The UTHealth Houston Adult Cardiovascular Genomics Certificate Program: Efficacy and Impact on Healthcare Professionals.

Background: The demand for genetic services has outpaced the availability of resources, challenging clinicians untrained in genetic integration into clinical decision-making. The UTHealth Adult Cardiovascular Genomics Certificate (CGC) program trains non-genetic healthcare professionals to recognize, assess, and refer patients with heritable cardiovascular diseases. This asynchronous online course includes 24 modules in three tiers of increasing complexity, using realistic clinical scenarios, interactive dialogues, quizzes, and tests to reinforce learning. We hypothesized that the CGC will increase genomic competencies in this underserved audience and encourage applying genomic concepts in clinical practice. Methods: Required course evaluations include pre- and post-assessments, knowledge checks in each module, and surveys for module-specific feedback. After 6 months, longitudinal feedback surveys gathered data on the long-term impact of the course on clinical practice and conducted focused interviews with learners. Results: The CGC was accredited in September 2022. Principal learners were nurses (24%), nurse practitioners (21%), physicians (16%), and physician assistants. Scores of 283 learners in paired pre- and post-assessments increased specific skills related to recognizing heritable diseases, understanding inheritance patterns, and interpreting genetic tests. Interviews highlighted the CGC's modular structure and linked resources as key strengths. Learners endorsed confidence to use genetic information in clinical practice, such as discussing genetic concepts and risks with patients and referring patients for genetic testing. Learners were highly likely to recommend the CGC to colleagues, citing its role in enhancing heritable disease awareness. Conclusions: The CGC program effectively empowers non-genetic clinicians to master genomic competencies, fostering collaboration to prevent deaths from heritable cardiovascular diseases, and potentially transforming healthcare education and clinical practice.

The BMAL1/HIF2A heterodimer modulates circadian variations of myocardial injury.

Acute myocardial infarction stands as a prominent cause of morbidity and mortality worldwide1-6. Clinical studies have demonstrated that the severity of cardiac injury following myocardial infarction exhibits a circadian pattern, with larger infarct sizes and poorer outcomes in patients experiencing morning onset myocardial infarctions7-14. However, the molecular mechanisms that govern circadian variations of myocardial injury remain unclear. Here, we show that BMAL114-20, a core circadian transcription factor, orchestrates diurnal variability in myocardial injury. Unexpectedly, BMAL1 modulates circadian-dependent cardiac injury by forming a transcriptionally active heterodimer with a non-canonical partner, hypoxia-inducible factor 2 alpha (HIF2A)6,21-23, in a diurnal manner. Substantiating this finding, we determined the cryo-EM structure of the BMAL1/HIF2A/DNA complex, revealing a previously unknown capacity for structural rearrangement within BMAL1, which enables the crosstalk between circadian rhythms and hypoxia signaling. Furthermore, we identified amphiregulin (AREG) as a rhythmic transcriptional target of the BMAL1/HIF2A heterodimer, critical for regulating circadian variations of myocardial injury. Finally, pharmacologically targeting the BMAL1/HIF2A-AREG pathway provides effective cardioprotection, with maximum efficacy when aligned with the pathway's circadian trough. Our findings not only uncover a novel mechanism governing the circadian variations of myocardial injury but also pave the way for innovative circadian-based treatment strategies, potentially shifting current treatment paradigms for myocardial infarction.

Perioperative Quality Initiative (POQI) consensus statement on perioperative assessment of right ventricular function.

BACKGROUND: The right ventricle (RV) plays a central  role in the maintenance of effective cardiac pump function. Despite overwhelming evidence that perioperative RV dysfunction (RVD) and failure (RVF) are associated with poor clinical outcomes, there are very few published recommendations or guidelines for comprehensive, evidence-based RV assessment on the risk of developing either during the perioperative period. MAIN TEXT: To address this gap, the Perioperative Quality Initiative-IX (POQI-IX) investigators group, comprised of clinical experts in anesthesiology, cardiovascular surgery, internal medicine, critical care medicine, and advanced practice nursing, has developed a consensus statement based on current literature, published society recommendations, and the clinical expertise of the group. Herein, the group provides recommendations and evidence-based tools related to perioperative RV assessment, functional screening, staging, and the clinical implications of each. These assessment tools are based on comprehensive patient evaluation consisting of physical examination, biomarker data, imaging, and hemodynamic assessment. CONCLUSION: This review presents a comprehensive tool for assessing perioperative RV function. We hope that this simple, intuitive tool can be applied to all phases of perioperative care and thereby improve patient outcomes.

