Impact of Donor Hemodynamics on Recipient Survival in Heart Transplantation.

BACKGROUND: Heart transplantation is the gold-standard therapy for end-stage heart failure, but rates of donor-heart use remain low due to various factors that are often not evidence based. The impact of donor hemodynamics obtained via right-heart catheterization on recipient survival remains unclear. METHODS: The United Network for Organ Sharing registry was used to identify donors and recipients from September 1999-December 2019. Donor hemodynamics data were obtained and analyzed using univariate and multivariable logistical regression, with the primary endpoints being 1- and 5-year post-transplant survival. RESULTS: Of the 85,333 donors who consented to heart transplantation during the study period, 6573 (7.7%) underwent right-heart catheterization, of whom 5531 eventually underwent procurement and transplantation. Donors were more likely to undergo right-heart catheterization if they had high-risk criteria. Recipients who had donor hemodynamic assessment had 1- and 5-year survival rates similar to those without donor hemodynamic assessment (87% vs 86%, 1 year). Abnormal hemodynamics were common in donor hearts but did not impact recipient survival rates, even when risk-adjusted in multivariable analysis. CONCLUSIONS: Donors with abnormal hemodynamics may represent an opportunity to expand the pool of viable donor hearts.

Discovery of non-HLA antibodies associated with cardiac allograft rejection and development and validation of a non-HLA antigen multiplex panel: From bench to bedside.

We analyzed humoral immune responses to nonhuman leukocyte antigen (HLA) after cardiac transplantation to identify antibodies associated with allograft rejection. Protein microarray identified 366 non-HLA antibodies (>1.5 fold, P < .5) from a discovery cohort of HLA antibody-negative, endothelial cell crossmatch-positive sera obtained from 12 cardiac allograft recipients at the time of biopsy-proven rejection. From these, 19 plasma membrane proteins and 10 autoantigens identified from gene ontology analysis were combined with 48 proteins identified through literature search to generate a multiplex bead array. Longitudinal sera from a multicenter cohort of adult cardiac allograft recipients (samples: n = 477 no rejection; n = 69 rejection) identified 18 non-HLA antibodies associated with rejection (P < .1) including 4 newly identified non-HLA antigenic targets (DEXI, EMCN, LPHN1, and SSB). CART analysis showed 5/18 non-HLA antibodies distinguished rejection vs nonrejection. Antibodies to 4/18 non-HLA antigens synergize with HLA donor-specific antibodies and significantly increase the odds of rejection (P < .1). The non-HLA panel was validated using an independent adult cardiac transplant cohort (n = 21 no rejection; n = 42 rejection, >1R) with an area under the curve of 0.87 (P < .05) with 92.86% sensitivity and 66.67% specificity. We conclude that multiplex bead array assessment of non-HLA antibodies identifies cardiac transplant recipients at risk of rejection.

Evaluation of anticoagulation and nonsurgical major bleeding in recipients of continuous-flow left ventricular assist devices.

Continuous-flow left ventricular assist device (LVAD) placement has become a standard of care in advanced heart failure treatment. Bleeding is the most frequently reported adverse event after LVAD implantation and may be increased by antithrombotic agents used for prevention of pump thrombosis. This retrospective cohort included 85 adult patients implanted with a Heartmate II LVAD. Major bleeding was defined as occurring >7 days after implant and included intracranial hemorrhage, events requiring 2 units of packed red blood cells within a 24-h period, and death from bleeding. Primary outcome was intensity of anticoagulation between patients with or without at least one incidence of nonsurgical major bleeding. Major bleeding occurred in 35 (41%) patients with 0.48 events per patient year and a median (IQR) time to first bleed of 134.5 (39.3, 368.5) days. The median (IQR) INR at time of bleed was 1.7 (1.4, 2.5). Median INR during follow-up did not differ between groups and patients with major bleeding were not more likely to have a supra-therapeutic INR. Patients who bled were more likely to have received LVAD for destination therapy, to have lower weight, worse renal function, and lower hemoglobin at baseline. Duration of LVAD support and survival were similar between groups with no difference in occurrence of thrombosis. Incidence of nonsurgical major bleeding was not significantly associated with degree of anticoagulation. Certain baseline characteristics may be more important than anticoagulation intensity to identify patients at risk for bleeding after LVAD implant. Modification of anticoagulation alone is not a sufficient management strategy and early intervention may be required to mitigate bleeding impact.

