obstacle to further improving survival. We sought to examine the incidence, types, and risk factors for post-transplant DNM. METHODS: We studied adult heart transplant recipients from the Organ Procurement and Transplantation Network database (1987-2018). Kaplan-Meier survival analysis was performed to determine annual probabilities of developing DNM, excluding squamous and basal cell carcinoma. Rates were compared to the general population in the Surveillance, Epidemiology, and End Results database. Cox proportional hazards regression was performed to calculate hazard ratios for risk factors of DNM development, all-cause, and cancer-specific mortality. RESULTS: Over median follow-up of 6.9 years, 18% of the 49,361 patients developed DNM, which correlated with an incidence rate 3.8 times that of the general population. The most common malignancies were lung, post-transplant lymphoproliferative disorder, and prostate. Risk was most increased for female genital, tongue/throat, and renal cancers. Male gender, older age, smoking history, and impaired renal function were risk factors for developing DNM, whereas the use of MMF for immunosuppression was protective. Cigarette use, increasing age, the use of ATG for induction and calcineurin inhibitors for maintenance were risk factors for cancer-specific mortality. The development of a DNM increased the risk of death by 40% (p < .001). CONCLUSIONS: Heart transplant patients are at increased risk of malignancy, particularly rare cancers, which significantly increases their risk of death. Strict cancer surveillance and attention to immunosuppression are critical for prolonging post-transplant survival.

Persistent Racial and Sex Disparities in Outcomes After Coronary Artery Bypass Surgery: A Retrospective Clinical Registry Review in the Drug-eluting Stent Era.

OBJECTIVE: The purpose of this study was to assess the temporal trends in 30-day mortality by race group for patients undergoing coronary artery bypass grafting (CABG) between 2011 and 2018 and to investigate the effect of race and sex on postoperative outcomes after CABG. SUMMARY BACKGROUND DATA: Cardiovascular diseases remain a leading cause of death in the United States with studies demonstrating increased morbidity and mortality for black and female patients undergoing surgery. In the post drug-eluting stent era, studies of racial disparities CABG are outdated. METHODS: We performed a retrospective analysis of the Society for Thoracic Surgeons database for patients undergoing CABG between 2011 and 2018. Primary outcome was 30-day mortality. Secondary outcomes included postoperative length of stay, surgical site infection, sepsis, pneumonia, stroke, reoperation, reintervention, early extubation, and readmission. RESULTS: The study population was comprised of 1,042,506 patients who underwent isolated CABG between 2011 and 2018. Among all races, Black patients had higher rates of preoperative comorbidities. Compared with White patients, Black patients had higher overall mortality (2.76% vs 2.19%, P < 0.001). On univariable regression, Black patients had higher rates of death, infection, pneumonia, and postoperative stroke compared to White patients. On multivariable regression, Black patients had higher odds of 30-day mortality compared to white patients [odds ratio (OR) = 1.11, 95% confidence interval (CI) 1.05-1.18]. Similarly, female patients had higher odds of death compared to males (OR = 1.26, 95% CI 1.21-1.30). CONCLUSIONS: In the modern era, racial and sex disparities in mortality and postoperative morbidity after coronary bypass surgery persist with Black patients and female patients consistently experiencing worse outcomes than White male patients. Although there may be unknown or underappreciated biological mechanisms at play, future research should focus on socioeconomic, cultural, and multilevel factors.

Ventricular assist devices and middle age reduce heart transplantation rates for waitlist candidates.