Targeting myocardial equilibrative nucleoside transporter ENT1 provides cardioprotection by enhancing myeloid Adora2b signaling.

Previous studies implicate extracellular adenosine signaling in attenuating myocardial ischemia and reperfusion injury (IRI). This extracellular adenosine signaling is terminated by its uptake into cells by equilibrative nucleoside transporters (ENTs). Thus, we hypothesized that targeting ENTs would function to increase cardiac adenosine signaling and concomitant cardioprotection against IRI. Mice were exposed to myocardial ischemia and reperfusion injury. Myocardial injury was attenuated in mice treated with the nonspecific ENT inhibitor dipyridamole. A comparison of mice with global Ent1 or Ent2 deletion showed cardioprotection only in Ent1-/- mice. Moreover, studies with tissue-specific Ent deletion revealed that mice with myocyte-specific Ent1 deletion (Ent1loxP/loxP Myosin Cre+ mice) experienced smaller infarct sizes. Measurements of cardiac adenosine levels demonstrated that postischemic elevations of adenosine persisted during reperfusion after targeting ENTs. Finally, studies in mice with global or myeloid-specific deletion of the Adora2b adenosine receptor (Adora2bloxP/loxP LysM Cre+ mice) implied that Adora2b signaling on myeloid-inflammatory cells in cardioprotection provided by ENT inhibition. These studies reveal a previously unrecognized role for myocyte-specific ENT1 in cardioprotection by enhancing myeloid-dependent Adora2b signaling during reperfusion. Extension of these findings implicates adenosine transporter inhibitors in cardioprotection against ischemia and reperfusion injury.

Does the Type of Chronic Heart Failure Impact In-Hospital Outcomes for Aortic Valve Replacement Procedures?

BACKGROUND: This study assessed in-hospital outcomes of patients with chronic systolic, diastolic, or mixed heart failure (HF) undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). METHODS: The Nationwide Inpatient Sample database was used to identify patients with aortic stenosis and chronic HF who underwent TAVR or SAVR between 2012 and 2015. Propensity score matching and multivariate logistic regression were used to determine outcome risk. RESULTS: A cohort of 9,879 patients with systolic (27.2%), diastolic (52.2%), and mixed (20.6%) chronic HF were included. No statistically significant differences in hospital mortality were noted. Overall, patients with diastolic HF had the shortest hospital stays and lowest costs. Compared with patients with diastolic HF, the risk of acute myocardial infarction (TAVR odds ratio [OR], 1.95; 95% CI, 1.20-3.19; P = .008; SAVR OR, 1.38; 95% CI, 0.98-1.95; P = .067) and cardiogenic shock (TAVR OR, 2.15; 95% CI, 1.43-3.23; P < .001; SAVR OR, 1.89; 95% CI, 1.42-2.53; P ≤ .001) was higher in patients with systolic HF, whereas the risk of permanent pacemaker implantation (TAVR OR, 0.58; 95% CI, 0.45-0.76; P < .001; SAVR OR, 0.58; 95% CI, 0.40-0.84; P = .004) was lower following aortic valve procedures. In TAVR, the risk of acute deep vein thrombosis and kidney injury was higher, although not statistically significant, in patients with systolic HF than in those with diastolic HF. CONCLUSION: These outcomes suggest that chronic HF types do not incur statistically significant hospital mortality risk in patients undergoing TAVR or SAVR.

Interplay of hypoxia-inducible factors and oxygen therapy in cardiovascular medicine.

Mammals have evolved to adapt to differences in oxygen availability. Although systemic oxygen homeostasis relies on respiratory and circulatory responses, cellular adaptation to hypoxia involves the transcription factor hypoxia-inducible factor (HIF). Given that many cardiovascular diseases involve some degree of systemic or local tissue hypoxia, oxygen therapy has been used liberally over many decades for the treatment of cardiovascular disorders. However, preclinical research has revealed the detrimental effects of excessive use of oxygen therapy, including the generation of toxic oxygen radicals or attenuation of endogenous protection by HIFs. In addition, investigators in clinical trials conducted in the past decade have questioned the excessive use of oxygen therapy and have identified specific cardiovascular diseases in which a more conservative approach to oxygen therapy could be beneficial compared with a more liberal approach. In this Review, we provide numerous perspectives on systemic and molecular oxygen homeostasis and the pathophysiological consequences of excessive oxygen use. In addition, we provide an overview of findings from clinical studies on oxygen therapy for myocardial ischaemia, cardiac arrest, heart failure and cardiac surgery. These clinical studies have prompted a shift from liberal oxygen supplementation to a more conservative and vigilant approach to oxygen therapy. Furthermore, we discuss the alternative therapeutic strategies that target oxygen-sensing pathways, including various preconditioning approaches and pharmacological HIF activators, that can be used regardless of the level of oxygen therapy that a patient is already receiving.

