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Sedation Practice in Intensive Care Evaluation (SPICE-III) trial reported significant heterogeneity in mortality with dexmedetomidine treatment. Supplemental propofol was commonly used to achieve desirable sedation.to quantify the association of different infusion rates of dexmedetomidine or propofol, given in combination, with mortality and if this is modified by age.We included 1177 patients randomized in SPICE-III to receive dexmedetomidine and given supplemental propofol, stratified by age (65 or ≤65 years). We used double stratification analysis to produce quartiles of steady infusion rates of dexmedetomidine, while escalating propofol dose and vice versa. We used Cox proportional hazard and multivariable regression, adjusted for relevant clinical variable to evaluate the association of sedative dose with 90-day mortality.Younger patients 598/1177(50.8%) received a significantly higher dose of both sedatives compared with older patients, to achieve comparable sedation depth. On double stratification analysis, escalating infusion rates of propofol to 1.27 mg/kg/h at a steady dexmedetomidine infusion rate (0.54 mcg/kg/h) was associated with reduced adjusted mortality in younger, but not older patients. This was consistent with multivariable regression modelling [hazard ratio: 0.59(95% Confidence Interval 0.43-0.78),P0.0001], adjusted for baseline risk and interaction with dexmedetomidine dose. In contrast, among younger patients using multivariable regression, escalating dexmedetomidine infusion rate was associated with increased adjusted mortality [HR:1.30(95%CI 1.03-1.65), P=0.029].In patients ≤ 65 years sedated with dexmedetomidine and propofol combination, preferentially increasing the dose of propofol was associated with decreased adjusted 90-day mortality. Conversely, increasing dexmedetomidine may be associated with increased mortality. Clinical trial registration available at www.gov, ID: NCT01728558.

Frank Knight's theory of monopoly price has received relatively little attention in the literature on Risk, Uncertainty and Profit. We argue that Knight accepted and refined the monopoly price theory of Carl Menger and his followers. Knight highlights the difference between monopoly as an inevitable outcome of departures from perfect competition, and monopoly as a contingent or ‘culture-history fact’. In the latter case, coercive institutional barriers to potential competition shape the choice set of consumers and producers, and provide a crucial method for identifying monopoly gains. There are three benefits to this account of Knight's contributions: it rehabilitates the focus on the institutional determinants of monopoly price, as opposed to the mainstream emphasis on market frictions and imperfections; it opens the way for a Mengerian monopoly price theory that seriously engages the study of institutions; and it adds new evidence and nuance to ongoing debates about Knight's place in economics.

Should economics be pursued as a profession or a vocation? Below I argue that this choice of subjective orientation is enormously important, and tends to dictate whether an economist will serve the cause of truth and freedom, or waste his or her talents on convenience, ephemera, and statism. The New Shorter Oxford English Dictionary gives one definition of «vocation» as «The work or function to which a person is called; a mode of life or employment regarded as requiring dedication». The eminent semanticist S.I. Hayakawa also emphasizes «dedication» as the distinctive feature of a vocation which differentiates it from a profession. In praxeological terms, a vocation involves what Ludwig von Mises «introversive» labor while a profession involves «extroversive» labor. The essence of introversive labor is work undertaken solely for its own sake and not as a means to a more remote end. Extroversive labor, in contrast, is performed because the individual «prefers the proceeds he can earn by working to the disutility of labor and the pleasure of leisure». One of the «two most conspicuous examples» of introversive labor, according to Mises, is «the search for truth and knowledge pursued for its own sake and not as a means of improving one’s own efficiency and skill in the performance of other kinds of labor aiming at other ends». The second is «genuine sport, practiced without any design for reward and social success». It is not that the effort expended by the «truth seeker» or «mountain climber» does not involve the disutility of labor, rather «it is precisely overcoming the disutility of labor that satisfies him». Thus genuine truth seeking in any scientific discipline qualifies economically as «consumption» and its pursuit as a vocation.

The centennial of the publication of the first German edition of Ludwig von Mises’s The Theory of Money and Credit offers an excellent opportunity to reconsider a long-standing controversy within modern Austrian economics. This revolves around the question of whether Ludwig von Mises favored 100-percent gold reserve banking imposed by law or free banking based on gold as the ideal monetary system. In this paper, I suggest that this debate is fundamentally misfocused and conflates means and ends. I argue that Mises advocated free banking as the most suitable means for achieving the goal of suppressing the issue of fiduciary media, in the form of bank notes and demand deposits. This goal was first enunciated by the nineteenth-century British currency school and embodied in its famous «currency principle.» My thesis is that Mises was a proponent of both the currency principle and free banking and that he viewed the latter as the indispensable means to regulate the behavior of the money supply according to the former. In defending this thesis, I seek to reframe the debate on Mises’s monetary views in a more meaningful way and to contribute to its resolution. Key words: Mises, Currency School, Free Banking, Currency Principle, Monetary Equilibrium. JEL Classification: B31, B53, E42, E52. Resumen: El centenario de la publicación de la primera edición alemana de The Theory of Money and Credit de Ludwig von Mises, ofrece una exce-lente oportunidad para reconsiderar una controversia duradera dentro de la economía austriaca moderna. Ésta gira en torno a la cuestión de si Ludwig von Mises apoyó una banca de reserva en oro del 100% impues-ta por ley o una banca libre basada en el oro como su sistema monetario ideal. En este trabajo, sugiero que este debate está fundamentalmente mal enfocado y confunde medios y fines. Sostengo que Mises defendió un siste-ma de banca libre como el medio más adecuado para lograr el objetivo de suprimir la emisión de dinero fiduciario en forma de billetes bancarios y depósitos a la vista. Este objetivo fue inicialmente enunciado por la Escue-la Monetaria del siglo XIX e incorporado en su famoso «principio mone-tario.» Mi tesis es que Mises fue proponente del principio monetario y de la banca libre, y que observó a esta última como el medio indispensable para regular el comportamiento de la oferta monetaria conforme al prime-ro. En la defensa de esta tesis, trato de replantear el debate sobre las ideas monetarias de Mises de una forma más relevante y contribuir de este modo a su resolución. Palabras clave: Mises, Escuela Monetaria, Banca Libre, Principio Monetario, Equilibrio Monetario. Clasificación JEL: B31, B53, E42, E52.