BACKGROUND: Ventricular assist devices (VADs) are commonly employed as a bridge to transplantation for heart failure. The full effects of VADs on transplantation rates are not fully understood. We sought to compare transplantation rates stratified by age and VAD status. METHODS: Using the Organ Procurement and Transplantation Network (OPTN) database, we investigated the impact of age and VAD status on heart allocation rates among all transplant-eligible patients from January 2005 to September 2018. Patients were grouped based on the presence (+) or absence (-) of a VAD as well as age (<45, 45-65, and >65 years). Demographics were compared with a multivariate competing risk analysis that yielded risk-adjusted subdistribution hazard ratios (SHR). RESULTS: Among the 50 602 total waitlist candidates, 18 271 patients with a VAD had higher rates of diabetes and cerebrovascular disease at waitlist entry. Multivariate analysis found statistically significant lower rates of transplantation for all (+)VAD groups compared with age-matched (-)VAD counterparts, with the 45- to 65-year-old (+)VAD group having the lowest transplantation rate (SHR = 0.62; P < .0005). Among (-)VAD patients, transplantation rates increased with increase in age. CONCLUSIONS: There is a statistically significant reduced rate of transplantation for patients with a VAD compared with those without a VAD, with the lowest rate among those of ages 45 to 65 years with a VAD. The increasing prevalence of this demographic and the deprioritization of VADs in the new heart allocation criteria have the potential to further exacerbate this difference.

Etiology-dependent impairment of relaxation kinetics in right ventricular end-stage failing human myocardium.

BACKGROUND: In patients with end-stage heart failure, the primary etiology often originates in the left ventricle, and eventually the contractile function of the right ventricle (RV) also becomes compromised. RV tissue-level deficits in contractile force and/or kinetics need quantification to understand involvement in ischemic and non-ischemic failing human myocardium. METHODS AND RESULTS: The human population suffering from heart failure is diverse, requiring many subjects to be studied in order to perform an adequately powered statistical analysis. From 2009-present we assessed live tissue-level contractile force and kinetics in isolated myocardial RV trabeculae from 44 non-failing and 41 failing human hearts. At 1 Hz stimulation rate (in vivo resting state) the developed active force was not different in non-failing compared to failing ischemic nor non-ischemic failing trabeculae. In sharp contrast, the kinetics of relaxation were significantly impacted by disease, with 50% relaxation time being significantly shorter in non-failing vs. non-ischemic failing, while the latter was still significantly shorter than ischemic failing. Gender did not significantly impact kinetics. Length-dependent activation was not impacted. Although baseline force was not impacted, contractile reserve was critically blunted. The force-frequency relation was positive in non-failing myocardium, but negative in both ischemic and non-ischemic myocardium, while the ß-adrenergic response to isoproterenol was depressed in both pathologies. CONCLUSIONS: Force development at resting heart rate is not impacted by cardiac pathology, but kinetics are impaired and the magnitude of the impairment depends on the underlying etiology. Focusing on restoration of myocardial kinetics will likely have greater therapeutic potential than targeting force of contraction.

SCN5A variant that blocks fibroblast growth factor homologous factor regulation causes human arrhythmia.

Nav channels are essential for metazoan membrane depolarization, and Nav channel dysfunction is directly linked with epilepsy, ataxia, pain, arrhythmia, myotonia, and irritable bowel syndrome. Human Nav channelopathies are primarily caused by variants that directly affect Nav channel permeability or gating. However, a new class of human Nav channelopathies has emerged based on channel variants that alter regulation by intracellular signaling or cytoskeletal proteins. Fibroblast growth factor homologous factors (FHFs) are a family of intracellular signaling proteins linked with Nav channel regulation in neurons and myocytes. However, to date, there is surprisingly little evidence linking Nav channel gene variants with FHFs and human disease. Here, we provide, to our knowledge, the first evidence that mutations in SCN5A (encodes primary cardiac Nav channel Nav1.5) that alter FHF binding result in human cardiovascular disease. We describe a five*generation kindred with a history of atrial and ventricular arrhythmias, cardiac arrest, and sudden cardiac death. Affected family members harbor a novel SCN5A variant resulting in p.H1849R. p.H1849R is localized in the central binding core on Nav1.5 for FHFs. Consistent with these data, Nav1.5 p.H1849R affected interaction with FHFs. Further, electrophysiological analysis identified Nav1.5 p.H1849R as a gain-of-function for INa by altering steady-state inactivation and slowing the rate of Nav1.5 inactivation. In line with these data and consistent with human cardiac phenotypes, myocytes expressing Nav1.5 p.H1849R displayed prolonged action potential duration and arrhythmogenic afterdepolarizations. Together, these findings identify a previously unexplored mechanism for human Nav channelopathy based on altered Nav1.5 association with FHF proteins.

