Faculty Bibliography

Glucose 6-phosphate dehydrogenase (G6PD) deficiency facilitates human coronavirus infection due to glutathione depletion. G6PD deficiency may especially predispose to hemolysis upon coronavirus disease-2019 (COVID-19) infection when employing pro-oxidant therapy. However, glutathione depletion is reversible by N-acetylcysteine (NAC) administration. We describe a severe case of COVID-19 infection in a G6PD-deficient patient treated with hydroxychloroquine who benefited from intravenous (IV) NAC beyond reversal of hemolysis. NAC blocked hemolysis and elevation of liver enzymes, C-reactive protein (CRP), and ferritin and allowed removal from respirator and veno-venous extracorporeal membrane oxygenator and full recovery of the G6PD-deficient patient. NAC was also administered to 9 additional respirator-dependent COVID-19-infected patients without G6PD deficiency. NAC elicited clinical improvement and markedly reduced CRP in all patients and ferritin in 9/10 patients. NAC mechanism of action may involve the blockade of viral infection and the ensuing cytokine storm that warrant follow-up confirmatory studies in the setting controlled clinical trials.

We conducted a retrospective review of thoracic transplant recipients (22 heart and 16 lung transplant recipients) prospectively enrolled in a single-center observational study of HCV NAT+ organ transplantation in HCV NAT- recipients. All recipients were treated with 8 weeks of glecaprevir-pibrentasvir (GP) for HCV viremia in addition to standard triple immunosuppression post-transplant. Thoracic transplant recipients of HCV NAT- organs were used as a control (24 heart and 22 lung transplant recipients). Our primary outcome was to assess the effect of GP on tacrolimus dose requirements. Secondary objectives included assessing drug interactions with common post-transplant medications, adverse effects, and the need to hold or discontinue GP therapy. The median tacrolimus concentration-to-dose (CDR) in the cohort was 184 (99-260) during GP therapy and 154 (78-304) over the first month after GP (p=0.79). Trends in median tacrolimus CDR were similar on a per-week basis and per-patient basis. In three instances, concomitant posaconazole and GP led to hyperbilirubinemia and interruption of posaconazole. GP therapy was held in one heart transplant recipient, and discontinued in another, due to unresolving hyperbilirubinemia. Utilization of GP to treat HCV viremia post-thoracic transplant is feasible and safe, but requires modifications to post-transplant pharmacotherapy and careful monitoring for adverse effects.

PURPOSE/OBJECTIVE:The right ventricular outflow tract (RVOT) velocity time integral (VTI), an echocardiographic measure of stroke distance, correlates with cardiac index. We sought to determine the prognostic significance of low RVOT VTI on clinical outcomes among patients with acute pulmonary embolism (PE). MATERIALS AND METHODS/METHODS:We conducted a retrospective review of echocardiograms on Pulmonary Embolism Response Team (PERT) activations at our institution. The main outcome was a composite of death, cardiac arrest, or hemodynamic deterioration. RESULTS:Of 188 patients, 30 met the combined outcome (16%) and had significantly lower RVOT VTI measurements (9.0 cm v 13.4 cm, p < 0.0001). The AUC for RVOT VTI at a cutoff of 10 cm was 0.78 (95% CI 0.67-0.90) with a sensitivity, specificity, negative predictive value, and positive predictive value of 0.72, 0.81, 0.94, and 0.42, respectively. Fifty-two patients of the cohort were classified as intermediate-high-risk PE and 21% of those met the combined outcome. RVOT VTI was lower among outcome positive patients (7.3 cm v 10.7 cm, p = 0.02). CONCLUSIONS:Low RVOT VTI is associated with poor clinical outcomes among patients with acute PE.