Evaluation of the Effect of New Multimodal Analgesia Regimen for Cardiac Surgery: A Prospective, Randomized Controlled, Single-Center Clinical Study.

Objective: To investigate the feasibility of multimodal regimen by paracetamol, gabapentin, ketamine, lidocaine, dexmedetomidine and sufentanil among cardiac surgery patients, and compare the analgesia efficacy with conventional sufentanil-based regimen. Design: A single-center, prospective, randomized, controlled clinical trial. Setting: One participating center, the cardiovascular center of the major integrated teaching hospital. Participants: A total of 115 patients were assessed for eligibility: 108 patients were randomized, 7 cases were excluded. Interventions: The control group (group T) received conventional anesthesia management. Interventions in the multimodal group (group M) were as follows in addition to the standard of care: gabapentin and acetaminophen 1 hour before surgery; ketamine for induction and to maintain anesthesia with lidocaine and dexmedetomide. Ketamine, lidocaine, and dexmedetomidine were added to routine sedatives postoperatively in group M. Measurements and Main Results: The incidence of moderate-to-severe pain on coughing made no significant difference (68.5% vs 64.8%, P=0.683). Group M had significantly less sufentanil use (135.72µg vs 94.85µg, P=0.000) and lower rescue analgesia rate (31.5% vs 57.4%, P=0.007). There was no significant difference in the incidence of chronic pain, PONV, dizziness, inflammation index, mechanical ventilation time, length of stay, and complications between the two groups. Conclusion: Our multimodal regimen in cardiac surgery is feasible, but was not superior to traditional sufentanil-based regimen in the aspects of analgesia effects; however, it did reduce perioperative opioid consumption along with rescue analgesia rate. Moreover, it showed the same length of stay and the incidences of postoperative complications.

Fulminant lung fibrosis in non-resolvable COVID-19 requiring transplantation.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) can lead to the development of acute respiratory distress syndrome (ARDS). In some patients with non-resolvable (NR) COVID-19, lung injury can progress rapidly to the point that lung transplantation is the only viable option for survival. This fatal progression of lung injury involves a rapid fibroproliferative response and takes on average 15 weeks from initial symptom presentation. Little is known about the mechanisms that lead to this fulminant lung fibrosis (FLF) in NR-COVID-19. METHODS: Using a pre-designed unbiased PCR array for fibrotic markers, we analyzed the fibrotic signature in a subset of NR-COVID-19 lungs. We compared the expression profile against control lungs (donor lungs discarded for transplantation), and explanted tissue from patients with idiopathic pulmonary fibrosis (IPF). Subsequently, RT-qPCR, Western blots and immunohistochemistry were conducted to validate and localize selected pro-fibrotic targets. A total of 23 NR-COVID-19 lungs were used for RT-qPCR validation. FINDINGS: We revealed a unique fibrotic gene signature in NR-COVID-19 that is dominated by a hyper-expression of pro-fibrotic genes, including collagens and periostin. Our results also show a significantly increased expression of Collagen Triple Helix Repeat Containing 1(CTHRC1) which co-localized in areas rich in alpha smooth muscle expression, denoting myofibroblasts. We also show a significant increase in cytokeratin (KRT) 5 and 8 expressing cells adjacent to fibroblastic areas and in areas of apparent epithelial bronchiolization. INTERPRETATION: Our studies may provide insights into potential cellular mechanisms that lead to a fulminant presentation of lung fibrosis in NR-COVID-19. FUNDING: National Institute of Health (NIH) Grants R01HL154720, R01DK122796, R01DK109574, R01HL133900, and Department of Defense (DoD) Grant W81XWH2110032 to H.K.E. NIH Grants: R01HL138510 and R01HL157100, DoD Grant W81XWH-19-1-0007, and American Heart Association Grant: 18IPA34170220 to H.K.-Q. American Heart Association: 19CDA34660279, American Lung Association: CA-622265, Parker B. Francis Fellowship, 1UL1TR003167-01 and The Center for Clinical and Translational Sciences, McGovern Medical School to X.Y.

