Early elevated donor-derived cell-free DNA levels in heart transplant recipients following precision-controlled cardiac transport system or ice-cooled organ transport.

BACKGROUND: Recent innovations in temperature-controlled cardiac transportation allow for static hypothermic preservation of transplant organs during transportation. We assessed differences in donor-derived cell-free DNA (dd-cfDNA) using the SherpaPak cardiac transport system (SCTS) and traditional ice transportation. METHODS: Single-organ heart transplant recipients between January 2020 and January 2022 were included if they had dd-cfDNA measures ≤6 weeks post-transplant along with the baseline biopsy at 6 weeks as part of the surveillance protocol and no biopsy-confirmed rejection ≤90 days. Elevated dd-cfDNA ≥.20% were compared between groups using logistic regression including a subject effect. RESULTS: Of 65 hearts transplanted, 30 were transported with SCTS and 35 on ice. Recipient characteristics were similar between groups. Donors in the SCTS group were older (34 vs. 40 years, p = .04) with a longer total ischemic time (171 vs. 212 min, p = .002). Recipients in the SCTS group had a greater risk of elevated dd-cfDNA unadjusted and adjusted for donor age, and prolonged ischemic times > 3.5 h (Unadjusted odds ratio: 4.9, 95%-CI: 1.08-22.5, p = .039 and Adjusted odds ratio: 5.5, 95%-CI: 1.03-29.6, p = .046). Primary graft dysfunction rates and 1-year mortality were comparable between groups. CONCLUSION: Elevated dd-cfDNA in patients procured with SCTS may indicate that graft injury was not negated relative to ice transport. However, there were no clinical differences noted in short or long-term outcomes including mortality despite a longer ischemic time in the SCTS group.

Case report: management of refractory cardiogenic shock with Impella 5.5 in patients with transcatheter aortic valves.

Background: Impella is a transaortic valvular pump commonly utilized in patients with cardiogenic shock. However, its use with transcatheter aortic valves (TAVI) remains rare. We present two cases where surgical Impella 5.5 was placed across both Sapien 3 Ultra and Evolute Pro+ valves. Case summary: Patient 1: A 74-year-old male with history of ischaemic cardiomyopathy with ejection fraction 20-25% status post-cardiac resynchronization therapy with a defibrillator, severe aortic stenosis (AS) status post-recent Sapien 3 Ultra TAVI presented with cardiogenic shock. Due to persistent unstable haemodynamic status, Impella 5.5 was placed and was utilized as a bridge to left ventricular assist device. Patient 2: A 74-year-old male with a history of alcoholic cirrhosis and AS underwent Evolute Pro+ TAVI at outside facility. The implantation was complicated by left main coronary artery occlusion, leading to cardiogenic shock. Patient required femoral veno-arterial extracorporeal membrane oxygenation (ECMO) support and emergent single vessel coronary bypass of a saphenous venous graft to the left anterior descending artery. Extracorporeal membrane oxygenation was decannulated on Day 20 and Impella 5.5 was placed as a bridge to recovery. In both cases, there were no procedural complications or residual aortic or perivalvular regurgitation. Discussion: Impella 5.5 implanted via the axillary surgical cutdown is safe and feasible approach to manage refractory cardiogenic shock in patients with TAVI including different types of valves, Sapien 3 Ultra, and Evolute Pro+. As it can provide full haemodynamic support, Impella 5.5 can be used as bridge to recovery or durable mechanical support.

Outcomes of surgical Impella placement in acute cardiogenic shock.

Introduction: Although a role for percutaneous Impella devices has been established, there is a paucity of data regarding the utility and outcomes of larger surgically implanted Impella devices. Methods: We conducted a retrospective review of all surgical Impella implants at our institution. All Impella 5.0 and Impella 5.5 devices were included. The primary outcome was survival. Secondary outcomes included hemodynamic and end-organ perfusion as well as commonly encountered surgical complications. Results: From 2012 to 2022, 90 surgical Impella devices were implanted. The median age was 63 [53-70] years, the mean creatinine was 2.07 ± 1.22 mg/dL, and the average lactate level was 3.32 ± 2.90 mmol/L. Prior to implantation, 47 patients (52%) were supported with vasoactive agents, while 43 (48%) were also supported with another device. The most common etiology of shock was acute on chronic heart failure (50, 56%), followed by acute myocardial infarction (22, 24%), and postcardiotomy (17, 19%). Overall, 69 patients (77%) survived to device removal, and 57 (65%) survived to hospital discharge. One-year survival was 54%. Neither etiology of heart failure nor device strategy was associated with 30-day or 1-year survival. On multivariable modeling, the number of vasoactive medications prior to device implantation was strongly associated with 30-day mortality (hazard ratio 1.94 [1.27-2.96], P < 0.01). Surgical Impella placement was associated with a significant decreased need for vasoactive infusions (P < 0.01) and decreased acidosis (P = 0.01). Conclusions: Surgical Impella support for patients in acute cardiogenic shock is associated with lower vasoactive medication use, improved hemodynamics, increased end-organ perfusion, and acceptable morbidity and mortality.

