key: cord-0754803-uz3p5yu5 authors: Martin, Archer Kilbourne; Weiner, Menachem M.; Feinman, Jared W.; Bhatt, Himani V.; Fritz, Ashley Virginia; Townsley, Matthew M.; Sharma, Archit; Stawiarski, Kristin; Patel, Saumil J.; Zhou, Elizabeth Y.; Addis, Dylan R.; Ghofaily, Lourdes Al; Malhotra, Anita K.; Teixeira, Miguel T.; Subramani, Sudhakar; Arora, Lovkesh; Cowart, Christopher R.; Jayaraman, Arun L.; Ramakrishna, Harish title: The Year in Cardiothoracic and Vascular Anesthesia: Selected Highlights from 2020 date: 2020-10-21 journal: J Cardiothorac Vasc Anesth DOI: 10.1053/j.jvca.2020.10.031 sha: 6b8accfe75352e3b16af809ceaf5f40b33c3765d doc_id: 754803 cord_uid: uz3p5yu5 This special article is the thirteenth in an annual series for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the editor-in-chief, Dr. Kaplan, and the editorial board for the opportunity to continue this series, namely the research highlights of the past year in the specialty of cardiothoracic and vascular anesthesiology.(1) The major themes selected for 2020 are outlined in this introduction, and each highlight is reviewed in detail in the main body of the article. The literature highlights in the specialty for 2020 begin with an update on valvular disease, with a focus on updates in management of aortic and mitral valve disorders. The second major theme is an update on coronary artery disease, with discussion of both medical and surgical management. The third major theme is focused on the perioperative management of COVID-19 patients, with the authors highlighting literature discussing medical, surgical, and anesthetic considerations for their cardiac care. The fourth major theme is an update in heart failure, with discussion of medical, psychosocial, and procedural aspects of this complicated disease process. The fifth, and final theme, focuses on the latest analyses regarding survival in heart transplantation. The themes selected for this thirteenth special article are only a few of the diverse advances in the specialty during 2020. These highlights will inform the reader of key updates on a variety of topics, leading to improvement of perioperative outcomes for patients with cardiothoracic and vascular disease. Transcatheter valve replacement; Transcatheter valve repair; Coronary artery disease; Left ventricular assist device; Cardiothoracic transplantation; Heart transplantation; COVID-19 Valvular heart disease affects a significant percentage of the population and remains one of the most common reasons for consultation with a cardiologist or cardiac surgeon. 2 Research is ongoing in an effort to better understand which cohort of patients will benefit from traditional surgical therapies versus minimally invasive approaches and which patients should be managed with medical therapy alone. Over the past year, there have been a number of prominent studies addressing these important concerns. Aortic stenosis (AS) remains one of the most commonly encountered cardiac pathologies in the elderly populations and is associated with significant morbidity and mortality. 3 Current practice guidelines for patients with severe symptomatic aortic stenosis or patients with severe AS (aortic valve area < 1.0cm2) and left ventricular systolic dysfunction (LVSD) are well established and recommend aortic valve replacement (AVR) for this patient population. 4, 5 Guidelines for surgical therapies in moderate AS currently recommend consideration of AVR only when the patient is undergoing cardiac surgery for another indication, however, these are not as well established and require further investigation. 4 Previous studies, including those by van Gils and colleagues 6 and Delesaale and colleagues 7 , found that moderate AS with or without concomitant heart failure is not as benign as previously thought, thus raising the question 4 regarding the potential benefit of AVR in this patient population. However, nearly all relevant studies have had limited numbers of patients and/or short-term follow-up. Therefore, there remained a gap in the literature for more definitively understanding the prognostic impact of increasing severity of AS to better guide the clinical management of these patients. Strange and colleagues sought to answer this question using data from the Australian National Echocardiography Database. 8 Out of a total of 122,809 male patients (mean age 61 ± 17 years) and 118,494 female patients (mean age 62 ± 19 years) with measured AV hemodynamics, 16 ,129 (6.7%), 3,315 (1.4%), and 6,383 (2.6%) patients had mild, moderate, and severe AS, respectively. The median follow-up was 1,208 days. Not surprisingly, they found that increasing severity of AS was associated with worse 1-year and 5-year mortality. However, what was more provocative was the finding that there was a clear dichotomy of risk in overall survival using age-and gender-adjusted Cox regression models, with no AS (reference) and mild AS (hazard ratio [HR] 1.02; 95% CI, 0.98-1.07; p = 0.32) having similar risk profiles and moderate AS (HR 1.19; 95% CI, 1.12 -1.26; p < 0.001) and severe AS (HR 1.22; 95% CI, 1.13-1.31; p < 0.001) having similar risk profiles. The overall 5-year mortality was 56% and 67%, respectively, in those with moderate AS (mean gradient 20.0 to 39.0 mm Hg/peak velocity 3.0 to 3.9 m/s) and severe AS (≥40.0 mm Hg, ≥4.0 m/s, or AV area <1.0 cm2 in low-flow, low-gradient severe AS). The authors found that the threshold of increased risk of longer-term all-cause and valve-related mortality was at approximately a mean AV gradient of 20.0 mm Hg and an equivalent peak AV velocity of 3.0 m/s. The authors concluded that there needs to be a re-evaluation of the 5 prognostic impact of moderate AS and the potential value of more timely interventions to reduce a high risk of mortality in the medium to longer term. While the study is not without its limitations including a lack of adjustment for comorbidities, this study has laid an important foundation for future studies on the prognostic effects of moderate AS and its management. Additionally, it is still unclear from this study if moderate AS patients will benefit from AVR. As we continue to see advancements in minimally invasive cardiac surgery, we encounter debates comparing newer versus traditional surgical approaches to treat a wide range of cardiac pathologies. Moscarelli and colleagues compared traditional median sternotomy to a minimally invasive approach for repair of complex mitral valve disease (MVD), specifically bileaflet and Barlow"s mitral valve disease. 