Jugular venous congestion during off-pump lung transplantation is not associated with an increased risk of postoperative delirium.

INTRODUCTION: Delirium occurs frequently after lung transplantation and is associated with poor clinical outcomes. Significantly prolonged jugular venous congestion (JVC) occurs during off-pump lung transplantation and is thought to impair cerebral perfusion. Our study aimed to test the hypothesis that increased intraoperative JVC is associated with an increased risk of postoperative delirium among lung transplantation recipients. METHODS: This is a retrospective observational cohort study. Adult patients who received off-pump lung transplantation at the Vanderbilt University Medical Center between 2006 and 2016 are included. The magnitude of JVC was calculated by the area under the curve (AUC) of the central venous pressure (CVP) above the threshold of 12 mmHg. Postoperative delirium was assessed by Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) criteria during their ICU stay. Multivariate regression analysis was used to determine the association of intraoperative JVC with postoperative delirium, adjusting for baseline demographics, surgical, and intraoperative characteristics. RESULTS: Thirty-two (23.5%) out of 136 patients developed delirium in the ICU. There was no statistical difference in terms of intraoperative JVC between patients with delirium and those without (4058 ± 6650 vs. 3495 ± 10 151 mmHg min; p = .772). Furthermore, during multivariate regression analysis, JVC was not associated with an increased risk of delirium (odds ratio: 1.03 per 100 mmHg min increase in venous congestion; 95% confidence interval: .31, 3.39; p = .96). CONCLUSIONS: Delirium occurred frequently after off-pump lung transplantation. Although physiologically plausible, the present study did not find an association between increased JVC during off-pump lung transplantation and an increased risk of postoperative delirium.

The Hypoxia-Adenosine Link during Myocardial Ischemia-Reperfusion Injury.

Despite increasing availability and more successful interventional approaches to restore coronary reperfusion, myocardial ischemia-reperfusion injury is a substantial cause of morbidity and mortality worldwide. During myocardial ischemia, the myocardium becomes profoundly hypoxic, thus causing stabilization of hypoxia-inducible transcription factors (HIF). Stabilization of HIF leads to a transcriptional program that promotes adaptation to hypoxia and cellular survival. Transcriptional consequences of HIF stabilization include increases in extracellular production and signaling effects of adenosine. Extracellular adenosine functions as a signaling molecule via the activation of adenosine receptors. Several studies implicated adenosine signaling in cardioprotection, particularly through the activation of the Adora2a and Adora2b receptors. Adenosine receptor activation can lead to metabolic adaptation to enhance ischemia tolerance or dampen myocardial reperfusion injury via signaling events on immune cells. Many studies highlight that clinical strategies to target the hypoxia-adenosine link could be considered for clinical trials. This could be achieved by using pharmacologic HIF activators or by directly enhancing extracellular adenosine production or signaling as a therapy for patients with acute myocardial infarction, or undergoing cardiac surgery.

Leadership roles and initiatives for diversity and inclusion in academic anesthesiology departments.

A cultural change in medicine has placed a renewed focus on the importance of a diverse and inclusive healthcare workforce. The methods employed by anesthesiology departments in pursuit of diversity and inclusion needs to be examined. OBJECTIVE: This study's objective was to assess the frequency of established leadership infrastructures and initiatives that promote diversity and inclusion within academic anesthesiology departments. DESIGN: This was a cross-sectional survey study. The authors emailed an electronic survey to 98 academic anesthesiology departments to assess leadership roles, dissemination platforms and initiatives used to support diversity and inclusion. SETTING: Academic anesthesiology department in the United States with at least 60 residents. MAIN OUTCOME AND MEASURES: The measure tested was the existence and quantification of leadership roles and initiatives directed at diversity and inclusion efforts at academic anesthesiology departments. RESULTS: The survey response rate was 49.4% (95% CI 39.3-59.6%). While 62.5% (95% CI 47.0-75.8%) of respondents reported having faculty members with a diversity and inclusion role, only 27.5% (95% CI 16.1-42.8%) reported a clearly defined leadership role such as vice-chair or committee chair. Seventy percent of respondents reported initiatives geared towards diversity using multiple platforms to showcase these initiatives. CONCLUSIONS: Based on these survey results, many anesthesia departments have developed initiatives to promote their departmental diversity. However, only a minority have established clearly defined leadership roles, which may be critical to enhance departmental success in promoting diversity and inclusion.

