Faculty Bibliography

BACKGROUND:Studies have not explored consciousness during deep hypothermic circulatory arrest (DHCA). However, as studies in cardiac arrest have identified a spectrum of consciousness, we sought to establish the feasibility of studying consciousness during DHCA. METHODS:This was a prospective study across 10 hospitals with 36 DHCA patients undergoing thoracic aortic aneurysm repair or pulmonary endarterectomy. A tablet computer delivered audiovisual stimuli (images and names of three fruits) using headphones during each procedure as a potential test of implicit learning and explicit recall. We also established electroencephalography (EEG) and near-infrared spectroscopy (NIRS) to measure electrocortical markers of consciousness and cerebral oxygenation. Post-procedure interviews were carried out to test patients' ability to recall the audiovisual stimuli as well other explicit memories. PRIMARY OUTCOMES/METHODS:1) Feasibility of establishing tests of explicit recall and implicit learning, 2) Electroencephalography testing during DHCA. SECONDARY OUTCOMES/RESULTS:1) Signs of explicit recall of memories or implicit learning, and 2) identification of electrocortical biomarkers of consciousness during DHCA. RESULTS:Overall, 29/36 (81%) had the tablet set up. All 36 had NIRS and EEG set up, but 9 (25%) had useable EEG data, and 23 (66%) NIRS data. Delta EEG waves were observed during circulatory arrest in 3/9 (33%) patients, while 1/9 (11%) had theta waves just prior to circulatory arrest. All others showed isoelectric pattern. 35/36 (97%) agreed to follow up interviews. None had explicit recall of the names of the three fruits, but 3/36 (9%) correctly guessed them as a potential sign of implicit learning and 3 (9%) recalled other memories including events around the procedure and themes consistent with a recalled experience of death. CONCLUSIONS:A spectrum of consciousness and awareness, including signs of implicit learning and electrocortical biomarkers of consciousness may be present during DHCA, despite absence of visible signs of consciousness. This can be further used to help explain the negative psychological outcomes that cardiac arrest survivors face.

Cardiolipin (CL), the signature phospholipid of mitochondria, carries four fatty acids that are remodeled after de novo synthesis. In yeast, remodeling is accomplished by the joint action of Cld1, a lipase that removes a fatty acid from CL, and Taz1, a transacylase that transfers a fatty acid from another phospholipid to monolyso-CL. While taz1 homologues have been identified in all eukaryotes, cld1 homologues have remained obscure. Here we demonstrate that ABHD18, a highly conserved protein of plants, animals, and humans, is functionally homologous to Cld1. Knockdown of Abhd18 decreased the concentration of monolyso-CL in murine, Taz-knockout myoblasts. Inactivation of Abhd18 in Drosophila substantially increased the abundance of CL. Abhd18 inactivation also reversed the increase in the rate of CL degradation, as measured with ¹³C isotopes, and the accumulation of deacylated CLs, such as monolyso-CL and dilyso-CL, in TAZ-deficient flies. CL species with more than 5 double bonds were resistant to ABHD18. Our data demonstrate that ABHD18 is the elusive lipase that hydrolyzes CL in mice and flies and presumably in other organisms. Rather than removing just one fatty acid, we show that ABHD18 deacylates CL further. Thus, ABHD18 catalyzes the breakdown of CL whereas TAZ protects CL from degradation.

Barth syndrome is a mitochondrial disorder with hallmarks of cardiac and skeletal muscle weakness. Barth syndrome is caused by mutation of the X-linked gene Taz, required for cardiolipin remodeling. Previously described germline and conditional Taz knockout models are not ideal for therapeutic development because they lack the combination of robust survival to adulthood, cardiomyopathy, and skeletal muscle weakness. We characterized a cardiac and skeletal muscle-specific Taz knockout model (TazmKO) in which Cre recombinase is expressed from the muscle creatine kinase promoter (mCK-Cre). TazmKO mice survived normally. Cardiolipin composition was abnormal in both heart and skeletal muscle. TazmKO had reduced heart function by 2 months of age, and function progressively declined thereafter. Reduced treadmill endurance and diminished peak oxygen consumption were evident by three months of age, suggesting reduced skeletal muscle function. Electron microscopy showed abnormalities in mitochondrial structure and distribution. Overall, TazmKO mice display diminished cardiac function and exercise capacity while maintaining normal survival. This model will be useful for studying the effects of Taz deficiency in striated muscles and for testing potential therapies for Barth Syndrome.