Racial disparities in outcomes of adult heart transplantation.

BACKGROUND: This study evaluated whether minority orthotopic heart transplant (OHT) recipients tend to be transplanted at worse performing centers. METHODS AND RESULTS: OHT recipients between 2000 and 2010 were identified in the United Network for Organ Sharing database and stratified by race. Center performance was evaluated using observed-to-expected mortality ratios that were calculated using validated indexes for recipient and donor risk in OHT. The primary outcome was 1-year post-OHT mortality. A total of 102 centers performed OHT in 18 085 patients. Blacks had higher unadjusted 1-year mortality, which was confirmed after risk adjustment. Blacks had increased risk-adjusted mortality at poor performing centers (observed-to-expected mortality ratio, >1.2; odds ratio, 1.37 [95% confidence interval, 1.12-1.69]; P=0.002) and a strong trend toward increased mortality at excellent performing centers (observed-to-expected mortality ratio, <0.8; odds ratio, 1.42 [95% confidence interval, 0.99-2.02]; P=0.06). A higher proportion of blacks were treated at centers with higher-than-expected mortality (56.4% versus 47.1% whites versus 48.1% Hispanics; P<0.001), a finding that persisted after adjusting for insurance type and highest education level. In addition, there was a positive correlation between the percentage of blacks and observed-to-expected mortality ratios at the center level (r=0.32; P=0.001). In multivariable analysis incorporating immunologic and socioeconomic variables, there was no clear dominant source for the disparities in outcomes of OHT between races. CONCLUSIONS: Blacks have a propensity to be transplanted at worse performing centers; however, center effect alone does not explain the mortality difference between ethnicities. Although referral of minorities to better performing centers would improve absolute survival, it would not likely eliminate the racial disparities that exist in OHT outcomes.

Insights into length-dependent regulation of cardiac cross-bridge cycling kinetics in human myocardium.

Cross-bridge cycling kinetics play an essential role in the heart's ability to contract and relax. The rate of tension redevelopment (ktr) slows down as a muscle length is increased in intact human myocardium. We set out to determine the effect of rapid length step changes and protein kinase A (PKA) and protein kinase C-ßII (PKC-ßII) inhibitors on the ktr in ultra-thin non-failing and failing human right ventricular trabeculae. After stabilizing the muscle either at L90 (90% of optimal length) or at Lopt (optimal length), we rapidly changed the length to either Lopt or L90 and measured ktr. We report that length-dependent changes in ktr occur very rapidly (in the order of seconds or faster) in both non-failing and failing muscles and that the length at which a muscle had been stabilized prior to the length change does not significantly affect ktr. In addition, at L90 and at Lopt, PKA and PKC-ßII inhibitors did not significantly change ktr. Our results reveal that length-dependent regulation of cross-bridge cycling kinetics predominantly occurs rapidly and involves the intrinsic properties of the myofilament rather than post-translational modifications that are known to occur in the cardiac muscle as a result of a change in muscle/sarcomere length.

Atrial fibrillation driven by micro-anatomic intramural re-entry revealed by simultaneous sub-epicardial and sub-endocardial optical mapping in explanted human hearts.

