Noninvasive Physiologic Assessment of Cardiac Allograft Vasculopathy Is Prognostic for Post-Transplant Events.

BACKGROUND: Cardiac allograft vasculopathy (CAV) causes impaired blood flow in both epicardial coronary arteries and the microvasculature. A leading cause of post-transplant mortality, CAV affects 50% of heart transplant recipients within 10 years of heart transplant. OBJECTIVES: This analysis examined the outcomes of heart transplant recipients with reduced myocardial blood flow reserve (MBFR) and microvascular CAV detected by 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging. METHODS: A total of 181 heart transplant recipients who underwent PET to assess for CAV were included with a median follow-up of 4.7 years. Patients were classified into 2 groups according to the total MBFR: >2.0 and ≤2.0. Microvascular CAV was defined as no epicardial CAV detected by PET and/or coronary angiography, but with an MBFR ≤2.0 by PET. RESULTS: In total, 71 (39%) patients had an MBFR ≤2.0. Patients with an MBFR ≤2.0 experienced an increased risk for all outcomes: 7-fold increase in death or retransplantation (HR: 7.05; 95% CI: 3.2-15.6; P < 0.0001), 12-fold increase in cardiovascular death (HR: 12.0; 95% CI: 2.64-54.12; P = 0.001), and 10-fold increase in cardiovascular hospitalization (HR: 10.1; 95% CI: 3.43-29.9; P < 0.0001). The 5-year mean survival was 302 days less than those with an MBFR >2.0 (95% CI: 260.2-345.4 days; P < 0.0001). Microvascular CAV (adjusted HR: 3.86; 95% CI: 1.58-9.40; P = 0.003) was independently associated with an increased risk of death or retransplantation. CONCLUSIONS: Abnormal myocardial blood flow reserve, even in the absence of epicardial CAV, identifies patients at a high risk of death or retransplantation. Measures of myocardial blood flow provide prognostic information in addition to traditional CAV assessment.

The difference between cystatin C- and creatinine-based assessment of kidney function in acute heart failure.

AIMS: Acute heart failure (HF) is associated with muscle mass loss, potentially leading to overestimation of kidney function using serum creatinine-based estimated glomerular filtration rate (eGFRsCr ). Cystatin C-based eGFR (eGFRCysC ) is less muscle mass dependent. Changes in the difference between eGFRCysC and eGFRsCr may reflect muscle mass loss. We investigated the difference between eGFRCysC and eGFRsCr and its association with clinical outcomes in acute HF patients. METHODS AND RESULTS: A post hoc analysis was performed in 841 patients enrolled in three trials: Diuretic Optimization Strategy Evaluation (DOSE), Renal Optimization Strategies Evaluation (ROSE), and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF). Intra-individual differences between eGFRs (eGFRdiff ) were calculated as eGFRCysC -eGFRsCr at serial time points during HF admission. We investigated associations of (i) change in eGFRdiff between baseline and day 3 or 4 with readmission-free survival up to day 60; (ii) index hospitalization length of stay (LOS) and readmission with eGFRdiff at day 60. eGFRCysC reclassified 40% of samples to more advanced kidney dysfunction. Median eGFRdiff was -4 [-11 to 1.5] mL/min/1.73 m2 at baseline, became more negative during admission and remained significantly different at day 60. The change in eGFRdiff between baseline and day 3 or 4 was associated with readmission-free survival (adjusted hazard ratio per standard deviation decrease in eGFRdiff : 1.14, P = 0.035). Longer index hospitalization LOS and readmission were associated with more negative eGFRdiff at day 60 (both P ≤ 0.026 in adjusted models). CONCLUSIONS: In acute HF, a marked difference between eGFRCysC and eGFRsCr is present at baseline, becomes more pronounced during hospitalization, and is sustained at 60 day follow-up. The change in eGFRdiff during HF admission and eGFRdiff at day 60 are associated with clinical outcomes.

Extracorporeal cardiopulmonary resuscitation in adults: evidence and implications.