9 They specifically examined how each approach affected the long-term outcomes of these patients by seeing if either technique was more or less likely to result in moderate mitral regurgitation (MR) or mitral valve re-operation over a period of up to 10 years. This information had previously been looked at in several single center studies at high volume centers and found no difference between the two approaches. 10, 11 The authors used a pooled meta-analysis of studies reporting follow-up of mitral valve repair (MVR) for complex mitral valve regurgitation and looked at two outcomes. The primary outcome was recurrence of MR and need for re-operation, while the secondary outcomes were operation time, reopening for bleeding, associated tricuspid procedures, failed repair, and inhospital mortality. Eighteen studies involving over 1,900 patients were used in total, and no 6 significant differences were found between MR recurrence and need for re-operation between minimally invasive and sternotomy groups (1.7% [95% confidence interval, 1.0% to 2.9%] vs 1.3% [95% confidence interval, 0.9% to 1.8%], P=0.22). There were also no statistically significant differences in secondary outcomes. Of note, the minimally invasive group was associated with longer aortic cross-clamp and cardiopulmonary bypass times (p<0.01). Despite these compelling results, there is likely to still be a considerable amount of resistance to move towards a minimally invasive approach to treating complex mitral valve disease. There are a few reasons for this lack of acceptance. The first is the potential for adding unnecessary complexity to an otherwise straightforward operation. Minimally invasive techniques, while advancing, are still technically difficult to perform and likely to add complexity without any known functional long term benefit to the patient. 12 Second is the goal of a curative operation without encountering complications. Many patients with complex mitral valve disease are young and otherwise healthy. As such, they are likely to be cured of their disease with a successful operation. 13 So, the question remains -should physicians give up a definitive treatment in an effort to move towards a minimally invasive approach for the possibility of better aesthetics and one less day in the hospital? Finally, we do not have data beyond 10 years for these patients. 10 Many proponents of traditional sternotomy approach note that minimally invasive approaches may not adequately address complex valve lesions with large myxomatous tissue or annular calcifications. These issues may arise when longer term data becomes available in the future. 12 Despite this hesitancy to move away from traditional approaches to fixing conditions such as complex mitral valve disease, we must be aware of the fact that there is a clear interest in 7 treating more severe conditions with a minimally invasive approach. 14 Percutaneous techniques have shown some success in treating a wide array of cardiac conditions and will continue to evolve over time. As such, there is a growing need for investigations that compare long term outcomes of each approach in order to feel confident that more complex conditions can be addressed in a minimally invasive fashion. 14 Calcification MVD in patients with mitral annular calcification (MAC) has long been a difficult pathology to treat. Due to the difficult anatomy associated with MAC, surgical options have traditionally been limited, as replacement of these valves can commonly lead to fatal atrioventricular groove disruption and paravalvular leak. 15 Moreover, many patients who have MVD and MAC are commonly found to have numerous other comorbidities, making them less than ideal surgical candidates and therefore are often deemed to be too high risk for surgery. 16 Fortunately for these patients, new techniques are on the horizon that may present less invasive options for MVR in patients with severe MAC. Sorajja and colleagues describe using a new, anatomically designed mitral prosthesis (Tendyne prosthesis-Abbot Structural, Santa Clara, California) utilizing a transcatheter approach for MVR to treat patients with MR and severe MAC. 18 The valve is a self-expanding, fully retrievable and repositionable valve that is implanted via a transapical approach. A total of 9 patients with a mean age of 77 years old were recruited for this study at 5 different medical centers. Study participants had to meet 4 different inclusion criteria, including symptoms of heart failure, severe MR (defined using standard American Society of Echocardiography criteria), severe MAC and prohibitive surgical risk. Of note, patients with severe left ventricle (LV) dysfunction, severe tricuspid regurgitation, or pulmonary hypertension were excluded. The authors reported complete relief of MR in all 9 patients, stating that 7 of them required balloon valvuloplasty prior to deployment of the prosthetic valve. They reported no device embolization, no post-procedural mitral gradient, and no patients required the use of extracorporeal circulation or other invasive hemodynamic support. One case resulted in technical failure due to