A 55-year-old patient was found to have complete heart block during preoperative assessment. Cardiac magnetic resonance imaging revealed an interatrial mass suggestive of primary cardiac tumor. Extensive evaluation including intracardiac biopsy and finally open resection revealed lipomatous hypertrophy masquerading as tumor. (Level of Difficulty: Intermediate.), Graphical abstract

Fegley and Israel (2020) have advanced the thesis that the status of leisure as a consumer good is an immediate inference from the action axiom rather than an empirical postulate as maintained by Mises and Rothbard. This comment argues that we can easily imagine a world in which leisure does not represent the opportunity cost of labor, and that Mises and Rothbard have been misconstrued. Additionally, I am strongly unsympathetic to the mode of argument they use in making their case, which is to directly challenge well-established foundational concepts and relations of economic theory. This may only provoke arid quibbling over epistemology.

Karl-Friedrich Israel (2018) sees “obvious tension” in a book chapter (Salerno 2018) in which I argue that the Hicksian income effect plays no role in the causal-realist approach to the demand curve. Israel’s reconstructed “wealth effect” is an effort to solve this perceived problem. This comment addresses the expositional gap in my analysis, and resolves the perceived tension. I then outline the problems with Israel’s proposed solution, which involves a wholesale reconstruction of demand theory that, in the end, implies a denial of the law of demand.

Outcomes in patients with smaller body size after HeartMate 3 left ventricular assist device (HM3) implantation are not well characterized. We sought to evaluate outcomes in smaller vs larger body surface area (BSA) patients in the MOMENTUM 3 pivotal trial and its Continued Access Protocol cohort.The analysis cohort included 1015 HM3 patients divided into 2 groups: BSA ≤1.70 mSmaller patients were more frequently women (56.1% vs 17.7%; P.001) and had lower prevalence of diabetes (28.1% vs 43.9%; P = .005) and hypertension (51.2% vs 71.9%; P.001), larger median indexed LVEDD (normalized by BSA, 40 vs 33 mm/mOutcomes after HM3 implantation were comparable between small and large patients. Smaller body size should not be used to deny HM3 implantation in patients who are otherwise suitable candidates for durable mechanical circulatory support.

The HeartWare HVAD System (Medtronic) is a durable implantable left ventricular assist device that has been implanted in approximately 20,000 patients worldwide for bridge to transplant and destination therapy indications. In December 2020, Medtronic issued an Urgent Medical Device Communication informing clinicians of a critical device malfunction in which the HVAD may experience a delay or failure to restart after elective or accidental discontinuation of pump operation. Moreover, evolving retrospective comparative effectiveness studies of patients supported with the HVAD demonstrated a significantly higher risk of stroke and all-cause mortality when compared with a newer generation of a commercially available durable left ventricular assist device. Considering the totality of this new information on HVAD performance and the availability of an alternate commercially available device, Medtronic halted the sale and distribution of the HVAD System in June 2021. The decision to remove the HVAD from commercial distribution now requires the use of the HeartMate 3 left ventricular assist system (Abbott, Inc) if a patient previously implanted with an HVAD requires a pump exchange. The goal of this document is to review important differences in the design of the HVAD and HeartMate 3 that are relevant to the medical management of patients supported with these devices, and to assess the technical aspects of an HVAD-to-HeartMate 3 exchange. This document provides the best available evidence that supports best practices. (J Thorac Cardiovasc Surg 2022;-:1-8).

What is now called the judgment-based approach to entrepreneurship (JBA) has a rich pedigree in Austrian economics and continues to grow rapidly in that tradition as well as in various research fields in business and management. The JBA has also attracted some criticisms. Frédéric Sautet’s recent review essay is an example. Sautet’s main concern is that the JBA rejects Israel Kirzner’s alertness/discovery approach which, in Sautet’s view, provides a more compelling basis for theorizing. Unfortunately, we do not find Sautet’s criticisms of the JBA convincing. They frequently ignore our arguments about entrepreneurial judgment and its manifestation in the business firm, fail to address our criticisms of the alertness/discovery approach, and are rooted in a flawed understanding of the history of economic thought.

Shared decision making with patients in advanced heart failure is critical when making decisions on therapies such as left ventricular assist device implantation and cardiac transplantation. We describe a case wherein the risks of coronavirus disease-2019 affected the decision of a patient regarding proceeding with cardiac transplantation. (Level of Difficulty: Beginner.).