A Ventricular Assist Device Recipient and Suicidality: Multidisciplinary Collaboration With a Psychiatrically Distressed Patient.

BACKGROUND: Ventricular assist device (VAD) recipients are at high risk of depression and anxiety, and poor psychosocial functioning is associated with worse medical outcomes. PURPOSE: We present a case of a 31-year-old depressed patient who demonstrated passive suicidal behavior through multiple episodes of noncompliance, including temporarily discontinuing warfarin (Coumadin) several months after VAD implantation. The patient's psychosocial and medical histories and outcomes are presented. CONCLUSIONS: This case underscores the importance of pre-VAD as well and ongoing psychosocial evaluation and management for this unique patient population. CLINICAL IMPLICATIONS: Medical teams who are treating patients with cardiovascular disease who are under consideration for VAD or heart transplantation need to be aware of the multitude of ways in which patients can express depressed and suicidal mood and work with a multidisciplinary team to treat such symptoms to optimize patients' success with VAD/heart transplantation.

Thyroid hormone use during cardiac transplant organ procurement.

BACKGROUND: Acute hypothyroidism after brain death results in hemodynamic impairments that limit availability of donor hearts. Thyroid hormone infusions can halt that process and lead to increased utilization of donor organs, but prolonged use of thyroid replacement has not been well studied. METHODS: We developed a 15-question survey regarding policies, procedures, and reporting of thyroid hormone use by organ procurement organizations (OPOs). The survey was posted for 5 weeks on the Association of OPOs Portal. RESULTS: We received 29 responses, representing 24 OPOs. Seventy-two percent reported their OPOs use thyroid hormone for all potential donors and 90% have a protocol for thyroid hormone use. There is a large variation in the maximum dose of thyroid hormone used, and many OPOs have no weaning protocol. Most OPOs do not collect data on total thyroid hormone administered during procurement and would favor more detailed report of thyroid hormone use. CONCLUSIONS: Thyroid hormone use can have important implications for organ selection and cardiac function before and after transplantation. Protocols vary widely with respect to why and how to use and wean thyroid hormone. We believe there should be more detailed reporting of thyroid hormone use for future studies to ensure appropriate donor management.

Need for cardiac implantable electronic devices and long-term follow-up in recipients of orthotopic heart transplants.

BACKGROUND: Cardiac pacemaker implantation after orthotopic heart transplantation declined dramatically after development of the bicaval anastomosis technique. However, much less is known about the rate, indications, and predictors of device implantation procedures with the current surgical technique. OBJECTIVE: The purpose of this study was to evaluate the indications, patient characteristics, incidence, and survival related to cardiac implantable electronic device (CIED) implantation after heart transplantation. METHODS: This was a single-center study of 399 consecutive adult recipients of orthotopic heart transplants with bicaval anastomosis from 1991 to 2017. The primary end point was freedom from pacemaker or implantable cardioverter-defibrillator (ICD) implantation, and the secondary end point was all-cause mortality. RESULTS: At the time of transplantation, the mean age of recipients was 50 ± 12 years and that of donors 31 ± 12 years. CIEDs were implanted in 8% of recipients (n = 31): 11 pacemakers (35%) for sinus node dysfunction, 17 (55%) for high-grade heart block, and 3 ICDs (10%) for the primary prevention of sudden cardiac death. Early CIED implantation (<30 days) was rare and absent for sinus node dysfunction. The risk for CIED implantation increased progressively during follow-up (0-30 years; median 11 years), with low-, moderate-, and high-risk periods between 0 and 10, between 10 and 20, and between 20 and 30 years, respectively. Recipients receiving CIEDs survived longer after transplantation (21 years vs 13 years; P < .01). Recipients receiving pacemakers for heart block were more likely to receive older donor hearts at the time of transplantation. CONCLUSION: The risk of pacemaker implantation increases progressively, while ICD implantation is rare. Donor age is the predominant risk factor for subsequent heart block. Early sinus node dysfunction requiring permanent pacing is rare.