left ventricular outflow tract (LVOT) obstruction after the prosthetic valve became malrotated. This patient later underwent alcohol septal ablation and ultimately suffered a post-operative cardiac arrest, leading to end organ damage and an eventual hospice admission. Another patient subsequently developed a hemothorax requiring drainage. Of the 9 patients, 5 were ultimately sent directly home, while 4 were discharged to a nursing facility. Long-term clinical follow up was carried out over 28 months. One patient, described above, passed away on postoperative day 41 in hospice, while another died of suicide 8 months 9 after the trial was completed. The remaining 7 patients were free of MR and saw improvement in their symptoms. Two of the study participants were ultimately admitted to the hospital for heart failure during the follow up period. The authors reported no incidence of major adverse clinical events. This investigation by Sarajja and colleagues is an optimistic outlook for the future in terms of transcatheter mitral valve replacement for patients with severe MR and MAC. While this is a small case series with strict inclusion criteria, it goes on to highlight some of the potential benefits of utilizing these techniques in high-risk populations, and certainly demonstrates the feasibility to provide relief for these patients. Coronary artery disease (CAD) is a significant source of both morbidity and mortality within the adult population worldwide. 19 The spectrum of treatment spans from medical management to a range of invasive procedural and surgical options. Studies highlighted include updates from major studies covering the entire scope of these clinical concerns. The question as to when, if at all, stable coronary disease should be intervened upon is one that has been examined in many small and large trials without a definitive conclusion being reached. Several large-scale clinical trials of stable ischemic heart disease have demonstrated the effectiveness of lifestyle and pharmacologic interventions in reducing the likelihood of major adverse cardiac events. However, many patients still undergo routine cardiac catheterization and revascularization for stable disease, which have not been demonstrated to confer any mortality benefit. [20] [21] [22] [23] The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) study sought to address this conundrum, and its initial results were published in the New England Journal of Medicine in 2020. 24 This study enrolled patients with stable coronary disease and moderate-severe ischemia, randomizing them to an initial invasive strategy of angiography and revascularization plus optimal medical therapy or an initial conservative strategy of optimal medical therapy with the option for later intervention. 25 A total of 5,179 patients were enrolled at 320 sites across 37 countries, with a primary composite outcome of death from cardiovascular causes, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. The authors found no difference between the initial aggressive and conservative management groups with respect to the primary composite outcome over a median of 3.2 years (event rate of 16.4% and 18.2% at 5-years, respectively, 95% CI -4.7 to 1.0). The study also examined a secondary outcome of death from cardiovascular causes or MI and similarly found no significant difference between the two groups. One methodological issue raised by the study findings is how a study examining coronary disease defines "myocardial ischemia." In the ISCHEMIA trial, patients with a positive stress test underwent coronary computed tomographic angiography (CCTA) to diagnose the presence of coronary disease. The trial did not routinely use fractional flow reserve (FFR) during catheterization as part of its definition, which is more sensitive to lesion-specific ischemia detection and was shown in a previous trial to significantly reduce death, myocardial infarction, and repeat revascularization. 26 The effect of the completeness and method of revascularization was also not addressed in the initial outcomes of the ISCHEMIA trial, nor were any quality-of- 11 life metrics that may have led towards a greater rate of intervention. While there are surely more data to come from this trial and others on conservative management versus revascularization, the initial results from ISCHEMIA point towards conservative medical therapy as a viable treatment path for at least a subset of patients with stable coronary disease. were randomized between PCI and CABG, and five-year outcome data were recently published. 28 At five years, the authors found no difference in the primary composite outcome of death from any cause, stroke or MI between the PCI and CABG groups (22.0% vs 19.2%, 95% CI -0.9 -6.5, p=0.13). There was, however, a change in whether PCI or CABG was favored depending on the time interval examined within the study. At 30 days, the primary outcome favored PCI (HR 0.61, 95% CI 0.42-0.88), from 30 days to 1 year PCI and CABG were equivalent (HR 1.07, 95% CI 0.68-1.70), and from 1 to 5 years the primary outcome favored CABG over PCI (HR 1.61, 95% CI 1.23-2.12). 28 The rate of MI alone was higher in the CABG group during the first 30 days, but was subsequently higher in the PCI group from 1 to 5 years which explains some of this temporal difference; however, the overall rate of MI at 5 years was not different between the two groups. These findings somewhat contradict other recently published data examining PCI vs CABG in left main disease. The NOBLE trial, which also used a second-generation drug-eluting stent for PCI, found a significantly increased risk of major adverse cardiac events (all-cause mortality, non-procedural MI, repeat revascularization and stroke) in the PCI group at five years, driven mainly by non-procedural MI and need repeat revascularization. 