In two interim analyses of this trial, patients with advanced heart failure who were treated with a fully magnetically levitated centrifugal-flow left ventricular assist device were less likely to have pump thrombosis or nondisabling stroke than were patients treated with a mechanical-bearing axial-flow left ventricular assist device.We randomly assigned patients with advanced heart failure to receive either the centrifugal-flow pump or the axial-flow pump irrespective of the intended goal of use (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or remove a malfunctioning device. The principal secondary end point was pump replacement at 2 years.This final analysis included 1028 enrolled patients: 516 in the centrifugal-flow pump group and 512 in the axial-flow pump group. In the analysis of the primary end point, 397 patients (76.9%) in the centrifugal-flow pump group, as compared with 332 (64.8%) in the axial-flow pump group, remained alive and free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years (relative risk, 0.84; 95% confidence interval [CI], 0.78 to 0.91; P0.001 for superiority). Pump replacement was less common in the centrifugal-flow pump group than in the axial-flow pump group (12 patients [2.3%] vs. 57 patients [11.3%]; relative risk, 0.21; 95% CI, 0.11 to 0.38; P0.001). The numbers of events per patient-year for stroke of any severity, major bleeding, and gastrointestinal hemorrhage were lower in the centrifugal-flow pump group than in the axial-flow pump group.Among patients with advanced heart failure, a fully magnetically levitated centrifugal-flow left ventricular assist device was associated with less frequent need for pump replacement than an axial-flow device and was superior with respect to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755.).

Background: The MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) has demonstrated that the HeartMate 3 (HM3) pump is associated with reduced strokes compared with the HeartMate II (HMII) device. We now perform a comprehensive analysis of stroke events to evaluate their longitudinal occurrence, clinical correlates, patterns, and impact on outcome across the 2-year duration of support. Methods: MOMENTUM 3 is a randomized controlled trial of the HM3 centrifugal-flow pump versus the HMII axial-flow pump in patients with advanced heart failure, regardless of the intended goal of support (bridge to transplantation or destination therapy). Baseline and postimplantation clinical correlates of stroke events were assessed with multivariable analyses. Longitudinal patterns, including device association, type of stroke (hemorrhagic versus ischemic), changing severity of impairment assessed with the modified Rankin Scale (disabling [modified Rankin Scale score >3] versus nondisabling [modified Rankin Scale score ≤3]) over time, and association with outcome, were determined. Results: In 361 patients with the intended implant (189 HM3 and 172 HMII), 65 strokes (40 ischemic strokes and 25 hemorrhagic strokes) occurred in 52 patients at a median of 131 (range, 1–733) days. No difference in stroke rate was noted between 0 and 180 days of follow-up between devices. However, stroke incidence in the long-term period (181–730 days after left ventricular assist device) was 3.3 times lower for the HM3 group (HM3: 0.04 versus HMII: 0.13 events per patient-year; odds ratio, 0.23; 95% CI, 0.08–0.63; P =0.01). Treatment with the HM3 pump was the only independent predictor of lower stroke events. We found no direct association of blood pressure or antithrombotic regimens with observed stroke rates. A stroke event significantly lowered 2-year postimplantation survival regardless of subtype or initial severity of neurological impairment compared with patients without a stroke (43±12% for hemorrhagic stroke, 57±9% for ischemic stroke, 51±11% for disabling, and 51±11% for nondisabling compared with 85±2% 2-year survival for patients without stroke). Conclusions: The HM3 pump is associated with a marked reduction in stroke rates compared with the HMII device, with benefits observed in the long-term period (>6 months). The occurrence of stroke of any type (hemorrhagic and ischemic) or of any functional severity (disabling and nondisabling) is predictive of a poor 2-year clinical outcome. Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02224755.

Left ventricular assist devices (LVAD) have been increasingly used in the treatment of end-stage heart failure. While warfarin has been uniformly recommended in the long-term as anticoagulation strategy, no clear recommendation exists for the post-operative period. We sought to evaluate the feasibility of enoxaparin in the immediate and early postoperative period after LVAD implantation.This is a two-center, retrospective analysis of 250 consecutive patients undergoing LVAD implantation between January 2017 and December 2018. Patients were bridged postoperatively to therapeutic INR by either receiving unfractionated heparin (UFH) or low molecular weight heparin (LMWH). Patients were followed while inpatient and for 3 months after LVAD implantation. The efficacy outcome was occurrence of first and subsequent cerebrovascular accident while safety outcome was the occurrence of bleeding events. Length of stay (LOS) was also assessed.Two hundred fifty and 246 patients were analyzed for index admission and 3-month follow up respectively. No statistically significant differences were found between the two groups in CVA (OR = 0.67; CI = 0.07-6.39, P = 0.73) or bleeding events (OR = 0.91; CI = 0.27-3.04, P = 0.88) during index admission. Similarly, there were no differences at 3 months in either CVAs or bleeding events (OR = 0.85; 0.31-2.34; p = 0.76). No fatal events occurred during the study follow-up period. Median LOS was significantly lower (4 days; p = 0.03) in the LMWH group.LMWH in the immediate and early postoperative period after LVAD implantation appears to be a concurrently safe and efficacious option allowing earlier postoperative discharge and avoidance of recurrent hospitalizations due to sub-therapeutic INR.