Surveillance with dual noninvasive testing for acute cellular rejection after heart transplantation: Outcomes from the Surveillance HeartCare Outcomes Registry.

BACKGROUND: Molecular testing with gene-expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) is increasingly used in the surveillance for acute cellular rejection (ACR) after heart transplant. However, the performance of dual testing over each test individually has not been established. Further, the impact of dual noninvasive surveillance on clinical decision-making has not been widely investigated. METHODS: We evaluated 2,077 subjects from the Surveillance HeartCare Outcomes Registry registry who were enrolled between 2018 and 2021 and had verified biopsy data and were categorized as dual negative, GEP positive/dd-cfDNA negative, GEP negative/dd-cfDNA positive, or dual positive. The incidence of ACR and follow-up testing rates for each group were evaluated. Positive likelihood ratios (LRs+) were calculated, and biopsy rates over time were analyzed. RESULTS: The incidence of ACR was 1.5% for dual negative, 1.9% for GEP positive/dd-cfDNA negative, 4.3% for GEP negative/dd-cfDNA positive, and 9.2% for dual-positive groups. Follow-up biopsies were performed after 8.8% for dual negative, 14.2% for GEP positive/dd-cfDNA negative, 22.8% for GEP negative/dd-cfDNA positive, and 35.4% for dual-positive results. The LR+ for ACR was 1.37, 2.91, and 3.90 for GEP positive, dd-cfDNA positive, and dual-positive testing, respectively. From 2018 to 2021, biopsies performed between 2 and 12-months post-transplant declined from 5.9 to 5.3 biopsies/patient, and second-year biopsy rates declined from 1.5 to 0.9 biopsies/patient. At 2 years, survival was 94.9%, and only 2.7% had graft dysfunction. CONCLUSIONS: Dual molecular testing demonstrated improved performance for ACR surveillance compared to single molecular testing. The use of dual noninvasive testing was associated with lower biopsy rates over time, excellent survival, and low incidence of graft dysfunction.

Bayesian analysis of recurrent event with dependent termination: an application to a heart transplant study.

For a heart transplant patient, the risk of graft rejection and risk of death are likely to be associated. Two fully specified Bayesian models for recurrent events with dependent termination are applied to investigate the potential relationships between these two types of risk as well as association with risk factors. We particularly focus on the choice of priors, selection of the appropriate prediction model, and prediction methods for these two types of risk for an individual patient. Our prediction tools can be easily implemented and helpful to physicians for setting heart transplant patients' biopsy schedule.

Hemodynamic Effects of High-dose Levothyroxine and Methylprednisolone in Brain-dead Potential Organ Donors.

BACKGROUND: Hormonal replacement therapy is administered to many brain-dead organ donors to improve hemodynamic stability. Previous clinical studies present conflicting results with several randomized studies reporting no benefit. METHODS: Consecutive adult donors (N = 199) were randomized to receive high-dose levothyroxine, high-dose methylprednisolone, both (Combo), or no hormonal therapy (Control). Vasopressor requirements using the vasoactive-inotropic score (VIS) were assessed at baseline, 4 h, and at procurement. Crossover to the Combo group was sufficient to require separate intention-to-treat and per-protocol analyses. RESULTS: In the intention-to-treat analysis, the mean (±SD) reduction in VIS from baseline to procurement was 1.6 ± 2.6, 14.9 ± 2.6, 10.9 ± 2.6, and 7.1 ± 2.6 for the levothyroxine, methylprednisolone, Combo, and Control groups, respectively. While controlling for the baseline score, the reduction in VIS was significantly greater in the methylprednisolone and Combo groups and significantly less in the levothyroxine group compared with controls. Results were similar in the per-protocol analysis. CONCLUSIONS: High-dose methylprednisolone alone or in combination with levothyroxine allowed for significant reduction in vasopressor support in organ donors. Levothyroxine alone offered no advantage in reducing vasopressor support. Organ yield, transplantation rates, and recipient outcomes were not adversely affected.