29 Another recently published meta-analysis, which included 4,595 patients with left main disease undergoing PCI or CABG, found no difference in all-cause mortality at five years, but rates of MI, repeat revascularization, and major adverse cardiac events all favored CABG for treatment of left main disease over PCI. 30 It is important to note that the large number of procedural variables between the mentioned studies, including type of stent, off-pump vs on-pump CABG, number of arterial grafts, and post-operative care protocols, makes direct comparisons challenging. Nonetheless, while reported mortality rates between PCI and CABG were similar at five years, these studies suggest that the early stroke and peri-procedural MI risk in CABG must be weighed against a longer-term increased risk of MI and need for repeat revascularization following PCI. Surgical coronary revascularization through CABG reestablishes coronary blood flow and thus restores myocardial oxygen supply, but does not treat the underlying coronary 13 atherosclerosis. Likewise, CABG does not prevent the continued progression of atherosclerosis in the native coronary arteries or the development of disease in the new bypass grafts. Instead, it is medical therapy instituted following CABG or stenting that attempts to arrest or slow CAD progression. Ultimately, the objective of secondary prevention is to achieve more durable CABG results, decrease the need for repeat interventions, reduce hospitalizations, improve functional status, and decrease mortality. Guidelines from Europe and North America emphasize the importance of prompt postoperative initiation and continued maintenance of key secondary prevention therapeutics in appropriate patients, including antiplatelet medications, statins, reninangiotensin-aldosterone system (RAAS) inhibitors, and beta-blockers. 31, 32 Data from Swedish national registries, including the SWEDEHEART Registry (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies), suggest that pharmacy dispensation rates for several of these critical secondary-prevention medications decrease over time with a corresponding increase in mortality. 33 These registry data included 28,448 patients admitted for first-time CABG between 2006 and 2015, with medication exposure status established at 6 months after discharge and updated every 3 months. The median follow-up time in this study was 4.9 years. While baseline dispensation rates were high, this decreased over time, dropping from 93.9% to 77.3% for statins, 91% to 76.4% for beta-blockers, 72.9% to 65.9% for RAAS inhibitors, and 93% to 79.8% for antiplatelet drugs. After adjusting for confounders, the authors found a significant inverse association between all-cause mortality and use of statins, RAAS inhibitors, and antiplatelet drugs. Interestingly, the authors found no association between the rate of beta-blockers dispensation and the risk of mortality. Low-income patients had statins and antiplatelet medications dispensed less often, both at baseline and at 8 years, than those with 14 higher incomes, and had a steeper decline in dispensation rate over time. There are important limitations inherent to the retrospective design of this study, including the inability to determine causality. As the authors point out, numerous risk factors could not be accounted for, including lifestyle factors such as tobacco use, exercise habits, and diet. The application of these reported data to other countries is buttressed by two key points that are not unique to cardiovascular medicine -the beneficial health impact of consistent compliance by patients and physicians with evidence-based treatments as well as the ongoing need to improve cardiovascular outcomes across the spectrum of socioeconomic circumstances. The benefit of using a left internal thoracic artery graft in addition to venous grafts for CABG has been well-established, and is thought to be due to the superior patency of the arterial conduit. As such, several observational studies have been performed comparing bilateral internal thoracic artery grafts (BIMA) to single internal thoracic artery grafts (SIMA) for CABG, and have demonstrated improved long-term mortality when multiple arterial conduits are used. 34, 35 The Arterial Revascularization Trial (ART) sought to address this question by means of a multicenter randomized control trial. The authors selected patients with multi-vessel coronary disease who were scheduled to undergo CABG and randomized them to receive either single or bilateral internal thoracic artery grafting plus any additional venous grafts that were deemed necessary. The initial 5 year data from the ART trial showed no difference between the two groups in either all-cause mortality or the composite outcome of death from any cause, MI, or stroke. 36 The ART trial group recently published the 10-year follow-up outcomes of the study. 15 At 10 years, there continued to be no significant difference between the two groups in allcause mortality or the composite outcome of death, stroke, MI, or need for repeat revascularization. 37 However, there were some significant confounding factors in this trial that must be addressed. First, there was a high rate of crossover between the two groups, with 14% of the BIMA group receiving only a single IMA graft and 2% of the SIMA group receiving BIMAs. Perhaps more significantly, 22% of the SIMA group also received a second arterial conduit in the form of a radial artery graft. As radial artery grafts, similar to IMA grafts, have a longer expected patency than venous grafts, the nearly one-fifth of SIMA patients who received two arterial grafts likely had a significant effect on the ability to detect any statistically significant difference between the two groups. Indeed, when the data were analyzed to compare those who received two or more arterial grafts to those who did not, there appeared to be a meaningful difference in mortality favoring multiple arterial conduits. Whereas the ART trial was neither designed nor powered to judge whether this difference was statistically significant, there is currently a trial underway that is designed to answer this very question. 