AIMS: The complex architecture of the human atria may create physical substrates for sustained re-entry to drive atrial fibrillation (AF). The existence of sustained, anatomically defined AF drivers in humans has been challenged partly due to the lack of simultaneous endocardial-epicardial (Endo-Epi) mapping coupled with high-resolution 3D structural imaging. METHODS AND RESULTS: Coronary-perfused human right atria from explanted diseased hearts (n = 8, 43-72 years old) were optically mapped simultaneously by three high-resolution CMOS cameras (two aligned Endo-Epi views (330 µm2 resolution) and one panoramic view). 3D gadolinium-enhanced magnetic resonance imaging (GE-MRI, 80 µm3 resolution) revealed the atrial wall structure varied in thickness (1.0 ± 0.7-6.8 ± 2.4 mm), transmural fiber angle differences, and interstitial fibrosis causing transmural activation delay from 23 ± 11 to 43 ± 22 ms at increased pacing rates. Sustained AF (>90 min) was induced by burst pacing during pinacidil (30-100 µM) perfusion. Dual-sided sub-Endo-sub-Epi optical mapping revealed that AF was driven by spatially and temporally stable intramural re-entry with 107 ± 50 ms cycle length and transmural activation delay of 67 ± 31 ms. Intramural re-entrant drivers were captured primarily by sub-Endo mapping, while sub-Epi mapping visualized re-entry or 'breakthrough' patterns. Re-entrant drivers were anchored on 3D micro-anatomic tracks (15.4 ± 2.2 × 6.0 ± 2.3 mm2, 2.9 ± 0.9 mm depth) formed by atrial musculature characterized by increased transmural fiber angle differences and interstitial fibrosis. Targeted radiofrequency ablation of the tracks verified these re-entries as drivers of AF. CONCLUSIONS: Integrated 3D structural-functional mapping of diseased human right atria ex vivo revealed that the complex atrial microstructure caused significant differences between Endo vs. Epi activation during pacing and sustained AF driven by intramural re-entry anchored to fibrosis-insulated atrial bundles.

Induction Therapy for Lung Transplantation in COPD: Analysis of the UNOS Registry.

Although studies demonstrate that induction therapy improves outcomes after lung transplantation, its influence on survival in patients with chronic obstructive pulmonary disease (COPD) is not clear. The United Network for Organ Sharing database was queried to obtain data regarding adult patients with COPD receiving lung transplant between May 2005 and June 2014. Therapies evaluated include anti-thymocyte globulin, anti-lymphocyte globulin, thymoglobulin, basiliximab, and alemtuzumab. Data were categorized based on receiving induction (INDUCED) and no induction (NONE). Kaplan-Meier plots, Cox proportional hazards models of patient survival, and competing-risks regression models for secondary endpoints were utilized. A total of 3,405 patients who underwent lung transplantation for COPD were enrolled with 1,761 (52%) receiving induction therapy. Of INDUCED, 1,146 (65%) received basiliximab, 380 (22%) received alemtuzumab, and 235 (13%) received a polyclonal preparation. The hazard ratio for INDUCED vs. NONE was 0.793 (95% CI = 0.693, 0.909; p = 0.001) in the fully adjusted Cox model. A multivariable competing-risks model also found a protective influence of induction therapy with respect to delayed onset of bronchiolitis obliterans syndrome after transplantation (SHR = 0.801; 95% CI = 0.694, 0.925; p = 0.003). In a cohort of recently transplanted patients with COPD, there appears to be a benefit from contemporary induction agents with no concurrent increase in the risk of death due to infection.

The Frank-Starling mechanism involves deceleration of cross-bridge kinetics and is preserved in failing human right ventricular myocardium.