Rates of survival with functional recovery for both in-hospital and out-of-hospital cardiac arrest are notably low. Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a modality to improve prognosis by augmenting perfusion to vital end-organs by utilizing extracorporeal membrane oxygenation (ECMO) during conventional CPR and stabilizing the patient for interventions aimed at reversing the aetiology of the arrest. Implementing this emergent procedure requires a substantial investment in resources, and even the most successful ECPR programs may nonetheless burden healthcare systems, clinicians, patients, and their families with unsalvageable patients supported by extracorporeal devices. Non-randomized and observational studies have repeatedly shown an association between ECPR and improved survival, versus conventional CPR, for in-hospital cardiac arrest in select patient populations. Recently, randomized controlled trials suggest benefit for ECPR over standard resuscitation, as well as the feasibility of performing such trials, in out-of-hospital cardiac arrest within highly coordinated healthcare delivery systems. Application of these data to clinical practice should be done cautiously, with outcomes likely to vary by the setting and system within which ECPR is initiated. ECPR introduces important ethical challenges, including whether it should be considered an extension of CPR, at what point it becomes sustained organ replacement therapy, and how to approach patients unable to recover or be bridged to heart replacement therapy. The economic impact of ECPR varies by health system, and has the potential to outstrip resources if used indiscriminately. Ideally, studies should include economic evaluations to inform health care systems about the cost-benefits of this therapy.

Pulmonary Embolism Response Team utilization during the COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) may predispose patients to venous thromboembolism (VTE). Limited data are available on the utilization of the Pulmonary Embolism Response Team (PERT) in the setting of the COVID-19 global pandemic. We performed a single-center study to evaluate treatment, mortality, and bleeding outcomes in patients who received PERT consultations in March and April 2020, compared to historical controls from the same period in 2019. Clinical data were abstracted from the electronic medical record. The primary study endpoints were inpatient mortality and GUSTO moderate-to-severe bleeding. The frequency of PERT utilization was nearly threefold higher during March and April 2020 (n = 74) compared to the same period in 2019 (n = 26). During the COVID-19 pandemic, there was significantly less PERT-guided invasive treatment (5.5% vs 23.1%, p = 0.02) with a numerical but not statistically significant trend toward an increase in the use of systemic fibrinolytic therapy (13.5% vs 3.9%, p = 0.3). There were nonsignificant trends toward higher in-hospital mortality or moderate-to-severe bleeding in patients receiving PERT consultations during the COVID-19 period compared to historical controls (mortality 14.9% vs 3.9%, p = 0.18 and moderate-to-severe bleeding 35.1% vs 19.2%, p = 0.13). In conclusion, PERT utilization was nearly threefold higher during the COVID-19 pandemic than during the historical control period. Among patients evaluated by PERT, in-hospital mortality or moderate-to-severe bleeding were not significantly different, despite being numerically higher, while invasive therapy was utilized less frequently during the COVID-19 pandemic.

Serial assessment of HeartMate 3 pump position and inflow angle and effects on adverse events.

OBJECTIVES: This study analyses the position of the HeartMate 3 left ventricular assist device on serial radiographs to assess positional change and possible correlation with adverse events. METHODS: We retrospectively analysed 59 left ventricular assist device recipients who had serial chest radiographs at 1 month, 6 months and 12 months post-implantation between November 2014 and June 2018. We measured pump angle, pump-spine distance and pump-diaphragm depth and investigated their relationship to a composite outcome of heart failure readmission, low flow alarms, stroke or inflow/outflow occlusion requiring surgical repositioning through recurrent event survival modelling. RESULTS: Between 1 and 6 months, the absolute pump-spine distance changed by 10.00 mm (P < 0.01) and the absolute pump-diaphragm depth changed by 18.80 mm (P < 0.01). These parameters did not change significantly between 6 and 12 months post-implantation. Pump angle did not change significantly over any period. Twenty-six patients experienced the composite outcome; in these patients, the median 1-month pump angle was 66.2° (interquartile range 54.5-78.0) as compared to 59.0° (interquartile range 47.0-65.0) in the 33 patients who did not have adverse events (P = 0.04). Pump depth and pump-spine distance at 1 month were not associated with the composite outcome. Change in pump depth between 1 and 6 months [hazard ratio (HR) 1.019; 95% confidence interval (CI) 1.000-1.039] and between 6 and 12 months (HR 1.020; 95% CI 1.000-1.040) were weakly associated with the composite outcome. CONCLUSIONS: Larger pump angles are associated with the composite outcome of position-related adverse events. Pump depth movement is weakly associated with the composite outcome.