38 Coronavirus Disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection is caused by binding of the viral surface spike protein to the human angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is expressed in the lung (principally type II alveolar cells) and is highly expressed in the heart as well, counteracting the effects of angiotensin II in states with excessive activation of the 16 renin-angiotensin system, such as hypertension, congestive heart failure, and atherosclerosis. 39 COVID-19 interacts with the cardiovascular system on multiple levels, with increasing morbidity and mortality observed in patients with underlying cardiovascular conditions. 40 Li and colleagues addressed the role of cardiovascular disease (CVD) in the progression and prognosis of COVID-19, reporting that COVID-19 patients with CVD showed more several clinical symptoms, lung injury, uncontrolled cytokine storm, and hypercoagulable state compared to patients without a history of CVD. 41 Additionally, studies have shown pre-existing CVD to predict mortality in COVID-19 pneumonia patients. [42] [43] [44] Cardiovascular damage secondary to COVID-19 includes a wide variety of clinical syndromes including myocarditis, cardiogenic shock, pulmonary embolism, and arrhythmias. These cardiac pathologies may also be caused or exacerbated by pharmacological therapies administered to treat COVID-19 infection. 45, 46 As of yet, no comprehensive expert recommendations regarding COVID-19 treatment in patients with pre-existing cardiovascular disease exist, but the input of dedicated multidisciplinary teams to guide selection has been widely recommended. Morawietz and colleagues suggested that patients with elevated troponin T and triglyceride levels should continue medications related to pre-existing cardiovascular comorbidities including antiplatelet therapy, beta blockers, and statins due to their potential to attenuate inflammation, acute lung injury, and cardiovascular complications. 47 Several potential negative drug interactions secondary to therapeutics are possible. First, anti-viral or immune response modulator medications may trigger ventricular arrhythmias via QTc interval prolongation. Second, patients with pre-existing disease receiving Angiotensin Receptor Blockers (ARBs) or Angiotensin Converting Enzyme Inhibitors (ACEs) have upregulation of ACE2, the binding site for SARS-CoV-2. However, this concern, derived from in vitro and animal studies, has not found confirmation in clinical practice. 48 The worldwide COVID-19 pandemic has had a profound impact on the delivery of cardiac surgical care throughout the world. 49, 50 Cardiac patient demographics show a predominant aged population with frequent co-morbidities, and are thus the highest risk for mortality associated with COVID-19. However, it is vital cardiac surgical teams balance the risk of delaying surgery versus increasing the likelihood of acquiring COVID-19 infection. The pandemic has also impacted the logistical operations of surgical care, and factors such as shortage of blood products, personal protective equipment (PPE), and limited inpatient hospital resources directed towards the pandemic need to be considered prior to utilization medical care facilities for elective cardiac surgery. Surgeons (STS) recommended templates for physicians and interdisciplinary teams to consider and adapt for their own individual medical center treatment strategies (Figure 1 ). Their recommendation for postponement of elective cardiac surgery is based on the following principles: protecting the patient, protecting the healthcare team, protecting the individual institution, and protecting society. 51 The template proposed a four-tier system for various cardiac services depending on the inpatient occupancy of COVID-19. If the inpatient load is less than 30%, minimal reduction in elective surgery is suggested. They also emphasize importance of collaboration between the cardiac surgical team and extracorporeal life support organization (ELSO) to provide extracorporeal support for certain COVID patients in an efficient way. 52 The implementation of a tiered system to manage cardiac surgical patients in the setting of the COVID-19 pandemic is seen in other literature as well. Patel and colleagues also provided both a perioperative testing algorithm for SARS-CoV-2 and recommendations for the perioperative care of cardiac surgical patients. 53 They proposed a three-tier system based on acuity of underlying cardiac disease as well as the pre-test probability of COVID-19 infection. In the setting of low acuity cases, their recommendations were to postpone surgery for up to 12 weeks. 53 Cardiac surgery hospitals in Italy"s Lombardy Region organized "Hub Centres" to minimized postponement of treatment for cardiovascular patients and "Spoke Centres" that served as satellites for efficient enrollment of patients seeking cardiac care. The Canadian Society of Cardiac Surgeons suggested a three-tier triage system based on reduction in their routine services, with a shift to emergency cardiac surgeries only if routine services are reduced by 50% or more due to COVID-19 patient surges. 50 The combination of high-frequency aerosol generating procedures (AGP) with the strong transmissibility of SARS-CoV-2 presents a novel challenge for anesthesiologists in preventing cross-contamination between equipment, personnel, and anesthetizing locations. SARS-CoV-2 has been proven to be transmitted through contact with infected surfaces and fluids, with possible aerosol transmission. 