Controlled heart donation after circulatory determination of death (cDCD) is well-established internationally with good outcomes and could be adopted in the United States to increase heart supply if ethical and logistical challenges are comprehensively addressed. The most effective and resource-efficient method for mitigating warm ischemia after circulatory arrest is normothermic regional perfusion (NRP) in situ. This strategy requires restarting circulation after declaration of death according to circulatory criteria, which appears to challenge the legal circulatory death definition requiring irreversible cessation. Permanent cessation for life-saving efforts must be achieved to assuage this concern and ligating principal vessels maintains no blood flow to the brain, which ensures natural progression to cessation of brain function. This practice - standard in some countries - raises unique concerns about prioritizing life-saving efforts, informed authorization from decision-makers, and the clinician's role in the patient's death. To preserve public trust, medical integrity, and respect for the donor, the donation conversation must not take place until after an un-coerced decision to withdraw life-sustaining treatment made in accordance with the patient's treatment goals. The decision maker(s) must understand cDCD procedure well enough to provide genuine authorization and the preservation/procurement teams must be kept separate from the clinical care team.

Study: The Impella (Abiomed, Danvers, MA) ventricular support system is a family of temporary mechanical circulatory support devices designed to treat patients with cardiogenic shock. These devices include the percutaneously implanted 2.5/CP and the surgically implanted 5.0/LD. Data to assess adverse outcomes and help guide decision-making between Impella CP and 5.0/LD devices is limited. The purpose of this study was to compare the characteristics and clinical outcomes between Impella CP and 5.0/LD at our institution.
Method(s): From December 1, 2014 to October 31, 2019 a total of 117 patients underwent Impella implantation regardless of indication or device type. Of these, 82 patients were supported for greater than 24-hour duration. Baseline patient characteristics and outcomes were reviewed retrospectively. Groups were stratified based on either initial Impella CP or 5.0/LD placement and their clinical outcomes compared.
Result(s): Impella CP was implanted in 56 patients (median age: 60.5 years, male 71.4%) and Impella 5.0/LD (median age: 65.5 years, male 84.6%) were implanted in 26 patients. Regardless of the indication for Impella placement, 24 patients with Impella CP required additional mechanical support and were upgraded to either Impella 5.0/LD or extracorporeal membrane oxygenation (ECMO) (p=0.005). Patients with Impella CP had increased incidence of hemolysis defined as the presence of gross hematuria and elevated lactated dehydrogenase (Table 1). Patients with Impella 5.0/LD were more likely to survive from Impella and survive to discharge. Data from this study suggests that Impella 5.0/LD may have a more favorable device-specific adverse event profile compared to Impella CP

Study: Despite advances in design and hemocompatibility, pump thrombosis remains a significant cause of morbidity for patients implanted with durable left ventricular assist devices (LVAD). Pharmacologic fibrinolysis may be preferred as initial therapy because it obviates a surgical procedure. Yet, it historically has been associated with a significant risk of secondary intracerebral hemorrhage (ICH).
Method(s): We implemented a novel protocol to treat HVAD pump thrombosis and minimize risk of ICH that consisted of the following: initiation of a non-titrating heparin infusion at 500 units/hr; normalization of international normalized ratio (INR) by giving a flat dose of 1,000 units of four-factor prothrombin complex concentration (4F-PCC); and administration of alteplase as a 10 mg bolus followed by 40 mg given over 3 hours.
Result(s): Two patients underwent treatment with the above protocol for presumed HVAD pump thrombosis based on clinical signs of hemolysis and elevations of power on log-file analysis. One patient was 2 months from HVAD implant and the other 13 months. Both patients had subtherapeutic INR in the preceding weeks. Following administration of alteplase, log-file analysis demonstrated immediate resolution of power elevations (Fig. 1). Both patients had a subsequent rise in power requiring repeat alteplase dosing. No bleeding or thrombotic events occurred with treatment. One patient underwent heart transplant a month after treatment and is doing well; the second patient is stable on HVAD support 4 months following alteplase. Combining 4F-PCC to temporarily normalize the INR with repeat dosing of alteplase was effective at resolving HVAD pump thrombosis without bleeding complications and should be investigated further