Objective To determine characteristics, outcomes, and clinical factors associated with death in patients with COVID-19 requiring extracorporeal membrane oxygenation (ECMO) support. Methods A multicenter, retrospective cohort study was conducted. The cohort consisted of adult patients (18 years of age and older) requiring ECMO in the period from March 1, 2020, to September 30, 2020. The primary outcome was in-hospital mortality after ECMO initiation assessed with a time to event analysis at 90 days. Multivariable Cox proportional regression was used to determine factors associated with in-hospital mortality. Results Overall, 292 patients from 17 centers comprised the study cohort. Patients were 49 (interquartile range, 39-57) years old and 81 (28%) were female. At the end of the follow-up period, 19 (6%) patients were still receiving ECMO, 25 (9%) were discontinued from ECMO but remained hospitalized, 135 (46%) were discharged or transferred alive, and 113 (39%) died during the hospitalization. The cumulative in-hospital mortality at 90 days was 42% (95% confidence interval [CI], 36%-47%). Factors associated with in-hospital mortality were age (adjusted hazard ratio [aHR], 1.31; 95% CI, 1.06-1.61 per 10 years), renal dysfunction measured according to serum creatinine level (aHR, 1.21; 95% CI, 1.01-1.45), and cardiopulmonary resuscitation before ECMO placement (aHR, 1.87; 95% CI, 1.01-3.46). Conclusions In patients with severe COVID-19 necessitating ECMO support, in-hospital mortality occurred in fewer than half of the cases. ECMO might serve as a viable modality for terminally ill patients with refractory COVID-19., Graphical abstract A multicenter, retrospective cohort study of 292 patients with COVID-19 given extracorporeal membrane oxygenation (ECMO) in 17 centers across the United States from March 1, 2020 to September 30, 2020. Clinical characteristics and outcomes were entered into a Research Electronic Data Capture (REDCap) database. The primary outcome of cumulative in-hospital mortality at 90 days was 42% (95% confidence interval [CI], 36%-47%).

Background Left ventricular assist devices (LVAD) have been increasingly used in the treatment of end-stage heart failure. While warfarin has been uniformly recommended in the long-term as anticoagulation strategy, no clear recommendation exists for the post-operative period. We sought to evaluate the feasibility of enoxaparin in the immediate and early postoperative period after LVAD implantation. Methods This is a two-center, retrospective analysis of 250 consecutive patients undergoing LVAD implantation between January 2017 and December 2018. Patients were bridged postoperatively to therapeutic INR by either receiving unfractionated heparin (UFH) or low molecular weight heparin (LMWH). Patients were followed while inpatient and for 3 months after LVAD implantation. The efficacy outcome was occurrence of first and subsequent cerebrovascular accident while safety outcome was the occurrence of bleeding events. Length of stay (LOS) was also assessed. Results Two hundred fifty and 246 patients were analyzed for index admission and 3-month follow up respectively. No statistically significant differences were found between the two groups in CVA (OR = 0.67; CI = 0.07–6.39, P = 0.73) or bleeding events (OR = 0.91; CI = 0.27–3.04, P = 0.88) during index admission. Similarly, there were no differences at 3 months in either CVAs or bleeding events (OR = 0.85; 0.31–2.34; p = 0.76). No fatal events occurred during the study follow-up period. Median LOS was significantly lower (4 days; p = 0.03) in the LMWH group. Conclusions LMWH in the immediate and early postoperative period after LVAD implantation appears to be a concurrently safe and efficacious option allowing earlier postoperative discharge and avoidance of recurrent hospitalizations due to sub-therapeutic INR.

Neutral money plays a central role in contemporary macroeconomic theory, and is a live issue in recent monetary policy discussions. We challenge the opinion that Hayek’s writings on neutral money have been influenced by, and are similar to, the work of Menger and Mises. We show, first, the significant alternative influence of Friedrich von Wieser on Hayek’s work on the subject. Second, we rehabilitate a neglected method of monetary theorizing specific to Menger and Mises that rejects money neutrality both as a tool for investigating monetary phenomena and as the standard by which monetary regimes, and the market economy itself, should be evaluated. Examining this chapter in the history of economic thought can aid in a deeper reconsideration of the doctrinal foundations of modern monetary theory and policy.

Highly specialized left ventricular assist device care is not readily available in many areas, potentially limiting access to therapy. This retrospective analysis examines the relationship of outcomes by patient distance from implanting left ventricular assist device center within the Mechanical Circulatory Support Research Network. Zip codes were used to calculate patient distance, with the primary outcome of interest being 3-year survival by distance from the surgical center. Secondary outcomes included 90-day survival and incident event rates for the following: gastrointestinal bleeding, infection, cerebral event, and pump thrombosis. Across the four centers, there were 1184 patients supported for a median of 486 days. Overall survival was 91 ± 0.8% at 90 days and 61 ± 1.9% at 3 years, with worse 3-year survival in those living >90 vs. ≤90 miles from the ventricular assist device implant center (55 ± 3.0% vs. 64 ± 2.5, p = 0.019). Patients living >90 miles from an implant center were older, more likely to be implanted for destination therapy support, had a prior sternotomy, and had worse renal function than those living closer (p