54, 55 Examples of AGP include bag-mask ventilation, intubation, extubation, airway suctioning, and cardiopulmonary resuscitation. Even though there is a lack of agreement between guidelines as to the use of airborne precautions during routine care, airborne precautions including the use of a fitted N95 mask or powered air purifier respirator (PAPR) are universally recommend for AGP. 56 Elective procedures are generally deferred in COVID-19 patients, thus resulting in the predominance of procedures presenting as emergencies. Operating room logistics should focus on efficient delivery of care with minimization of risk to the patient and healthcare staff. Intubation and extubation should be performed by the most experienced person with full airborne precautions available, ideally in an airborne isolation room that is configured for negative pressure protection relative to the surrounding area. Pre-oxygenation with 100% oxygen, followed by rapid sequence intubation, should be performed to reduce aerosolization with mask ventilation. In addition to extensive PPE amongst the anesthetic team, literature recommends the use of a high-efficiency anti-viral filter between the mask and breathing circuit. 57 All members of the healthcare team should be well-versed and practiced in the local protocols designed from the latest literature for initiation of care and transport of anesthetized COVID-19 patients. Despite numerous advances in therapy, heart failure continues to remain a significant and increasing problem. It is estimated that there are over 6 million patients with heart failure in the United States alone, accounting for 10% of deaths attributable to cardiovascular disease. 58 Mortality and resource utilization remain high with total costs projected to be almost $70 billion by 2030. 59 Some of these costs are directly attributable to implantation of mechanical circulatory support (MCS) devices. In 2019, INTERMACS reported implantation of over 25,000 devices, including left ventricular assist devices (LVAD), and 1-year survival with LVAD is over 80%. 60, 61 Highlights for 2020 include discussion of advancements in both device and medical management, two facets of heart failure management that are applicable to the perioperative arena. Due to increased survival and scarcity of organs for transplant, implantation of LVADs is becoming more and more common. Despite the high prevalence in the United States of mental illness in those with chronic health conditions such as heart failure, there has been a lack of research concerning device implantation in such patients. A recent study has therefore been the first to investigate psychiatric comorbidity and outcomes after LVAD implantation. 62 Using the INTERMACS database, Mullan and colleagues identified a total of 2,207 out of 22,000 patients who had a psychiatric comorbidity. In addition to having lower quality of life scores, an increase in adverse events of hospital readmission, thrombotic events, and infection were observed in this population. 62 As compared to the general population, the prevalence of psychiatric disease in LVAD patients within the database was lower, although a key limitation of the study is the illdefined nature of "psychiatric comorbidity" within the INTERMACS database. Despite the increase in morbidity, no increase in mortality was observed in patients with psychiatric comorbidities. 62 Despite the increasing implantation of LVADs within the heart failure population, the most commonly implanted MCS device remains the intra-aortic balloon pump (IABP). Historically, the most common insertion sites have been the femoral and subclavian arteries. Newer techniques have allowed percutaneous placement with fluoroscopic guidance via the axillary artery. 63, 64 Placement in the upper extremity is advantageous due to the ability of patients to ambulate as well as decreased rate of infections. A recent retrospective study evaluated 195 patients with advanced heart failure who received IABP support via the axillary route. 64 Outcomes evaluated were two-fold: The first was defined as successful heart replacement, including bridge to transplant or planned permanent MCS device. The second was defined as failed heart replacement, secondary to either death or unplanned upgrade in MCS. A total of 133 patients had successful cardiac replacement. The failure group consisted of 62 patients, with 16 deaths, 18 requiring escalation of therapy, and 28 who had the IABP removed for complications. Adverse events included cerebrovascular accidents (2.5%), left upper extremity ischemia (3.5%), and mesenteric ischemia due to malpositioning of the IABP (3%). Use of the axillary approach allowed longer usage and improved patient ambulation. The percutaneous approach allowed for non-general anesthetics to be used for placement, which may provide some benefit in the heart failure population. Treatment options for patients with heart failure with preserved ejection fraction (HFpEF) remain limited. After much success with the incorporation of angiotensin-neprilysin 22 inhibitors (ARNI) into mainstay therapy for heart failure with reduced ejection fraction (HFrEF), possible use in the HFpEF population is under exploration. Initial investigations began in 2012 with the PARAMOUNT study, a multi-center, phase II trial that enrolled patients with left ventricular ejection fraction ≥ 45% and New York Heart Association (NYHA) class II-III heart failure symptoms with elevated NT-pro BNP. 65 Patients were randomly assigned to receive LCZ686, an ANRI, or valsartan followed by a titration period to target doses of 200 mg and 160 mg twice daily, respectively. Primary endpoint was change in NT-proBNP from baseline to 12 weeks, with significant reduction seen in the LCZ696 group compared with the valsartan group (LCZ696: baseline, 783 pg/mL to 605 pg/mL compared with valsartan: 862 pg/mL to 835 pg/mL, p=0.005). LCZ696 was well tolerated with adverse effects similar to those of valsartan. 