Continuous versus intermittent infusion of furosemide in acute decompensated heart failure.

BACKGROUND: Despite advances in the treatment of chronic ambulatory heart failure, hospitalization rates for acute decompensated heart failure (ADHF) remain high. Although loop diuretics are used in nearly all patients with ADHF to relieve congestive symptoms, optimal dosing strategies remain poorly defined. METHODS AND RESULTS: This was a prospective, randomized, parallel-group study comparing the effectiveness of continuous intravenous (cIV) with intermittent intravenous (iIV) infusion of furosemide in 56 patients with ADHF. The dose and duration of furosemide as well as concomitant medications to treat ADHF were determined by physician preference. The primary end point of the study was net urine output (nUOP)/24 hours. Safety measures including electrolyte loss and hemodynamic instability were also assessed. Twenty-six patients received cIV and 30 patients received iIV dosing. The mean nUOP/24 hours was 2098+/-1132 mL in patients receiving cIV versus 1575+/-1100 mL in the iIV group (P=.086). The cIV group had significantly greater total urine output (tUOP) with 3726+/-1121 mL/24 hours versus 2955+/-1267 mL/24 hours in the iIV group (P=.019) and tUOP/mg furosemide with 38.0+/-31.0 mL/mg versus 22.2+/-12.5 mL/mg (P=.021). Mean weight loss was not significantly different between the groups. The cIV group experienced a shorter length of hospital stay (6.9+/-3.7 versus 10.9+/-8.3 days, P=.006). There were no differences in safety measures between the groups. CONCLUSIONS: The cIV of furosemide was well tolerated and significantly more effective than iIV for tUOP. In addition, continuous infusion appears to provide more efficient diuresis.

Effects of Percutaneous LVAD Support on Right Ventricular Load and Adaptation.

Both operative and hemodynamic mechanisms have been implicated in right heart failure (RHF) following surgical left ventricular assist device (LVAD) implantation. We investigated the effects of percutaneous LVAD (pLVAD; Impella®, Abiomed) support on right ventricular (RV) load and adaptation. We reviewed all patients receiving a pLVAD for cardiogenic shock at our institution between July 2014 and April 2017, including only those with pre- and post-pLVAD invasive hemodynamic measurements. Hemodynamic data was recorded immediately prior to pLVAD implantation and up to 96 h post-implantation. Twenty-five patients were included. Cardiac output increased progressively during pLVAD support. PAWP improved early post-pLVAD but did not further improve during continued support. Markers of RV adaptation (right ventricular stroke work index, right atrial pressure (RAP), and RAP to pulmonary artery wedge pressure ratio (RAP:PAWP)) were unchanged acutely implant but progressively improved during continued pLVAD support. Total RV load (pulmonary effective arterial elastance; EA) and resistive RV load (pulmonary vascular resistance; PVR) both declined progressively. The relationship between RV load and RV adaptation (EA/RAP and EA/RAP:PAWP) was constant throughout. Median vasoactive-inotrope score declined after pLVAD placement and continued to decline throughout support. Percutaneous LVAD support in patients with cardiogenic shock did not acutely worsen RV adaptation, in contrast to previously described hemodynamic effects of surgically implanted durable LVADs. Further, RV load progressively declined during support, and the noted RV adaptation improvement was load-dependent as depicted by constant EA/RA and EA/RAP:PAWP relationships. These findings further implicate the operative changes associated with surgical LVAD implantation in early RHF following durable LVAD.