Vasoplegic syndrome, a form of distributive shock that may manifest during or after cardiopulmonary bypass, is a serious complication that increases morbidity and mortality after cardiac surgery. No consensus definition exists, but vasoplegic syndrome is generally described as a state of pathologic vasodilation causing hypotension refractory to fluid resuscitation and vasopressor therapy, and resulting in organ malperfusion despite a normal or increased cardiac output. Diagnosis can be complex as there is a broad differential diagnosis for low systemic vascular resistance in the cardiac surgical patient. Interpretation of hemodynamic data can also be challenging in the setting of mixed shock states and mechanical support. This narrative review summarizes the pathophysiology of vasoplegic syndrome, the literature concerning its incidence and risk factors, the hemodynamic parameters important to the diagnosis of vasoplegic syndrome, a consensus definition of the syndrome, and a proposed goal-directed treatment framework.

The presence of underrepresented minorities (URMs) in cardiothoracic anesthesiology is underwhelming, and progress toward diversity has been slow at best. Despite decades of efforts, change seems hard to achieve. For example, it took more than 30 years for women to make up 50% of medical school matriculants. However, women continue to be underrepresented in our professional subspecialty and notably. This slow movement is not idiosyncratic to women but also applies to equity related to race and ethnicity. Given this current state, this article seeks to bring attention to the lack of diversity in cardiac anesthesiology and is a call to action to accelerate efforts and the pace of change toward greater equity both in our field and in medicine in general. This piece is the final part of a 4-part series exploring opportunities for improving diversity in cardiac anesthesiology. The authors focus specifically on the professional experience of URMs in medicine in our subspecialty and the opportunities for improving diversity. While many barriers for URM physicians reflect those of women, the experience of URM practicing physicians is unique and solutions need to incorporate.

OBJECTIVES/OBJECTIVE:This study aims to characterize the risks and benefits of in-OR extubation after cardiac surgery. DESIGN/METHODS:This is a retrospective chart review. SETTING/METHODS:Single tertiary care hospital. PARTICIPANTS/METHODS:Cardiac surgical patients >18 years. Exclusion criteria included patients extubated after 6 h in the ICU, those with a history of congenital heart disease (CHD), those intubated prior to arrival to the OR, procedures including circulatory arrest and/or selective cerebral perfusion, cardiothoracic transplantation, and intraoperative death. De-identified data was collected via the hospital's electronic medical record. INTERVENTIONS/METHODS:None. MEASUREMENTS AND MAIN RESULTS/RESULTS:Perioperative data was collected for 726 patients, of which 303 (42 %) were extubated in the OR. Multivariable regression models were derived with covariates based on expert clinical reasoning. When compared to fast track extubation, in-OR extubation was independently associated with decreased index hospitalization length of stay (-1.74, 95 % CI [-2.22, -1.08], p < 0.001) and decreased incidence of in-hospital new post-operative atrial fibrillation (OR 0.56 95 % CI [0.37, 0.86], p < 0.01). There were no differences in persistent vasoactive therapy requirement, postoperative mechanical circulatory support or extubation failure. CONCLUSIONS:In-OR extubation is associated with decreased index hospitalization length of stay and decreased new onset in-hospital atrial fibrillation.

BACKGROUND:Mitral leaflet elongation is common in hypertrophic cardiomyopathy (HCM), contributes to obstructive physiology, and presents a challenge to dual surgical goals of abolition of outflow gradients and mitral regurgitation. Anterior leaflet shortening, performed as an ancillary surgical procedure during myectomy, is controversial. METHODS:This was a retrospective study of all patients undergoing myectomy from 1/2010 to 3/2020 analyzing survival and echocardiographic results. We compared outcomes of patients treated with myectomy and concomitant mitral leaflet shortening with patients treated with myectomy alone. Over this time technique for mitral shortening evolved from anterior leaflet plication to residual leaflet excision (ReLex). RESULTS:Myectomy was performed on 416 patients age 57.5±13.6 years, 204 (49%) female. Average follow up was 5.4±2.8 years. Survival follow-up was complete in 415. Myectomy without valve replacement was performed in 332 patients, of whom 192 had mitral valve shortening (58%). Mitral leaflet plication was performed in 73, ReLex in 151 and both in 32. Hospital mortality for patients undergoing myectomy was 0.7%. At 8 years, cumulative survival was 95% for both myectomy plus leaflet shortening and myectomy alone groups, with no difference in survival between the two. There was no difference in survival between anterior leaflet plication and ReLex groups. Echocardiography 2.5 years after surgery showed a decrease in resting and provoked gradients, mitral regurgitation and left atrial volume and no difference in key variables between ancillary leaflet shortening and myectomy alone patients. CONCLUSIONS:These results affirm that mitral shortening may be an appropriate surgical judgment for selected patients.