Transition of a Large Tertiary Heart Failure Program in Response to the COVID-19 Pandemic: Changes That Will Endure.

The coronavirus disease 2019 (COVID-19) pandemic imposed severe restrictions on traditional methods of patient care. During the pandemic, the heart failure program at New York-Presbyterian Hospital in New York, NY rapidly and comprehensively transitioned its care delivery model and administrative organization to conform to a new healthcare environment while still providing high-quality care to a large cohort of patients with heart failure, heart transplantation, and left ventricular assist device. In addition to the widespread adoption of telehealth, our program restructured outpatient care, initiating a shared clinic model and introducing a comprehensive remote monitoring program to manage patients with heart failure and heart transplant. All conferences, including administrative meetings, support groups, and educational seminars were converted to teleconferencing platforms. Following the peak of COVID-19, many of the new changes have been maintained, and the program structure will be permanently altered as a lasting effect of this pandemic. In this article, we review the details of our program's transition in the face of COVID-19 and highlight the programmatic changes that will endure.

Discordance Between Clinical Assessment and Invasive Hemodynamics in Patients With Advanced Heart Failure.

BACKGROUND: Historically, invasive hemodynamic guidance was not superior compared to clinical assessment in patients admitted with acute decompensated heart failure (ADHF). This study assessed the accuracy of clinical assessment vs invasive hemodynamics in patients with ADHF. METHODS AND RESULTS: We conducted a prospective cohort study of patients admitted with ADHF. Prior to right-heart catheterization (RHC), physicians categorically predicted right atrial pressure, pulmonary capillary wedge pressure, cardiac index and hemodynamic profile (wet/dry, warm/cold) based on physical examination and clinical data evaluation (warm = cardiac index > 2.2 L/min/m2; wet = pulmonary capillary wedge pressure > 18 mmHg). We collected 218 surveys (of 83 cardiology fellows, 55 attending cardiologists, 45 residents, 35 interns) evaluating 97 patients. Of those patients, 46% were receiving inotropes prior to RHC. The positive and negative predictive values of clinical assessment compared to RHC for the cold and wet subgroups were 74.7% and 50.4%. The accuracy of categorical prediction was 43.6% for right atrial pressure, 34.4% for pulmonary capillary wedge pressure and 49.1% for cardiac index, and accuracy did not differ by clinician (P > 0.05 for all). Interprovider agreement was 44.4%. Therapeutic changes following RHC occurred in 71.1% overall (P < 0.001). CONCLUSIONS: Clinical assessment of patients with advanced heart failure presenting with ADHF has low accuracy across all training levels, with exaggerated rates of misrecognition of the most high-risk patients.

Relationship Between Noninvasive Assessment of Lung Fluid Volume and Invasively Measured Cardiac Hemodynamics.

Background Right heart catheterization is the gold standard in clinical practice for the assessment of cardiovascular hemodynamics, but it is an invasive procedure requiring expertise in both insertion and reading. Remote dielectric sensing (Re DS ) is a noninvasive electromagnetic-based technology intended to quantify lung fluid content. Methods and Results In this prospective single-center study, Re DS readings were obtained in supine position just before right heart catheterization procedure in patients with heart failure. Agreement between Re DS and pulmonary artery wedge pressure ( PAWP ) was analyzed. Of all, 139 patients with heart failure received hemodynamic assessment and Re DS measurement. A good correlation was found between Re DS and PAWP measurement ( r=0.492, P<0.001). Receiver operating characteristic analysis of the ability to identify a PAWP ≥18 mm Hg resulted in a Re DS cutoff value of 34%, with an area under the curve of 0.848, a sensitivity of 90.7%, and a specificity of 77.1%. Overall, Re DS <34% carries a high negative predictive value of 94.9%. Conclusions Lung fluid content, as measured by Re DS , correlates well with PAWP . The high sensitivity and specificity and especially the high negative predictive value make Re DS a reliable noninvasive tool at the point of care, to rule out elevated PAWP in patients with heart failure and to help with medical management of patients with heart failure. Further studies are warranted to compare this tool with existing tests and to relate the findings to the clinical outcomes.