Incidence and Predictive Factors of Acute Kidney Injury After Off-pump Lung Transplantation.

OBJECTIVES: To determine the incidence and predictive factors of acute kidney injury (AKI) after off-pump lung transplantation. DESIGN: A retrospective cohort study. SETTING: The operating room and intensive care unit. PARTICIPANTS: Adult patients who underwent lung transplant without cardiopulmonary bypass or extracorporeal membrane oxygenator between 2006 and 2016 at the Vanderbilt University Medical Center. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The presence of postoperative AKI was assessed by the Kidney Disease: Improving Global Outcomes criteria in the first seven postoperative days. Multivariate logistic regression analysis was used to determine the independent predictive factors of AKI. One hundred forty-eight patients were included in the final analysis, of whom 63 (42.6%) subsequently developed AKI: 43 (29.0%) stage 1, ten (6.8%) stage 2, and ten (6.8%) stage 3. Patients who had AKI had a longer hospital length of stay (12 days [interquartile range (IQR): 10-17] vs ten days [IQR: 8-12], p < 0.001). For every one-year increase in age, the odds of AKI decreased by 8% (odds ratio [OR] 0.92, 95% confidence interval [CI]: 0.87-0.98, p = 0.008). The odds of having AKI in patients with bilateral lung transplant was lower than patients with unilateral transplant (OR 0.09, 95% CI: 0.01-0.63, p = 0.015). Additionally, a diagnosis of chronic obstructive pulmonary disease increased the odds of AKI by four-fold compared with a diagnosis of idiopathic pulmonary fibrosis (OR 4.73, 95% CI: 1.44-15.56, p = 0.011). CONCLUSIONS: AKI is a common complication after off-pump lung transplantation and is associated with increased hospital length of stay. Younger age, unilateral lung transplant, and diagnosis of chronic obstructive pulmonary disease are independently associated with AKI.

Intraoperative Management for Left Ventricular Assist Device Implantation With Concurrent Laparoscopic Sleeve Gastrectomy: A Case Series.

The increasing coincidence of obesity with heart failure may preclude eligibility for orthotopic heart transplantation, requiring continuous-flow left ventricular assist devices (LVADs) as destination therapy. This report describes intraoperative considerations for patients who underwent LVAD implantation with concurrent laparoscopic sleeve gastrectomy (LSG) to promote weight loss. In particular, right ventricular dysfunction associated with acute left ventricular unloading may be compounded by pneumoperitoneum for LSG due to the difficulty in ventilating patients with obesity, hypercarbia-mediated increase in pulmonary vascular resistance, and variable cardiac loading conditions. We identify specific anesthetic challenges and discuss methods of monitoring and management.

Catastrophic Cardiac Events During Transcatheter Aortic Valve Replacement.

BACKGROUND: Perioperative complications of transcatheter aortic valve replacement (TAVR) are decreasing but can be catastrophic when they occur. Systematic reports of the nature of these events are lacking in the contemporary era. Our study aimed to report the incidence, outcomes, and perioperative management of catastrophic cardiac events in patients undergoing TAVR and to propose a working strategy to address these complications. METHODS: This is a retrospective cohort study of patients who developed catastrophic cardiac events during or immediately after TAVR between 2015 and 2019 at a single academic centre. RESULTS: Of 2102 patients who underwent TAVR, 51 (2.5%) developed catastrophic cardiac events. The causes included cardiac perforation and tamponade (n = 19, 37.3%), acute left- ventricular failure (n = 10, 19.6%), coronary artery obstruction (n = 10, 19.6%), aortic-root disruption (n = 7, 13.7%), and device embolization (n = 5, 9.8%). Twenty-four patients (47.0%) with catastrophic cardiac events required stabilization by either intra-aortic balloon counter-pulsation or extracorporeal membrane oxygenation. The in-hospital mortality rate increased by 11.7-fold for patients with catastrophic cardiac events compared with those without (25.5% vs 2.0%, P < 0.001). Patients who developed aortic root disruption had the highest mortality rate (42.8%) compared with the others. The incidence of catastrophic cardiac events remained stable over a 5-year period, but the associated mortality decreased from 38.5% in 2015 to 9.1% in 2019. CONCLUSIONS: Catastrophic cardiac events during TAVR are rare, but they account for a dramatic increase in perioperative mortality. Early recognition and development of a standardized perioperative team approach can help manage patients experiencing these complications.