Faculty Bibliography

Purpose: Heart transplantation (HTx) from hepatitis C virus (HCV) positive donors to HCV negative recipients may reduce waitlist time and increase access to viable organs. Direct acting antivirals (DAAs) are highly successful at curing HCV infection, but the effect of DAAs on the pharmacokinetics of calcineurin inhibitors is largely unknown. We describe the effect on tacrolimus dosage requirements in recipients of HCV viremic donors. Method(s): We retrospectively reviewed HCV negative HTx patients who received a HCV positive organ. All patients received an 8 week course of glecaprevir-pibrentasvir (GP) for HCV treatment and were on standard triple immunosuppression therapy. Patients receiving concomitant medications that affect tacrolimus metabolism were excluded. All tacrolimus dosages and trough levels were collected from the time of initiation post-HTx until 1 month after completion of GP treatment. Tacrolimus dose normalized concentrations using the concentration:dose ration (ng/mL:mg/kg) were compared before, during, and after GP treatment. Result(s): Seven HTx recipients were included in the analysis. Tacrolimus dose normalized concentrations were 124.8, 163.4, and 196.7 (ng/mL)/(mg/kg/d) before, during and after GP treatment, respectively (Figure 1). Tacrolimus dosage requirements did not differ during GP treatment as compared to before or after GP treatment. The percentage of tacrolimus trough levels within goal range and the incidence of supratherapeutic tacrolimus levels, was 51% vs. 41% and 4% vs. 0% during GP treatment as compared to after GP treatment. Conclusion(s): We did not find a difference in tacrolimus dosage requirements while receiving GP treatment as compared to before or after GP treatment; however, this study was limited by a small sample size. No empiric dosage adjustments can be recommended when initiating or discontinuing GP treatment at this time. Further data will be needed to strengthen these findings.

Control of mechanical circulatory support pump output typically requires that pressure-regulating functions be accomplished by active control of the speed or geometry of the device, with feedback from pressure or flow sensors. This article presents a different design approach, with a pressure-regulating device as the core design feature, allowing the essential control function of regulating pressure to be directly programmed into the hydromechanical design. We show the step-by-step transformation of a pressure-regulating device into a continuous-flow total artificial heart that passively balances left and right circulations without the need for pressure and flow sensors. In addition, we discuss a ventricular assist device that prevents backflow in the event of power interruption and also dynamically interacts with residual ventricle function to preserve pulsatility.

Anemia is common in patients with mechanical circulatory support and is associated with increased morbidity. Repletion using parenteral iron infusions has been proven to be beneficial in patients with heart failure. In this report, we describe a case of increased power and flows of continuous-flow left ventricular assist device (LVAD) during an iron dextran infusion. We subsequently studied the effects of iron dextran infusion in an in vitro LVAD mock circulatory loop. The observed increase in flow and power was most likely due to drug-patient interaction rather than drug-LVAD interaction. Mock loops and in vivo animal models may be necessary for proactive evaluation of the safety of intravenous (IV) preparations in this patient population.

PURPOSE/OBJECTIVE:Psychosocial assessment of patients comprises an important element in the selection process of appropriate candidates for left ventricular assist device (LVAD) implantation. We sought to determine the association of the well-validated psychosocial assessment of candidates for transplantation (PACT) scale to clinical outcomes post-LVAD implantation. MATERIALS AND METHODS/METHODS:The PACT scale was used retrospectively to reconstruct psychosocial profiles of all patients who underwent a continuous-flow LVAD implantation for all indications at our institution between March 2008 and August 2012 (N = 230). Psychosocial elements including social support, psychological health, lifestyle factors, comprehension of the operation, and follow-up were evaluated. The primary outcome was overall survival, and the secondary outcomes were hospital readmission, pump thrombosis, hemolysis, gastrointestinal (GI) bleeding, and LVAD driveline infections. RESULTS:The mean age of patients was 55.3 years, with 83% being male; 58% (N = 135) were bridge to transplant and 42% (N = 95) were destination therapy. Up to 1-year post-LVAD implant, there were no statistical differences among the 5 PACT candidate groups in terms of survival ( P = .79), hospital readmissions ( P = .55), suspected or confirmed pump thrombosis ( P = .31), hemolysis ( P = .43), GI bleeding ( P = .71), or driveline infections ( P = .06). CONCLUSIONS:In this single-center retrospective review, post hoc reconstruction of psychosocial profiles using the PACT scale and independent assessment of postimplant outcomes, including survival and adverse events, did not show any association. However, given the small number of patients in the low score PACT groups as well as limited duration of follow-up, further studies are required to elucidate the association.