Residual native left ventricular function optimization using quantitative 3D echocardiographic assessment of rotational mechanics in patients with left ventricular assist devices.

Preservation of native left ventricular (LV) function in patients supported with LV assist device (LVAD) may be beneficial to attain optimal hemodynamics and enhance potential recovery. Currently, LVAD speed optimization is based on hemodynamic parameters, without considering residual native LV function. We hypothesized that alternatively, LV rotational mechanics can be quantified by 3D echocardiography (3DE), and may help preserve native LV function while optimizing LVAD speed. The goal of this study was to test the feasibility of quantifying the effects of LVAD implantation on LV rotational mechanics and to determine whether conventional speed optimization maximally preserves native LV function. We studied 55 patients with LVADs, who underwent 3DE imaging and quantitative analysis of LV twist. Thirty patients were studied before and after LVAD implantation. The remaining 25 patients were studied during hemodynamic ramp studies. The pump speed at which LV twist was maximal was compared with the hemodynamics-based optimal speed. LV twist decreased following LVAD implantation from 4.2 ± 2.7 to 2.3 ± 1.9° (P < 0.01), reflecting the constricting effects on native function. With lower pump speeds, no significant changes were noted in LV twist, which peaked at a higher speed. In 11/25 (44%) patients, the conventional hemodynamic/2DE methodology and 3DE assessment of maximal residual function did not indicate the same optimal conditions, suggesting that a higher pump speed would have better preserved native function. In conclusion, quantitative 3DE analysis of LV rotational mechanics provides information, which together with hemodynamics may help select optimal pump speed, while maximally preserving native LV function.

Healthcare Resource Use and Cost Implications in the MOMENTUM 3 Long-Term Outcome Study.

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<0.001) and stroke (HM3: 2.8% versus HMII: 11.3%; 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<0.001) and similar in either bridge to transplant or destination therapy intent. 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.

Clinical implications of hemodynamic assessment during left ventricular assist device therapy.

Left ventricular assist devices (LVADs) significantly improve outcomes of advanced heart failure patients. However, patients continue to have high readmission rates due to complications ranging from bleeding, thrombosis, heart failure, and infection. Considering that the hallmark benefit of LVAD therapy is improvement in hemodynamics (cardiac unloading and increased cardiac output), hemodynamic assessment on LVAD support is key to better understand these difficult complications and may serve as a tool to resolving them. In this review, we will discuss the hemodynamic changes following LVAD implantation, and the implications and prognostic impact of hemodynamic optimization on outcomes and complications.

Left Ventricular Assist Devices for Lifelong Support.

Continuous-flow left ventricular assist devices (LVADs) have revolutionized advanced heart failure care. These compact, fully implantable heart pumps are capable of providing meaningful increases in survival, functional capacity, and quality of life. Implantation volumes continue to grow, but several challenges remain to be overcome before LVADs will be considered as the therapy of choice for all patients with advanced heart failure. They must be able to consistently extend survival for the long term (7 to 10 years), rather than the midterm (3 to 5 years) more typical of contemporary devices; they must incorporate design elements that reduce shear stress and avoid stasis to reduce the frequent adverse events of bleeding, stroke, and pump thrombosis; and they must become more cost-effective. The advancements in engineering, implantation technique, and medical management detailed in this review will highlight the progress made toward achieving lifelong LVAD support and the challenges that remain.

Cardiac Output Assessment in Patients Supported with Left Ventricular Assist Device: Discordance Between Thermodilution and Indirect Fick Cardiac Output Measurements.