BACKGROUND:The use of direct acting antivirals (DAA) has expanded transplantation from hepatitis C viremic donors (HCV-VIR). Our team has conducted an open-label, prospective trial to assess outcomes transplanting HCV-viremic hearts. Glecaprevir/Pibrentasvir (GLE/PIB) was our sole DAA. METHODS:Serial quantitative hepatitis C virus (HCV) RNA PCR was obtained to assess HCV viral titers. Between January 2018 to June 2019, a total of 50 recipients were transplanted. Of these, 22/50 (44%) were from HCV-VIR, the remaining 28 from non-viremic (HCV NON-VIR) donors. An 8 week course of GLE/PIB was initiated at 1 week post-transplant. RESULTS:There was no difference in demographic or clinical parameters between groups. All 22 recipients of HCV-VIR transplants became viremic. GLE/PIB was effective in decreasing viremia to undetectable levels by 6 weeks post-transplant in all patients. The median time to first undetectable HCV quantitative PCR was (4.3 weeks, IQR: 4-5.7 weeks). All patients demonstrated sustained undetectable viral load through 1 year follow up. There was no difference in survival at one year between HCV NON-VIR 28/28: (100%) vs. HCV-VIR 21/22 (95%) recipients. CONCLUSIONS:Our center reports excellent outcomes in transplanting utilizing hearts from HCV-VIR donors. No effect on survival or co-morbidity was found. An 8 week GLE/PIB course was safe and effective when initiated approximately 1 week post-transplant.

Mechanical blood-immersed bearings have been used in many continuous-flow rotary blood pumps to reduce friction between relatively moving parts, but their use has been associated with a significant incidence of pump thrombosis. As newer cardiac assist devices with more advanced bearings become available, the rate of pump thrombosis will likely decrease. Nevertheless, it is important to understand the design limitations of mechanical bearings as pumps utilizing them are still in use as chronic support devices and especially in the acute setting for temporary support devices. A properly designed journal bearing should support the spinning rotor with no surface-to-surface contact between the bearing and journal surfaces. The journal continuously undergoes orbital motion within the bearing, which can be "stable" or "unstable." Unstable orbital motion causes the journal to move progressively off-center until it collides with the bearing, and even minor variations in manufacturing can create off-design operation and dynamic instability of the journal. Since blood is the lubricant in most clinically-used rotary blood pumps, lubricant viscosity can vary abruptly in response to changes in hematocrit or plasma protein concentration. Additionally, shear stress from the high-speed rotor can cause hemolysis and plasma protein denaturation. We reviewed theoretical design and operating principles of mechanical bearings and discuss why the phenomenon of mechanical bearing thrombosis may be an inherent design issue dependent on variables that are beyond the control of clinicians.

Purpose: Intra-aortic balloon pumps (IABPs) can be used to provide hemodynamic support in patients with end-stage heart failure. IABPs are commonly inserted via the femoral artery, which can limit patients' mobility. The Ramsey Protocol, developed by a critical care Physical Therapist (PT), allows patients with femoral IABPs to safely transfer out of bed to a standing position using a tilt table. Our institution adapted this protocol to create a clinical practice guideline for ambulating patients with femoral IABPs.
Method(s): Our team's guideline included key components of the Ramsey Protocol, such as assessment of the patient's pre-morbid function, strength, and medical stability, as well as monitoring of IABP augmentation, IABP waveforms pre- and post-mobilization, and tilt table follow during ambulation. Appropriate candidates were patients with stable hemodynamics who were ambulatory prior to IABP placement, demonstrated against gravity muscle strength, and followed multi-step instructions.
Result(s): From April 1, 2019 to August 31, 2019, 9 patients (mean age 57 +/- 15 years) underwent IABP insertion via either right or left femoral artery, as a bridge to transplant, and were mobilized following our protocol for a total of 27 ambulation sessions (Table). There were no adverse events associated with ambulation, defined as changes in IABP augmentation, waveform, and positioning, or bleeding requiring transfusion. The mean time from IABP to ambulation was 2 +/- 2 days. All patients were successfully transplanted with mean time of IABP support of 6 +/- 3 days and all were alive at 30 days post-transplant. There were no complications during IABP support (i.e. limb ischemia, hemorrhage, stroke, device dislodgement or failure, end-organ dysfunction, or balloon rupture).
Conclusion(s): Early mobilization in select patients with femoral IABPs can be performed safely and successfully, avoiding the deleterious effects of bedrest that have been historically seen in this patient population.
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