65 This favorable outcome provided the basis for the later 2019 PARAGON-HF trial that looked at a composite clinical outcome of total hospitalizations for heart failure and death from cardiovascular causes. 66 Patients were randomized to receive either sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). Enrolled patients had similar profiles to those in the PARAMOUNT trial including left ventricular ejection fraction ≥ 45% and New York Heart Association (NYHA) class II-III heart failure symptoms with elevated NT-proBNP. However, unlike PARAMOUNT, PARGON-HF patients were required to have evidence of structural heart disease. Approximately 35% enrolled patients had ischemic cardiomyopathy. Despite the previous reductions in NT-proBNP seen in PARAMOUNT, there was only a trend towards a reduction in the primary outcome (HR, 0.87, 95% CI, 0.75-1.01; p=0.06) which was largely driven by a 15% reduction in HF 23 hospitalizations and 5% reduction in cardiovascular causes of death. When reviewed in the context of 12 pre-specified subgroups, there was possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women. This heterogeneity in outcomes was not seen in the prior HFrEF trials which showed consistency across all patient groups. 67 However, PARAGON-HF does demonstrate the safety and general tolerability of the sacubitril-valsartan combination in this population. Current HF guidelines remain limited to the approved use of ARNI therapy in HFrEF alone. 68 Further studies are required to clarify select patient populations that may derive the best benefit from ARNI prior to expanding the ARNI use to HFpEF. Heart transplantation remains the gold standard of treatment for end-stage heart failure refractory to medical management or MCS devices. Given that recent literature has discussed the importance and emergence of anesthesiologists as members of cardiothoracic multi-disciplinary transplant teams, an understanding of the new allocation system and latest data regarding variables impacting cardiothoracic transplant survival is vital for our specialty to successfully integrate with other disciplines. 69, 70 Highlights for 2020 include updates on donor factors, recipient factors, surgical factors, and the effect of the new heart allocation system on survival. Survival after heart transplantation continues to improve, with a mean survival post- More recently, through temporal decomposition statistical analysis of a large retroactive cohort, Hsich and colleagues categorized post-transplantation mortality into early, constant, and late hazard phases. 71 The risk of death was greatest during the first week post-heart transplantation with a decline over 1 month, which was primarily influenced by both procedure related outcomes and the medical condition of the recipient. The constant phase of survival correlated with non-modifiable risk factors such as age, race, and socioeconomic factors. In the late phase, risk of death increased with time, diabetes, obesity, age, and transplantation complications. Using a 3 phase mortality paradigm allows for a more precise evaluation of timedependent risk factors for mortality. 71 Specific recipient, donor, and surgical characteristics are associated with increased posttransplantation mortality in cardiothoracic transplantation, and should be recognized to optimize organ allocation and clinical outcomes. 70, 72 Recipient end-organ dysfunction, including cardiac, hepatic, renal, or pulmonary failure, has the highest overall correlation with post-transplantation 25 mortality at 90 days. At 1-year, mortality is impacted by need for mechanical ventilation, advanced donor age, or donor ischemic time greater than 4 hours. 73 Late phase mortality, assessed at both 5 and 10 years, was most affected by recipient and donor ages. Interestingly, the detrimental effect of prolonged ischemic time without other donor risk factors does not impact the 5-year post-transplantation survival. 74 Overall, recipients who undergo transplantation for ischemic or non-ischemic cardiomyopathy have a better prognosis than those with congenital heart disease (HR 1.722, CI 1.40-2.12, p <0.01), restrictive cardiomyopathy (HR 1.363, CI 1.119-1.661, p <0.01), or re-transplantation (HR 1.671, CI 1.337-2.088, p <0.01). 73 The most consistent predictor of mortality in heart transplantation over time was an elevated recipient total bilirubin, with the greatest predictive value of this influencing factor observed in early posttransplantation. 75 Understanding recipient sex disparity in heart transplantation is complex, but paramount to ensure equitable therapy and organ allocation. Men and women are listed based on criteria that are not sex specific, yet sex specific interactions with strong predictors of mortality prior to heart transplantation have been elucidated. 76 Although sex mismatching of female donors to male recipients appears to result in increased mortality, overall post-transplant survival based on sex alone has yielded contradictory results. [76] [77] [78] Currently, female recipients only represent 1 in 4 heart transplants worldwide, and appear to receive hearts from higher risk donors. 79 This has been ascribed to women presenting with end-stage heart failure at an older age, selection, referral bias, and purported poorer outcomes in female recipients. 80-82 Female recipients, however, have significantly higher post-transplant survival than men (median 12.2 years versus 11.4 years, respectively). Two large retrospective cohort studies using international Registry data applied advanced statistical modelling as well as machine learning to address these conflicting results. 