Background: The MOMENTUM 3 trial compares the centrifugal HeartMate 3 (HM3) with the axial HeartMate II (HMII) continuous-flow left ventricular assist system in patients with advanced heart failure, irrespective of the intended goal of therapy. The trial’s 2-year clinical outcome (n=366) demonstrated superiority of the HM3 for the primary end point (survival free of a disabling stroke or reoperation to replace or remove a malfunctioning pump). This analysis evaluates health resource use and cost implications of the observed differences between the 2 devices while patients were enrolled in the trial. Methods: We analyzed all hospitalizations and their associated costs occurring after discharge from the implant hospitalization until censoring (study withdrawal, heart transplantation, and pump exchange with a nonstudy device or death). Each adjudicated episode of hospital-based care was used to calculate costs (device-attributable and non–device-attributable event costs), estimated by using trial data and payer administrative claims databases. Cost savings stratified by subgroups (study outcome [transplant, death, or ongoing on device], intended goal of therapy, type of insurance, or sex) were also assessed. Results: In 366 randomly assigned patients, 361 comprised the as-treated group (189 in the HM3 group and 172 in the HMII group), of whom 337 (177 in the HM3 group and 160 in the HMII group) were successfully discharged following implantation. The HM3 arm experienced fewer total hospitalizations per patient-year (HM3: 2.1±0.2 versus HMII: 2.7±0.2; P =0.015) and 8.3 fewer hospital days per patient-year on average (HM3: 17.1 days versus HMII: 25.5 days; P =0.003). These differences were driven by patients hospitalized for suspected pump thrombosis (HM3: 0.6% versus HMII: 12.5%; P P =0.002). Controlled for time spent in the study (average cumulative cost per patient-year), postdischarge HM3 arm costs were 51% lower than with the HMII (HM3: $37 685±4251 versus HMII: $76 599±11 889, P Conclusions: In this 2-year outcome economic analysis of the MOMENTUM 3 trial, the HM3 demonstrated a reduction in rehospitalizations, hospital days spent during rehospitalizations, and a significant cost savings following discharge in comparison with the HMII left ventricular assist system, irrespective of the intended goal of therapy. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02224755.

Background Primary outcomes analysis of the Multicenter Study of MagLev Technology in Patients Undergoing MCS Therapy With HeartMate 3 (MOMENTUM 3) trial short-term cohort demonstrated a higher survival rate free of debilitating stroke and reoperation to replace/remove the device (primary end-point) in patients receiving the HeartMate 3 (HM3) compared with the HeartMate (HMII). In this study we sought to evaluate the individual and interactive effects of pre-specified patient subgroups (age, sex, race, therapeutic intent [bridge to transplant/bridge to candidacy/destination therapy] and severity of illness) on primary end-point outcomes in MOMENTUM 3 patients implanted with HM3 and HMII devices. Methods Cox proportional hazard models were used to analyze patients enrolled in the “as-treated cohort” ( n = 289) of the MOMENTUM 3 trial to: (1) determine interaction of various subgroups on primary end-point outcomes; and (2) identify independent variables associated with primary end-point success. Results Baseline characteristics were well balanced among HM3 ( n = 151) and HMII ( n = 138) cohorts. No significant interaction between the sub-groups on primary end-point outcomes was observed. Cox multivariable modeling identified age (≤65 years vs >65 years, hazard ratio 0.42 [95% confidence interval 0.22 to 0.78], p = 0.006]) and pump type (HM3 vs HMII, hazard ratio 0.53 [95% confidence interval 0.30 to 0.96], p = 0.034) to be independent predictors of primary outcomes success. After adjusting for age, no significant impact of sex, race, therapeutic intent and INTERMACS profiles on primary outcomes were observed. Conclusions This analysis of MOMENTUM 3 suggests that younger age (≤65 years) at implant and pump choice are associated with a greater likelihood of primary end-point success. These findings further suggest that characterization of therapeutic intent into discrete bridge-to-transplant and destination therapy categories offers no clear clinical advantage, and should ideally be abandoned.

Purpose Left ventricular assist device (LVAD) explant or decommission for LV recovery is rare (1-2%). Furthermore, details regarding appropriate patient selection, surgical technique and short- and long-term patient outcomes are limited (1,2). Four different surgical techniques have been described for cessation of LVAD support for LV recovery (3). The purpose of our study is to describe our experience for patients undergoing LVAD explantation or decommission. Methods We retrospectively reviewed the surgical technique and outcomes for our LVAD patients who were explanted and decommissioned between 2010 and 2020. Baseline demographics were examined. Specific surgical techniques utilized along with outcome analysis including infection, thromboembolic events, LVEF change, need for re-implantation and death were analyzed. Results Thirteen patients were identified who underwent either LVAD explant or decommission with a mean age of 43. All patients had underlying non-ischemic cardiomyopathy. Nearly half (53%) of the patients were selected due to a combination of LV recovery (mean LVEF 47% in this group) and an indication for device removal including pump thrombosis or infection (versus LV recovery alone). Surgical technique varied between full sternotomy with pump explant (69%) and thoracotomy with pump decommission (31%) depending on indication. Median follow up was 70 months. Results are displayed in table 1. In those with LV recovery alone, many experienced a drop in LVEF with clinical HF symptoms, but not resulting in re-implantation or mortality. All patients with infection and LV recovery experienced a drop in LVEF and recurrent HF, with a mortality rate of 50%. Conclusion LVAD explant or decomissioning can be performed via full sternotomy or thoracotomy depending on the indication. When performed for LV recovery and another reason, such as device infection, recurrent, severe HF can be fatal in this cohort. Careful monitoring of these patients is therefore required after such an operation.