Cross-bridge cycling rate is an important determinant of cardiac output, and its alteration can potentially contribute to reduced output in heart failure patients. Additionally, animal studies suggest that this rate can be regulated by muscle length. The purpose of this study was to investigate cross-bridge cycling rate and its regulation by muscle length under near-physiological conditions in intact right ventricular muscles of nonfailing and failing human hearts. We acquired freshly explanted nonfailing (n = 9) and failing (n = 10) human hearts. All experiments were performed on intact right ventricular cardiac trabeculae (n = 40) at physiological temperature and near the normal heart rate range. The failing myocardium showed the typical heart failure phenotype: a negative force-frequency relationship and ß-adrenergic desensitization (P < 0.05), indicating the expected pathological myocardium in the right ventricles. We found that there exists a length-dependent regulation of cross-bridge cycling kinetics in human myocardium. Decreasing muscle length accelerated the rate of cross-bridge reattachment (ktr) in both nonfailing and failing myocardium (P < 0.05) equally; there were no major differences between nonfailing and failing myocardium at each respective length (P > 0.05), indicating that this regulatory mechanism is preserved in heart failure. Length-dependent assessment of twitch kinetics mirrored these findings; normalized dF/dt slowed down with increasing length of the muscle and was virtually identical in diseased tissue. This study shows for the first time that muscle length regulates cross-bridge kinetics in human myocardium under near-physiological conditions and that those kinetics are preserved in the right ventricular tissues of heart failure patients.

Impact of induction immunosuppression on survival in heart transplant recipients: a contemporary analysis of agents.

INTRODUCTION: The impact of induction immunosuppression on long-term survival in heart transplant recipients is unclear. Over the past three decades, practices have varied as induction agents have changed and experiences grew. We sought to evaluate the effect of contemporary induction immunosuppression agents in heart transplant recipients with the primary endpoint of survival, utilizing national registry data. METHODS: We queried the United Network for Organ Sharing (UNOS) data registry for all heart transplants from 1987 to 2012. We restricted our analysis to adult (≥18 yr) recipients performed from 2001-2011 (to allow for the potential for a minimum of 12 months post-transplant follow-up) who received either: no antibody based induction (NONE) or the contemporary agents (INDUCED) of either: basiliximab/daclizumab (IL-2Rab), alemtuzumab, or ATG/ALG/thymoglobulin. Kaplan-Meier estimates of the survival function as well as Cox proportional hazards models were utilized. RESULTS: Of the 17 857 heart transplants that met the inclusion criteria, there were 4635 (26%) reported deaths during the follow-up period. There were 8216 (46%) patients who were INDUCED. Of the INDUCED agents, 55% were IL-2Rab, 4% alemtuzumab, and 40% ALG/ATG/thymoglobulin. Donor and recipient characteristics were evaluated. Overall, being INDUCED did not significantly affect survival in univariable (p = 0.522) and multivariable (p = 0.130) Cox models as well as a propensity score adjusted model (p = 0.733). Among those induced, ATG/ALG/thymoglobulin appeared to have superior survival as compared with IL-2Rab (log-rank p = 0.007, univariable hazard ratio [HR] = 0.886; 95% CI: 0.811-0.968; p = 0.522). However, in a multivariable Cox model that adjusted for recipient age, VAD, BMI, steroid use, CMV match, and ischemic time, the hazard ratio for ALG/ATG/thymoglobulin vs. IL-2Rab was no longer statistically significant (HR = 0.948; 95% CI: 0.850-1.058; p = 0.341). CONCLUSION: In a contemporary analysis of heart transplant recipients, an overall analysis of induction agents does not appear to impact survival, as compared to no induction immunosuppression. While ALG/ATG/thymoglobulin appeared to have a beneficial effect on survival compared to IL-2Rab in the univariable model, this difference was no longer statistically significant once we adjusted for clinically relevant covariates.

To induce or not to induce: a 21st century evaluation of lung transplant immunosuppression's effect on survival.