26 Both concluded that, when matched for recipient and donor characteristics, sex was not a significant variable predicting mortality in early post-operative, constant, or late survival of heart transplantation. 71, 79 Heart transplant survival has continually improved over time, yet complications such as graft failure, rejection, and cardiac allograft vasculopathy (CAV) can necessitate cardiac retransplantation. 73 Globally, approximately 120 cardiac retransplants are performed on a yearly basis, accounting for 2.2% of heart transplants performed in 2016. 75 Heart retransplant survival rates are lower both in 1 year ( Figure 2 ) and conditional 1 year survival as compared to all comers for index operation. 73, 83 Most commonly performed in the early phase for primary graft failure, CAV predominates etiology of retransplantation after the first month of primary transplant. 83 Barghash and colleagues recently provided an update on heart retransplantation outcomes, reporting that retransplant recipients are often younger, hospitalized at time of transplant, and more frequently required preoperative use of intravenous inotropic medications or MCS devices as compared to primary transplant patients. 83 They noted that while patients who have been bridged with MCS to retransplantation have historically suffered from lower survival rates, examining the latest data reveals similar outcomes in patients who are bridged at least 1 year post-initial transplant as compared to those who are retransplanted without MCS bridging. 83 In response to an increasing number of heart failure patients transitioned to MCS devices, stabilized hemodynamically, and discharged home to await cardiac transplantation, the United States heart transplantation organ allocation system was modified on October 18 th , 2018. Prior to this revision by the Organ Procurement and Transplantation Network"s (OPTN) Thoracic Organ Transplantation Committee and the United Network Organ Sharing (UNOS), the last revision was in 2000. The prior system arguably fostered an environment which allowed for regional and geographic inconsistencies in donor access as well as increased wait-list times for high-risk candidates. 84, 85 The old system utilized three tiers (Status 1A/B and Status 2) while the new system transitioned to Status 1-6 ( Table 1) while broadening geographic boundaries. 86 At first review, preliminary assessment of patients transplanted under the new system (through March 31 st , 2019) reported a decrease in wait-list mortality but unexpectedly poor posttransplant survival rates with an increase in retransplantation as compared to the old system. 87 Cogswell and colleagues emphasized that these early results represented a small sample size (n=529) and further evaluation was needed to determine trends in survival. 87 Jawitz and colleagues sought to build on these preliminary data and determine survival under the new system. 88 Performing a registry update allowed the authors to include a total of 7,119 recipients, with a split of 6,004 under the old system as compared to 1,115 under the new allocation system. 88 Recipients transplanted under the new system were more likely to be bridged to transplant with temporary MCS devices, have shorter waitlist times, and longer graft ischemic times. They were less likely to have durable left ventricular assist devices, diabetes, and ischemic cardiomyopathy. The comparison of donor characteristics were similar between the two cohorts, with the exception that in the old system the most likely cause of death was head trauma, while in the new system the most likely cause was anoxia. 88 Unadjusted Kaplan-Meier survival analysis performed by the authors established a minimal decrease in 90 and 180-day survival with 93.0% and 90.6%, respectively, under the new allocation system as compared with 94.4% and 93.3% under the old system. 88 However, after adjusted analysis was performed to determine 28 independent association between the new allocation system and survival, there was no significant decrease in survival between the old and new systems. Independently identified factors associated with decrease in survival included increasing donor and recipient age, pre-transplant extracorporeal membrane oxygenation utilization, previous cardiac surgery, and prolonged graft ischemic time. 88 The selected themes for the 2020 highlights article summarize diverse aspects and ongoing innovations within the specialty of cardiothoracic and vascular anesthesia. It is likely that these latest studies will not only advance the practice domains for our specialty but also improve outcomes for all patients seeking cardiothoracic and vascular surgical care. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to report. 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Used with permission from Haft et al Kaplan-Meier survival within 1 year of transplant by diagnosis (adult heart transplants NICM: non-ischemic cardiomyopathy; VCM: valvular cardiomyopathy CAD, coronary artery disease ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump; IV, intravenous; MCS, mechanical circulatory support; PAC, pulmonary artery catheter; RVAD, right ventricular access device; TAH, total artificial heart VAD, ventricular access device * Most common status 1A exception categories: VT/VF, no IV access for inotropes/PAC contraindicated, congenital, VAD complications, unable to tolerate inotropes, other/miscellaneous, retransplantation, other (hypertrophic cardiomyopathy, restrictive cardiomyopathy † Most common status 1B exception categories: VT/VF, congenital, retransplantation, CD refractory angina, restrictive cardiomyopathy, unable to tolerate inotropes, VAD complications Barbara Weisser, Mayo Clinic Academic Support Office, Scottsdale, Arizona, USA.