Cardiac output (CO) assessed by thermodilution (TD) and indirect Fick (iFK) methods is commonly employed in left ventricular assist device (LVAD) patients; however, no study has assessed agreement. This study assesses correlation between these methods and association with hemodynamic/echocardiographic data in LVAD patients. Discordance was defined as a 20% difference between TD and iFK CO measurements. Bias and agreement were determined via the Bland-Altman technique in both the overall sample and iFK-stratified tertiles. Correlation with each assessment of CO and right heart catheterization (RHC) hemodynamics was performed. Among 111 RHCs, the mean CO for TD and iFK were 4.65 ± 1.33 (range: 1.44-9.30) and 5.37 ± 1.51 (range: 3.07-11.80) L/min (p < 0.001), respectively, with a calculated discordance of 45.9%. A correlation coefficient of 0.66 with a bias of -0.72 L/min was found. The lower and upper limit of precision were -3.12 and 1.68 L/min, respectively. By tertile analysis, bias (lower and upper limit of precision) for the low, middle, and high tertile groups were -0.24 (-1.88 and 1.40), -0.48 (-2.50 and 1.53), and -1.39 (-4.18 and 1.39) L/min, respectively. No significant correlation was found between either method with right atrial pressure or pulmonary capillary wedge pressure or any valvular condition. Substantial discrepancies exist between TD and iFK CO in LVAD patients. Although fixed bias was small, the limits of agreement extend into the clinically relevant area, with larger bias being present at higher CO. Studies with flow probes are needed to define which method better represents CO in LVAD patients.

Sequential Organ Failure Assessment Score at Presentation Predicts Survival in Patients Treated With Percutaneous Veno-Arterial Extracorporeal Membrane Oxygenation.

BACKGROUND AND PURPOSE: This study sought to investigate demographic, clinical, and procedural determinants of outcomes in patients treated with percutaneous veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) initiated in the cardiac catheterization laboratory with a portable system. METHODS: We performed a retrospective review of patients treated with percutaneous VA-ECMO during the study period at our institution. A logistic regression model was applied to investigate the association between sequential organ failure assessment (SOFA) score and survivor status. Fisher's exact test was used to examine the association between survivor status and cannula size (15 Fr vs >15 Fr). RESULTS: Percutaneous VA-ECMO was initiated in 25 patients. At 30 days, 10 patients were alive (40%). Fifteen patients had cardiac arrest (CA) prior to ECMO initiation, of which 5 were alive at 30 days (33%). Survivors had a lower baseline median SOFA score (9 vs 16; P=.02; odds ratio, 0.577). Use of a smaller cannula was associated with survival (P=.01). There was an association between the size of the arterial cannula and increased blood transfusions (P<.01). CONCLUSIONS: Lower presenting SOFA score and smaller cannula size were associated with increased survival in patients with cardiogenic shock (CS) or CA who underwent percutaneous VA-ECMO placed in the cardiac catheterization laboratory using a portable system. Calculation of the SOFA score at presentation may help physicians determine which patients may derive benefit from ECMO. Smaller cannula size, while decreasing the amount of flow, may result in decreased bleeding and increased survival.

Pre-operative mortality risk assessment in patients with continuous-flow left ventricular assist devices: application of the HeartMate II risk score.

BACKGROUND: Survival with left ventricular assist device (LVAD) therapy is dependent on appropriate patient selection. The HeartMate II risk score (HMRS) was recently derived and validated to predict 90-day mortality in clinical trial patients with continuous-flow LVADs. The aim of this study was to test HMRS validity in predicting survival at our institution. METHODS: We performed a retrospective analysis of patients implanted with HeartMate II (HMII; Thoratec, Pleasanton, CA) LVADs from March 31, 2004 to September 20, 2012 at the Columbia University Medical Center (CUMC). Patients were stratified according to HMRS profiles (HMRS Low < 1.58, 1.58 ≤ HMRS Medium ≤ 2.48, HMRS High > 2.48) calculated using age, albumin, creatinine, international normalized ratio (INR) and center volume. Outcome was defined as survival at 90 days after device implantation. RESULTS: HeartMate II LVADs were implanted in 205 patients. Pre-operative data from 201 patients were categorized into HMRS Low (n = 101; 1.04 [0.64 to 1.31]), HMRS Medium (n = 73; 1.98 [1.78 to 2.25]) and HMRS High (n = 27, 3.07 [2.70 to 3.43]) (p < 0.0001). Kaplan-Meier survival estimates at 90 days (HMRS Low 91.0 ± 2.9%, HMRS Medium 91.7 ± 3.2%, HMRS High 88.7 ± 6.1%) and at 1 year (HMRS Low 85.5 ± 3.8%, HMRS Medium 79.3 ± 5.5%, HMRS High 82.4 ± 8.4%) after LVAD implantation were not statistically different (p = 0.43). Prediction of 90-day mortality by receiver operating characteristic was poor (AUC = 0.56). CONCLUSION: HMRS stratification poorly discriminates 90-day mortality after HMII LVAD implantation at our institution. Its generalizability as a universal prognostic score may be limited.