Device indications have changed for placement of continuous-flow left ventricular assist devices (CF-LVADs). We performed a multicenter analysis evaluating temporal variations in outcomes after CF-LVAD implantation.We retrospectively defined 3 time intervals to reflect changes in CF-LVAD technology (period 1, 2004-2009; period 2, 2010-2012; and period 3, 2012-2014). A total of 1,064 patients (Heartmate II [HMII] = 835; Heartware [HVAD] = 229) underwent CF-LVAD implantation from May 2004 to October 2014. Device utilization was different between periods: period 1: HMII = 134 (100%); period 2: HMII = 480 (88%) and HW = 63 (12%); and period 3: HMII = 221 (57%) and HW = 166 (43%); P .001. Despite few baseline group differences, adjusted survivals were similar among the time periods (P = .96). Adjusted multivariable analysis revealed age (per 10-year increase) and Interagency Registry for Mechanically Assisted Circulatory Support category (1 vs all others) as the only independent predictors of mortality: P .001 and P = .008, respectively. Furthermore, it also showed the later periods to be at an increased risk of adverse events: 1) pump thrombosis (periods 2 and 3); and 2) gastrointestinal bleeding (period 3).Despite significant differences in device types, indications, and patient characteristics, post-implantation survivals were similar across time intervals. The most recent cohort seems to be at an increased risk of gastrointestinal bleeding and pump thrombosis.

Temporary circulatory support (TCS) is used to stabilize patients in critical cardiogenic shock and bridge patients to a durable ventricular assist device (VAD). Whether TCS confers increased risk at the time of VAD implant is unknown.Prospectively collected data from five institutions was retrospectively reviewed. All profile 1 through profile 3 patients implanted with a continuous-flow VAD (n = 804) were categorized into three groups: TCS (n = 68); non-TCS profile 1 (n = 70); and non-TCS profile 2-3 (n = 666).End-organ function and hemodynamics were worse before TCS than in non-TCS profile 1 patients: creatinine (1.7 ± 0.1 mg/dL versus 1.3 ± 0.06 mg/dL, p = 0.003); and right atrial pressure (16 ± 0.8 mm Hg versus 13 ± 1.1 mm Hg, p = 0.048). The TCS restored cardiac output before durable VAD (4.9 ± 0.2 L/min), and was comparable to profile 2-3 patients (4.3 ± 0.05 L/min) and better than profile 1 patients (4.0 ± 0.2 L/min, p = 0.002). Markers of hepatic function such as bilirubin were impaired before VAD in TCS and profile 1 patients (2.0 ± 0.2 mg/dL) compared with profile 2 and 3 patients (1.1 ± 0.03, p0.001). The incidence of postoperative right ventricular failure necessitating a right VAD was 21% for TCS patients and non-TCS profile 1 patients compared with 2% for profile 2-3 patients (p0.001). Profile 1 and TCS patients had similar 1-year survival (70% and 77%, p = 0.57), but inferior survival as compared with profile 2 and 3 patients (82%, p0.001). On multivariable analysis, TCS increased the hazard of death twofold.Temporary circulatory support restores hemodynamics and reverses end-organ dysfunction. Nevertheless, these patients have high residual risk with postoperative morbidity and mortality that parallels profile 1 patients without TCS. Caution is suggested in downgrading risk for TCS patients with improved hemodynamic stability.

Introduction Cardiac transplant centers are now successfully utilizing hepatitis C virus (HCV) donor hearts to increase the availability of organs now that a curative treatment is available with direct acting antivirals (DAA). We present the first described case of DAA treatment failure in a patient who received an HCV donor, nucleic acid testing (NAT) positive heart. Case Report A 65-year-old male with a mixed cardiomyopathy underwent orthotopic heart transplant with an HCV+/NAT+ heart. He seroconverted within seven days of transplant, noted by a peak HCV viral load of 7.65 log IU/mL and genotype of 1a without resistance markers. Planned initial treatment with glecaprevir/pibrentasvir (G/P) was denied by insurance. After approval for and treatment with ledipasvir/sofosbuvir (L/S) for 8 weeks, the patient's viral load was initially undetectable. However, he developed recurrent viremia 6 months after treatment completion with an HCV load of 7.40 log IU/mL with NS5A resistance due to a Y93H mutation. He was subsequently initiated on sofosbuvir/velpatasvir/voxilaprevir (S/V/V) with persistent undetectable viral loads to date at 4 months. Summary This is the first documented case of DAA treatment failure in a recipient of HCV+/NAT+ transplanted heart treated with L/S. This treatment failure was likely secondary to insufficient treatment duration. The ION-3 study demonstrated noninferiority for an 8 week treatment duration compared to 12 weeks of L/S, but at the cost of a higher relapse rate in the 8 week arm (5% vs 1%) associated with viral load of >6.78 log IU/mL. The Y93H mutation is more likely to reduce treatment efficacy in L/S as noted by a pooled resistance analysis compared to G/P, which has a failure rate of