INTRODUCTION: The impact of induction immunosuppression on long-term survival in lung transplant recipients remains unclear. We sought to evaluate the effect of contemporary induction immunosuppression agents in lung transplant recipients' survival, utilizing national registry data. METHODS: We queried the United Network for Organ Sharing registry from 2001 to 2012 for adult, deceased donor lung transplants who received no antibody-based induction (NONE) or the contemporary agents of basiliximab, alemtuzumab, thymoglobulin, antilymphocyte globulin, or antithymocyte globulin (INDUCED). Kaplan-Meier estimates of the survival and Cox proportional hazards models assessed differences in overall survival between the INDUCED and NONE groups; logistic regression models assessed differences in survival and rejection (TR1Y). RESULTS: There were 23 951 lung transplants performed with 12 858 meeting the inclusion criteria; 5713 (44%) were INDUCED. Of INDUCED agents, 62% were basiliximab and 14% alemtuzumab. Being INDUCED significantly increased overall survival (p < 0.0001). Median INDUCED survival was 71.3 months (confidence interval [CI]: 65.7-75.5) as compared with 63.2 months (CI: 60.1-65.9). Of INDUCED, both basiliximab and alemtuzumab had higher median survival times at 75.1 months (CI: 68.6-81.3) and 75.5 months (CI: 63.5-∞), respectively. There was less TR1Y in INDUCED patients (37%), as compared to NONE (42%; p < 0.0001). CONCLUSION: In a contemporary analysis of lung transplant recipients, induction immunosuppression has a significantly positive effect on survival.

Simultaneous procedures during left ventricular assist device implantation: is less always more?

In up to 50% of patients undergoing continuous flow, axial pump, left-ventricular and assist device (LVAD) placement, concomitant procedures are performed. The underlying lesions have a broad spectrum of severity, complexity, and impact on clinical outcomes. This review describes the concomitant lesions often encountered with LVAD implantation and clinical relevance of their repair.

Racial disparities among patients on venovenous extracorporeal membrane oxygenation in the pre-Coronavirus Disease 2019 and Coronavirus Disease 2019 eras: A retrospective registry review.

Objectives: Although many studies have addressed such disparities caused by COVID-19, to our knowledge, no study has focused on the association of race on outcomes for patients with COVID-19 requiring venovenous extracorporeal membrane oxygenation support. The goal of this study was to assess association of race on death and duration on venovenous extracorporeal membrane oxygenation in both the pre-COVID-19 and COVID-19 eras. Methods: We retrospectively reviewed the Extracorporeal Life Support Organization registry and included adults (≥18 years) who required venovenous extracorporeal membrane oxygenation between January 2019 and April 2021. We performed descriptive statistics and multivariable logistic regression. Our primary outcomes were death and extracorporeal membrane oxygenation duration. Results: A total of 7477 patients were included after excluding 340 patients (4.3%) who were missing race data. In the COVID-19 era, 1474 of 2777 COVID-19-positive patients (53.1%) died. Our regression model suggested somewhat of a protective effect on death for Black and multiple race patients. Additionally, a diagnosis of COVID-19 and patients in the COVID-19 era in general, irrespective of COVID-19 diagnosis, had higher odds of death. Hispanic patients had the longest average venovenous extracorporeal membrane oxygenation run times. Conclusions: Our study using data from the international Extracorporeal Life Support Organization Registry provides updated data on patients supported with venovenous extracorporeal membrane oxygenation in the pre-COVID-19 and COVID-19 eras between 2019 and 2021 with a focus on race. Patients in the COVID-19 era group also had higher mortality compared with those in the pre-COVID-19 era even after being adjusted for COVID-19 diagnosis. Black and multiple races appeared somewhat protective in terms of death. Hispanic race was associated with longer venovenous extracorporeal membrane oxygenation duration.

The rates of Ca2+ dissociation and cross-bridge detachment from ventricular myofibrils as reported by a fluorescent cardiac troponin C.