Prevalence, significance, and management of aortic insufficiency in continuous flow left ventricular assist device recipients.

BACKGROUND: Aortic insufficiency (AI) is increasingly recognized as a complication of continuous flow left ventricular assist device support; however, its long-term prevalence, clinical significance, and efficacy of potential interventions are not well known. METHODS AND RESULTS: We studied the prevalence and management of AI in 232 patients with continuous flow left ventricular assist device at our institution. Patients with aortic valve (AV) surgery before left ventricular assist device implantation were excluded from analysis. To examine the prevalence of de novo AI, patients without preoperative AI were divided into a retrospective and a prospective cohort based on whether a dedicated speed optimization study had been performed at the time of discharge. Forty-three patients underwent AV repair at the time of implant, and 3 subsequently developed greater than mild AI. In patients without surgical AV manipulation and no AI at the time of implant, Kaplan-Meier analysis revealed that freedom from greater than mild de novo AI at 1 year was 77.6±4.2%, and that at least moderate AI is expected to develop in 37.6±13.3% after 3 years. Nonopening of the AV was strongly associated with de novo AI development in patients without prospective discharge speed optimization. Seven of 21 patients with at least moderate AI developed symptomatic heart failure requiring surgical intervention. CONCLUSIONS: AI is common in patients with continuous flow left ventricular assist devices and may lead to clinical decompensation requiring surgical correction. The prevalence of AI is substantially less in patients whose AV opens, and optimized loading conditions may reduce AI prevalence in those patients in whom AV opening cannot be achieved.

Preoperative assessment of high-risk candidates to predict survival after heart transplantation.

BACKGROUND: Alternate waiting list strategies expand listing criteria for patients awaiting heart transplantation (HTx). We retrospectively analyzed clinical events and outcome of patients listed as high-risk recipients for HTx. METHODS AND RESULTS: We analyzed 822 adult patients who underwent HTx of whom 111 patients met high-risk criteria. Clinical data were collected from medical records and outcome factors calculated for 61 characteristics. Significant factors were summarized in a prognostic score. Age >65 years (67%) and amyloidosis (19%) were the most common reasons for alternate listing. High-risk recipients were older (63.2±10.2 versus 51.4±11.8 years; P<0.001), had more renal dysfunction, prior cancer, and smoking. Survival analysis revealed lower post-HTx survival in high-risk recipients (82.2% versus 87.4% at 1-year; 59.8% versus 76.3% at 5-year post-HTx; P=0.0005). Prior cerebral vascular accident, albumin <3.5 mg/dL, re-HTx, renal dysfunction (glomerular filtration rate <40 mL/min), and >2 prior sternotomies were associated with poor survival after HTx. A prognostic risk score (CARRS [CVA, albumin, re-HTx, renal dysfunction, and sternotomies]) derived from these factors stratified survival post-HTx in high-risk (3+ points) versus low-risk (0-2 points) patients (87.9% versus 52.9% at 1-year; 65.9% versus 28.4% at 5-year post-HTx; P<0.001). Low-risk alternate patients had survival comparable with regular patients (87.9% versus 87.0% at 1-year and 65.9% versus 74.5% at 5-year post-HTx; P=0.46). CONCLUSIONS: High-risk patients had reduced survival compared with regular patients post-HTx. Among patients previously accepted for alternate donor listing, application of the CARRS score identifies patients with unacceptably high mortality after HTx and those with a survival similar to regularly listed patients.