The field of mechanical circulatory support has been impacted by the approval of new continuous-flow left ventricular assist devices (LVADs) and changes to the United States heart allocation system.Primary isolated continuous-flow LVAD implants in The Society of Thoracic Surgeons Intermacs registry from January 2014 through September 2019 were evaluated. Survival and freedom from major adverse events were compared between axial-flow, centrifugal-flow with hybrid levitation (CF-HL), and centrifugal-flow with full magnetic levitation (CF-FML) devices.Of 2603 devices implanted in 2014, 1824 (70.1%) were axial flow and 1213 (46.6%) were destination therapy (DT); through September 2019, 1752 devices were implanted, but only 37 (2.1%) were axial flow and 1230 (70.2%) were DT. Implants were performed in 13,016 patients between 2014 and 2018. Patients receiving implants in 2017-2018 compared with 2014-2016 were more likely to be at Intermacs profile 1 (17.1% vs 14.3%, P.001) and to have preimplant temporary mechanical circulatory support (34.8% vs 29.3%, P.001). Overall survival and freedom from major adverse events were higher with CF-FML devices. In multivariable analysis of survival between CF-HL and CF-FML, device type was not a significant early hazard, but the use of CF-HL devices had a late hazard ratio for death of 3.01 (P .001).Over the past 5 years, centrifugal-flow LVADs have become the dominant technology and DT the most common implant strategy. While outcomes with CF-FML devices are promising, comparisons with other devices from nonrandomized registry studies should be made with caution.

Introduction Patients with end-stage heart failure eligible for orthotopic heart transplantation (OHT) exceed the number of available donor organs. With highly effective hepatitis C virus (HCV) antiviral therapy now available, HCV+ organs are increasingly utilized. We seek to describe our experience with patients receiving HCV viremic organs as compared to non-HCV transplant recipients. Methods Our center began utilizing HCV hearts in February 2018. We retrospectively reviewed baseline demographics, laboratory data and outcomes for those undergoing OHT with majority being from a viremic HCV donor. Results Twenty-three of 25 HCV recipients received hearts from NAT+ donors with 22 of 23 seroconverting within 7 days. Fifteen recipients have completed HCV treatment, with the longest duration of follow-up being 13 months. No differences in rates of rejection, hospitalizations or death were seen between non-HCV and HCV transplant patients. Discussion With the advent of available direct-acting antivirals (DAAs), viremic HCV hearts provide an opportunity to increase organ availability. Moreover, treatment for HCV in the setting of immunosuppression is well-tolerated and results in sustained viremic response. Conclusion Viremic, discordant HCV OHT can be performed in a safe and effective manner utilizing a systematic, multidisciplinary approach without an effect on short-term outcomes.

Left ventricular assist device (LVAD) therapy remains a vital therapeutic option for patients with end-stage heart failure. Unfortunately, adverse events can occur and progress to require consideration for device exchange once the failure of medical management becomes evident, especially when heart transplantation is not possible in a timely manner. The aim of this analysis is to describe the incidence and outcomes of LVAD exchanges at our institution. Between April 2008 and May 2017, 397 patients underwent LVAD implantation, with 32 of those patients subsequently receiving exchange upon the recommendation of our multidisciplinary team due to refractory infection (n=12), device malfunction (n=5), hemolysis (n=9) and pump thrombosis (n=6). The average time from index implant to exchange was 580.6 days, with an average length of stay of 18.2 days. Survival at 3 months was 84.4%, 75.0% at 1 year and median at 8.3 years after exchange. The most common adverse events, occurring in less than 1/3 of the population, included bleeding, infection and stroke. This study suggests that LVAD exchange can be an effective and definitive mechanism for the treatment of otherwise potential fatal pump complications in highly select patients. Copyright: © 2019The Author(s). This is an open access article published under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License(https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided that the original author(s) and the publication source are credited.

Purpose In October 2018, the United Network for Organ Sharing (UNOS) implemented extensive changes to the adult heart allocation policy. These changes were developed to better stratify medically urgent patients and provide more equitable geographic distribution of donor hearts. Instead of preferential distribution within a local donor service area, hearts are first considered by centers within 500 nautical miles of a donor hospital. We evaluated the impact of the new system on the mode and associated expense of procurement travel. Methods We retrospectively analyzed data from 5 centers across 5 states and 4 UNOS regions (regions 2, 5, 10, 11). Pre-allocation change (pre-change) was considered 10/1/2016-10/17/2018 and post-allocation change (post-change) was considered 10/18/18-8/31/2019. The share of procurements requiring a flight vs local transportation from all centers was compared. Cost of transportation for procurement and distance from donor hospital to transplant center was available from 4 centers. Results Total of 693 transplants were performed during the study period: 477 pre-change and 216 post-change. Pre-change, there were 274 flights for procurement compared to 182 flights post-change (57 vs 84%, p Conclusion Following the 2018 UNOS change to the heart allocation system, the proportion of flights and distance traveled for organ procurements significantly increased across 5 moderate-high volume centers, nearly doubling the average travel cost for procurement. These findings may guide transplant centers, payers, and policy makers regarding necessary procurement resources. Further study is needed to determine how these changes may affect lower volume centers with fewer resources.