The rate-limiting step of cardiac muscle relaxation has been proposed to reside in the myofilament. Both the rates of cross-bridge detachment and Ca(2+) dissociation from troponin C (TnC) have been hypothesized to rate-limit myofilament inactivation. In this study we used a fluorescent TnC to measure both the rate of Ca(2+) dissociation from TnC and the rate of cross-bridge detachment from several different species of ventricular myofibrils. The fluorescently labeled TnC was sensitive to both Ca(2+) dissociation and cross-bridge detachment at low Ca(2+) (presence of EGTA), allowing for a direct comparison between the two proposed rates of myofilament inactivation. Unlike Ca(2+) dissociation from TnC, cross-bridge detachment varied in myofibrils from different species and was rate-limited by ADP release. At subphysiological temperatures (<20 °C), the rate of Ca(2+) dissociation from TnC was faster than the rate of cross-bridge detachment in the presence of ADP. These results support the hypothesis that cross-bridge detachment rate-limits relaxation. However, Ca(2+) dissociation from TnC was not as temperature-sensitive as cross-bridge detachment. At a near physiological temperature (35 °C) and ADP, the rate of cross-bridge detachment may actually be faster than the rate of Ca(2+) dissociation. This provides evidence that there may not be a simple, single rate-limiting step of myofilament inactivation.

Ankyrin-B protein in heart failure: identification of a new component of metazoan cardioprotection.

Ankyrins (ankyrin-R, -B, and -G) are adapter proteins linked with defects in metazoan physiology. Ankyrin-B (encoded by ANK2) loss-of-function mutations are directly associated with human cardiovascular phenotypes including sinus node disease, atrial fibrillation, ventricular tachycardia, and sudden cardiac death. Despite the link between ankyrin-B dysfunction and monogenic disease, there are no data linking ankyrin-B regulation with common forms of human heart failure. Here, we report that ankyrin-B levels are altered in both ischemic and non-ischemic human heart failure. Mechanistically, we demonstrate that cardiac ankyrin-B levels are tightly regulated downstream of reactive oxygen species, intracellular calcium, and the calcium-dependent protease calpain, all hallmarks of human myocardial injury and heart failure. Surprisingly, ß(II)-spectrin, previously thought to mediate ankyrin-dependent modulation in the nervous system and heart, is not coordinately regulated with ankyrin-B or its downstream partners. Finally, our data implicate ankyrin-B expression as required for vertebrate myocardial protection as hearts deficient in ankyrin-B show increased cardiac damage and impaired function relative to wild-type mouse hearts following ischemia reperfusion. In summary, our findings provide the data of ankyrin-B regulation in human heart failure, provide insight into candidate pathways for ankyrin-B regulation in acquired human cardiovascular disease, and surprisingly, implicate ankyrin-B as a molecular component for cardioprotection following ischemia.

Risk score for predicting long-term mortality after coronary artery bypass graft surgery.

BACKGROUND: No simplified bedside risk scores have been created to predict long-term mortality after coronary artery bypass graft surgery. METHODS AND RESULTS: The New York State Cardiac Surgery Reporting System was used to identify 8597 patients who underwent isolated coronary artery bypass graft surgery in July through December 2000. The National Death Index was used to ascertain patients' vital statuses through December 31, 2007. A Cox proportional hazards model was fit to predict death after CABG surgery using preprocedural risk factors. Then, points were assigned to significant predictors of death on the basis of the values of their regression coefficients. For each possible point total, the predicted risks of death at years 1, 3, 5, and 7 were calculated. It was found that the 7-year mortality rate was 24.2 in the study population. Significant predictors of death included age, body mass index, ejection fraction, unstable hemodynamic state or shock, left main coronary artery disease, cerebrovascular disease, peripheral arterial disease, congestive heart failure, malignant ventricular arrhythmia, chronic obstructive pulmonary disease, diabetes mellitus, renal failure, and history of open heart surgery. The points assigned to these risk factors ranged from 1 to 7; possible point totals for each patient ranged from 0 to 28. The observed and predicted risks of death at years 1, 3, 5, and 7 across patient groups stratified by point totals were highly correlated. CONCLUSION: The simplified risk score accurately predicted the risk of mortality after coronary artery bypass graft surgery and can be used for informed consent and as an aid in determining treatment choice.