Introduction: Cardiogenic shock is associated with high in-hospital mortality rates regardless of etiology. Recently, there has been an increase in utilization of acute mechanical circulatory support (MCS) in patients with cardiogenic shock. Although there is no consensus as to the most appropriate device for any particular patient presentation, acute MCS devices have been widely adopted in institutions that favor an aggressive approach to cardiogenic shock. Establishment of an Adult ECMO Program at our institution has led to experience with additional acute MCS devices. The complexity of these clinical situations led to the creation of a multidisciplinary team, including a combination of cardiologists, surgeons, interventionalists, and intensivists, committed to treating these patients. As an early ECMO Program and Cardiogenic Shock Team, we sought to review our early experience with acute MCS for cardiogenic shock to define our baseline strategies and outcomes in this patient population. Materials and Methods: We completed a retrospective review of cardiogenic shock patients who were treated with acute MCS by Fiscal Year (September 1 to August 31) beginning with Fiscal Year (FY) 2014. We reviewed implant volume by device, including temporary surgical ventricular assist device (VAD), percutaneous and surgical Impella, percutaneous RVADs, and veno-arterial Extracorporeal Membrane Oxygenation (VA-ECMO). Data collected included etiology of shock, indication for device implantation, type of support offered, length of support, and outcome of support. For each category of device, we also reviewed our outcomes by mirroring the established ELSO benchmarks of "Survival from ECMO" and "Survival to Discharge." Results: We found a steady increase in the use of acute MCS for treatment of cardiogenic shock from FY 2014 to FY 2018. From FY 2014 to 2015 there was an increase from zero to 18 implants. The following year (FY 2016) revealed a 100% increase, with a total of 36 implants. The volume increased more slowly (16%/year) the following two years (FY 2017, FY 2018) with 43 and 48 implants, respectively. Overall outcome assessment revealed that 68% of patients survived acute MCS and 53% of patients survived to hospital discharge with an increased survival to discharge in the last fiscal year to 62%. Conclusion: Creation of an Adult ECMO Program and a multidisciplinary Cardiogenic Shock Team correlated with an increase in the number of patients supported with acute MCS. As the team gains experience with these patients and the devices available to support them, we expect the outcomes to continue to improve. Patient selection, surgical approaches and techniques, standardizing medical therapy, and managing and reducing complications will give these patients the best opportunity to survive

OBJECTIVES/OBJECTIVE:Mechanical circulatory support has become standard therapy for adult patients with end-stage heart failure; however, in paediatric patients with congenital heart disease, the options for chronic mechanical circulatory support are limited to paracorporeal devices or off-label use of devices intended for implantation in adults. Congenital heart disease and cardiomyopathy often involve both the left and right ventricles; in such cases, heart transplantation, a biventricular assist device or a total artificial heart is needed to adequately sustain both pulmonary and systemic circulations. We aimed to evaluate the in vitro performance of the initial prototype of our paediatric continuous-flow total artificial heart. METHODS:The paediatric continuous-flow total artificial heart pump was downsized from the adult continuous-flow total artificial heart configuration by a scale factor of 0.70 (1/3 of total volume) to enable implantation in infants. System performance of this prototype was evaluated using the continuous-flow total artificial heart mock loop set to mimic paediatric circulation. We generated maps of pump performance and atrial pressure differences over a wide range of systemic vascular resistance/pulmonary vascular resistance and pump speeds. RESULTS:Performance data indicated left pump flow range of 0.4-4.7 l/min at 100 mmHg delta pressure. The left/right atrial pressure difference was maintained within ±5 mmHg with systemic vascular resistance/pulmonary vascular resistance ratios between 1.4 and 35, with/without pump speed modulation, verifying expected passive self-regulation of atrial pressure balance. CONCLUSIONS:The paediatric continuous-flow total artificial heart prototype met design requirements for self-regulation and performance; in vivo pump performance studies are ongoing.

PURPOSE OF REVIEW/OBJECTIVE:Many patients suffer from either persistent right ventricular failure (RVF) at the time of left ventricular assist device (LVAD) or have ongoing symptoms consistent with RVF during chronic mechanical circulatory support. The lack of long-term right ventricular assist devices (RVADs) has limited the impact that mechanical circulatory support can provide to patients with biventricular failure. We aim to review the entire spectrum of RVF in patients receiving LVADs and reflect on why this entity remains the Achilles' heel of LVAD therapy. RECENT FINDINGS/RESULTS:In the early postoperative period, LVAD implantation reduces right ventricle (RV) afterload, but RV dysfunction may be exacerbated secondary to increased venous return. With prolonged therapy, the decreased RV afterload leads to improved RV contractile function. Bayesian statistical models outperform previously published preoperative risk scores by considering inter-relationships and conditional probabilities amongst independent variables. Various echocardiographic parameters and the pulmonary artery pulsatility index have shown promise in predicting post-LVAD RVF. Recent publications have delineated the emergence of 'delayed' RVF. Several devices are currently being investigated for use as RVADs. SUMMARY/CONCLUSIONS:Post-LVAD RVF depends on the RV's ability to adapt to acute hemodynamic changes imposed by the LVAD. Management options are limited due to the lack of an easily implantable, chronic-use RVAD.