Pulmonary Arterial Elastance and INTERMACS-Defined Right Heart Failure Following Left Ventricular Assist Device.

BACKGROUND: Acute right heart failure (RHF) after left ventricular assist device implantation remains a major source of morbidity and mortality, yet the definition of RHF and the preimplant variables that predict RHF remain controversial. This study evaluated the ability of (1) INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) RHF classification to predict post-left ventricular assist device survival and (2) preoperative characteristics and hemodynamic parameters to predict severe and severe acute RHF. METHODS AND RESULTS: An international, multicenter study at 4 large academic centers was conducted between 2008 and 2016. All subjects with hemodynamics measured by right heart catheterization within 30 days before left ventricular assist device implantation were included. RHF was defined using the INTERMACS definition for RHF. In total, 375 subjects were included (mean age, 57.4±13.2 years, 54% bridge-to-transplant). Mild RHF was most common (34%), followed by moderate RHF (16%), severe RHF (13%), and severe acute RHF (9%). Estimated on-device survival rates at 2 years were 72%, 71%, and 55% in the patients with none, mild-to-moderate, and severe-to-severe acute RHF, respectively (P=0.004). In addition, the independent hazard ratio for mortality was only increased in the patients with severe-to-severe acute RHF (hazard ratio, 3.95; 95% CI, 2.16-7.23; P<0.001). INTERMACS-defined RHF was superior to postimplant inotrope duration alone in the prediction of all-cause mortality. In multivariable analysis, older age, lower INTERMACS classes, and higher pulmonary arterial elastance (ratio of systolic pulmonary artery pressure to stroke volume) before left ventricular assist device, were identified as significant predictors of severe-to-severe acute RHF. Stratifying patients by ratio of systolic pulmonary artery pressure to stroke volume and right atrial pressure significantly improved the discrimination between patients at risk for severe-to-severe acute RHF. CONCLUSIONS: The INTERMACS RHF classification correctly identifies patients at risk for mortality, though this risk is only increased in patients with severe-to-severe acute RHF. Several predictors for RHF were identified, of which ratio of systolic pulmonary artery pressure to stroke volume was the strongest hemodynamic predictor. Coupling ratio of systolic pulmonary artery pressure to stroke volume with right atrial pressure may be most helpful in identifying patients at risk for severe-to-severe acute RHF.

Daclizumab to prevent rejection after cardiac transplantation.

BACKGROUND: Daclizumab, a humanized monoclonal antibody against the interleukin-2 receptor, reduced the risk of rejection without increasing the risk of infection among renal-transplant recipients and, in a single-center trial, among cardiac-transplant recipients. We conducted a multicenter, placebo-controlled, double-blind study to confirm these results in cardiac-transplant patients. METHODS: We randomly assigned 434 recipients of a first cardiac transplant treated with standard immunosuppression (cyclosporine, mycophenolate mofetil, and corticosteroids) to receive five doses of daclizumab or placebo. The primary end point was a composite of moderate or severe cellular rejection, hemodynamically significant graft dysfunction, a second transplantation, or death or loss to follow-up within six months. RESULTS: By six months, 104 of 218 patients in the placebo group had reached the primary end point, as compared with 77 of the 216 patients in the daclizumab group (47.7 percent vs. 35.6 percent, P=0.007), a 12.1 percent absolute risk reduction and a 25 percent relative reduction. The rate of rejection was lower in the daclizumab group than in the placebo group (41.3 percent vs. 25.5 percent). Among patients reaching the primary end point, the median time to the end point was almost three times as long in the daclizumab group as in the placebo group during the first 6 months (61 vs. 21 days) and at 1 year (96 vs. 26 days). More patients in the daclizumab group than in the placebo group died of infection (6 vs. 0) when they received concomitant cytolytic therapy. CONCLUSIONS: Daclizumab was efficacious as prophylaxis against acute cellular rejection after cardiac transplantation. Because of the excess risk of death, concurrent or anticipated use of cytolytic therapy with daclizumab should be avoided.