Purpose Hepatitis C (HCV) organs have been increasingly utilized in solid organ transplantation since the advent of curative direct acting anti-viral (DAA) therapy. Despite the adoption of this strategy, many unanswered questions remain regarding the management of immunosuppression. In two small case series of liver transplant recipients, tacrolimus concentrations have been shown to decrease with clearance of HCV viremia. We seek to describe our experience and clinical implications in our cardiac transplant population. Methods We adopted the strategy of HCV cardiac transplantation followed by curative treatment in February of 2018. We analyzed the change in tacrolimus levels after DAA therapy in those who developed viremic HCV after receiving an HCV organ. Immunosuppression regimens were not altered for these patients from standard of care, which includes no induction therapy, corticosteroid taper by 6 months, and tacrolimus and mycophenolate mofetil as tolerated. Drug levels of tacrolimus were collected, as were clinical outcomes inclusive of infection, rejection and death. Results Twenty of twenty six NAT+/HCV+ patients experienced a decrease in tacrolimus levels with treatment, from a mean of 11.6 to a mean of 6.5 after HCV treatment. This decrease occurred towards the end of treatment and did not correspond with changes in tacrolimus dosing or other immunosuppressive agents. When compared to the non-HCV transplant population (n=37), no change in outcomes were observed. Conclusion Treatment of HCV after transplantation may be correlated with increased metabolism, resulting in more rapid clearance of tacrolimus. Careful monitoring of drug levels and graft function is recommended as HCV organs are increasingly utilized. Further investigation into the clinical implications of these metabolic changes is warranted.

Objectives Secondary mitral regurgitation (MR), not amenable to percutaneous or surgical repair, is common in advanced heart failure patients considered for LVAD implantation. Single center analyses have suggested variable frequency of persistent MR after LVAD implantation and consequent pulmonary hypertension, worse right heart function and more readmissions. The contemporary impact of newer devices such as the HeartMate 3 (HM3) on amelioration of MR post-LVAD implant remains uncertain. In this analysis of the MOMENTUM 3 pivotal trial and its Continued Access Protocol (CAP) study, we propose to assess the burden of significant residual MR and to evaluate the impact on clinical outcomes. Methods Patients implanted with the HeartMate II (HMII) or HM3 pump in the MOMENTUM 3 pivotal trial were evaluated over 24 months to assess their relative impact on residual MR. An extended analysis of the first 500 implanted patients in CAP (HM3 only) will also be performed to validate observations from within the pivotal trial. Data on the presence and severity of MR using echocardiography were collected at baseline (pre-implant) and throughout the 24-month follow-up. Endpoints In the pivotal trial (n=1020), 44% of patients had significant (moderate to severe) MR at baseline and 8.8% (90/1020) had undergone a prior or concomitant mitral valve procedure. In patients with no surgical mitral valve correction, overall rates of significant residual MR (irrespective of baseline MR) at each follow-up visit are shown in Figure 1. Of those patients with significant MR at baseline, 28% had persistent significant residual MR during study follow-up. In this group, HM3 patients experienced a lower frequency of significant residual MR (24%) than HMII patients (33%, p=0.05). Survival, right heart failure, and freedom from all-cause readmissions were not significantly different between patients with and without significant residual MR. Endpoints will also be validated in the CAP cohort and in patients with concomitant mitral valve correction. (Funded by Abbott).

Purpose In the era of increased left ventricular support device (LVAD) implantation, limited data is available on outcomes in the obese population, with most available data describing elevated BMI with a cutoff of >30 kg/m2. Forest et al examined the ISHLT Mechanically Assisted Circulatory Support (IMACS) registry and found no impact in 2-year mortality in those with higher BMIs, but an increase in all adverse events describing BMI > 40 kg/m2 group. We seek to provide our experience with this population. Methods We retrospectively reviewed outcomes in over 580 LVAD implantations performed at St. Vincent, Indianapolis IN between 2008-19. Baseline demographics of BMI subgroups (BMI 40 kg/m2) and outcomes were collected. Endpoints including survival, stroke, infection, gastrointestinal (GI) bleeding and right heart failure (RHF) were analyzed by BMI strata, with a specific focus on BMI > 40 kg/m2. RHF was defined with Interagency for Mechanically Assisted Circulatory Support (INTERMACS) definitions. Results Over 8% of LVAD patients had a BMI > 40 kg/m2 in our population. No differences were found in survival, stroke, infection, GI bleeding or hemolysis. Figure 1 displays time to right heart failure in BMI subgroups (1= BMI 40 kg/m2). As seen in figure 1, those with a BMI of > 40 kg/m2 were at significantly increased risk of RHF. Conclusion An increased incidence of RHF after LVAD without a concurrent increase in mortality is seen in our patients with a BMI > 40 kg/m2. Strategies for peri-operative and long-term management should take this finding into consideration. Further investigation on a larger, multi-center scale is warranted.

© Oxford University Press 2018, All rights reserved. This paper investigates Lord King's contributions in light of the renewed debate on international monetary policy coordination. We argue that King's work contains refined bullionist insights concerning currency depreciation, exchange rate determination, and balance of payments adjustment. We show how King's analysis of the monetary process under different currency regimes can help elucidate the effects of unconventional monetary policy on a global scale, concerning monetary spillovers, currency wars, business cycles, and the distribution of wealth.