Rational use of diuretics in acute decompensated heart failure.

Chronic heart failure poses an enormous health care burden to the United States and other developed countries. Acute decompensated heart failure (ADHF) accounts for nearly half of the morbidity and expense of treating this disease. Most patients presenting with ADHF have symptomatic vascular congestion. Diuretics, especially loop diuretics, are the primary pharmacologic intervention used in this population. Despite their widespread use, scant data from randomized clinical trials are available to guide therapeutic choices. In addition, data from several large registries examining weight loss during hospitalization for ADHF suggest that efficacy with diuretic treatment is far from universal. Aggressive diuresis carries a significant risk of electrolyte and volume depletion, with subsequent arrhythmias, hypotension, and worsening renal function. These complications often translate into worse prognosis. Diuretic regimens used to treat ADHF must be individualized based on general knowledge of potency and pharmacokinetic and pharmacodynamic considerations. This article summarizes older and more recent literature to provide a framework for making rational treatment choices in this difficult patient population.

A Phase 2a dose-escalation study of the safety, tolerability, pharmacokinetics and haemodynamic effects of BMS-986231 in hospitalized patients with heart failure with reduced ejection fraction.

AIMS: This study was designed to evaluate the safety, tolerability and haemodynamic effects of BMS-986231, a novel second-generation nitroxyl donor with potential inotropic, lusitropic and vasodilatory effects in patients hospitalized with decompensated heart failure and reduced ejection fraction (HFrEF). METHODS AND RESULTS: Forty-six patients hospitalized with decompensated HFrEF were enrolled into four sequential dose-escalation cohorts in this double-blind, randomized, placebo-controlled Phase 2a study. Patients with baseline pulmonary capillary wedge pressure (PCWP) of ≥20 mmHg and a cardiac index of ≤2.5 L/min/m2 received one 6-h i.v. infusion of BMS-986231 (at 3, 5, 7 or 12 µg/kg/min) or placebo. BMS-986231 produced rapid and sustained reductions in PCWP, as well as consistent reductions in time-averaged pulmonary arterial systolic pressure, pulmonary arterial diastolic pressure and right atrial pressure. BMS-986231 increased non-invasively measured time-averaged stroke volume index, cardiac index and cardiac power index values, and decreased total peripheral vascular resistance. There was no evidence of increased heart rate, drug-related arrhythmia or symptomatic hypotension with BMS-986231. Analyses of adverse events throughout the 30-day follow-up did not identify any toxicities specific to BMS-986231, with the potential exception of infrequent mild-to-moderate headaches during infusion. There were no treatment-related serious adverse events. CONCLUSIONS: BMS-986231 demonstrated a favourable safety and haemodynamic profile in patients hospitalized with advanced heart failure. Based on preclinical data and these study's findings, it is possible that the haemodynamic benefits may be mediated by inotropic and/or lusitropic as well as vasodilatory effects. The therapeutic potential of BMS-986231 should be further assessed in patients with heart failure.

Continuous aortic flow augmentation: a pilot study of hemodynamic and renal responses to a novel percutaneous intervention in decompensated heart failure.

BACKGROUND: Diminished aortic flow may induce adverse downstream vascular and renal signals. Investigations in a heart failure animal model have shown that continuous aortic flow augmentation (CAFA) achieves hemodynamic improvement and ventricular unloading, which suggests a novel therapeutic approach to patients with heart failure exacerbation that is inadequately responsive to medical therapy. METHODS AND RESULTS: We studied 24 patients (12 in Europe and 12 in the United States) with heart failure exacerbation and persistent hemodynamic derangement despite intravenous diuretic and inotropic and/or vasodilator treatment. CAFA (mean+/-SD 1.34+/-0.12 L/min) was achieved through percutaneous (n=19) or surgical (n=5) insertion of the Cancion system, which consists of inflow and outflow cannulas and a magnetically levitated and driven centrifugal pump. Hemodynamic improvement was observed within 1 hour. Systemic vascular resistance decreased from 1413+/-453 to 1136+/-381 dyne.s.cm(-5) at 72 hours (P=0.0008). Pulmonary capillary wedge pressure decreased from 28.5+/-4.9 to 19.8+/-7.0 mm Hg (P<0.0001), and cardiac index (excluding augmented aortic flow) increased from 1.97+/-0.44 to 2.27+/-0.43 L.min(-1).m(-2) (P=0.0013). Serum creatinine trended downward during treatment (overall P=0.095). There were 8 complications during treatment, 7 of which were self-limited. Hemodynamics remained improved 24 hours after CAFA discontinuation. CONCLUSIONS: In patients with heart failure and persistent hemodynamic derangement despite intravenous inotropic and/or vasodilator therapy, CAFA improved hemodynamics, with a reduction in serum creatinine. CAFA represents a promising, novel mode of treatment for patients who are inadequately responsive to medical therapy. The clinical impact of the observed hemodynamic improvement is currently being explored in a prospective, randomized, controlled trial.

Consensus conference report: maximizing use of organs recovered from the cadaver donor: cardiac recommendations, March 28-29, 2001, Crystal City, Va.

The shortage of available donor hearts continues to limit cardiac transplantation. For this reason, strict criteria have limited the number of patients placed on the US waiting list to approximately 6000 to 8000 per year. Because the number of available donor hearts has not increased beyond approximately 2500 per year, the transplant waiting list mortality rate remains substantial. Suboptimal and variable utilization of donor hearts has compounded the problem in the United States. In 1999, the average donor yield from 55 US regions was 39%, ranging from 19% to 62%. This report provides the detailed cardiac recommendations from the conference on "Maximizing Use of Organs Recovered From the Cadaver Donor" held March 28 to 29, 2001, in Crystal City, Va. The specific objective of the report is to provide recommendations to improve the evaluation and successful utilization of potential cardiac donors. The report describes the accuracy of current techniques such as echocardiography in the assessment of donor heart function before recovery and the impact of these data on donor yield. The rationale for and specific details of a donor-management pathway that uses pulmonary artery catheterization and hormonal resuscitation are provided. Administrative recommendations such as enhanced communication strategies among transplant centers and organ-procurement organizations, financial incentives for organ recovery, and expansion of donor database fields for research are also described.

Accurate monitoring of intravascular fluid volume: A novel application of intrathoracic impedance measures for the guidance of volume reduction therapy.

BACKGROUND: A significant proportion of patients admitted for acute decompensated heart failure (ADHF) that undergo volume reduction therapy are discharged with unchanged or increased bodyweight suggesting that the endpoints for these therapies are not optimally defined. We aimed to identify vectors that can help monitor changes in intravascular fluid volume, that in turn may more accurately guide volume reduction therapy. METHODS: Data from six different impedance vectors and corresponding changes in intravascular volume derived from changes in hematocrit were obtained from 132 clinical congestion events in 56 unique patients enrolled in a multisite trial of early detection of clinical congestion events (DEFEAT PE). Mixed effects regression models were used to determine the relation between changes in impedance derived from six different vectors and changes in intravascular plasma volume. RESULTS: Changes in impedance were negatively associated with changes in plasma volume. Two vectors, the right atrial ring to left ventricular ring and the left ventricular ring to the right ventricular ring, were most closely associated with changes in intravascular plasma volume. CONCLUSION: Impedance vectors derived from a multivector monitoring system reflect changes in intravascular plasma volume. Two of these vectors most closely track changes in plasma volume and may be used to more accurately guide and optimize volume reduction therapy.