Managing Right Ventricular Failure After Left Ventricular Assist Device Implant at a Destination Therapy Center.

Although left ventricular assist device (LVAD) implant is associated with an increased survival in patients with end-stage heart failure, severe right ventricular failure requiring a right ventricular assist device (RVAD) placement is associated with increased short-term morbidity and mortality. Patients not eligible for transplant have limited options, which may impact decision-making and outcomes at nontransplant centers. We conducted a retrospective review of all LVAD implants at our nontransplant center. Primary stratification was by the need for a postoperative RVAD implant. The primary outcome was survival. The Cox proportional hazards regression modeling was used to further evaluate mortality. From 2017 to 2022, 128 patients underwent a primary LVAD implant and 24 (18.75%) required a perioperative RVAD placement. RVAD implant was associated with increased operative mortality (1.92% vs 33.33%, p <0.01) and decreased 1-year (91.29% vs 60.60%, p <0.01) and 2-year survival (84.05% vs 36.36%, p <0.01). However, in patients who survived their index hospitalization, 1-year (93.00% vs 91.67%, p = 0.78) and 2-year (86.16% vs 55.00%, p = 0.10) mortality were similar. On multivariable analysis, the need for a RVAD was associated with an increased hazard of 1-year (5.60 [1.96 to 16.01], p <0.01) and 2-year (5.17 [2.01 to 13.28], p <0.01) mortality. In conclusion, our series from a nontransplant center suggests that patients who survive the implant have acceptable short-term survival, even if they do not have a transplant option; thus, carefully selected patients with biventricular failure may benefit from an LVAD implant, even if an RVAD is needed.

Extracorporeal membrane oxygenation for large pulmonary emboli.

Massive and submassive pulmonary emboli (PE) are increasingly being treated with percutaneous lytic and embolectomy procedures. While these procedures are overwhelmingly safe, patients with significant right ventricular strain are at risk for hemodynamic compromise requiring extracorporeal membrane oxygenation (ECMO). We conducted a retrospective study of all patients requiring ECMO support for PE from 2014 through 2022. The primary outcome was survival. Secondary outcomes included commonly encountered ECMO complications. From 2014 to 2022, 10 patients with submassive or massive PE required ECMO support. All 10 patients (100%) had right ventricular strain on echocardiography, 7 (70%) had a saddle PE, and 3 (30%) had extensive bilateral PE. Six (60%) patients required cardiopulmonary resuscitation prior to ECMO cannulation, and 4 (40%) were undergoing cardiopulmonary resuscitation while being cannulated. Nine (90%) patients were placed on venoarterial ECMO through the femoral vessels, while 1 (10%) was cannulated with right atrial to pulmonary artery ECMO. The median duration of support was 4 [3-8] days. During their course, 5 patients underwent percutaneous embolectomy, 1 underwent surgical embolectomy, and 4 underwent percutaneous lytic therapy. All patients (100%) survived to ECMO decannulation, and 6 (60%) survived to discharge. With a mean follow-up of 496 days, there were no postdischarge mortalities. In conclusion, although therapy for large PE is well tolerated, a small number of patients will experience periprocedural hemodynamic collapse requiring ECMO support. ECMO for PE patients is associated with acceptable morbidity and mortality. Further investigation is warranted to better characterize which patients are likely to require ECMO support.

Safety and efficacy of ProtekDuo right ventricular assist device: A systemic review.

BACKGROUND: Right ventricular failure is associated with increased morbidity and mortality. The ProtekDuo (Livanova, Uk) is a dual-lumen cannula that allows for percutaneous right ventricular support and may be connected to a centrifugal blood pump such as the TandemHeart or LifeSparc (Livanova, UK). This systematic review aims to evaluate the safety and efficacy of ProtekDuo right ventricular support and evaluate potential clinical variables that can influence outcomes. METHODS: PubMed, MEDLINE, SCOPUS, EMBASE, and the Cochrane Library were systematically searched. Studies meeting inclusion criteria, where ProtekDuo was used as the right ventricular assist device with reported numerical death counts for mortality as outcome measures. The primary endpoints were in-hospital 30-day and 1-year mortality rates. Secondary endpoints included ICU length of stay, conversion rates to surgical RVADs, ProtekDuo wean rates, duration of use of ProtekDuo, and adverse event rates. RESULTS: Of 49 studies reviewed, 7 met inclusion criteria with study periods between October 2014 and November 2019. ProtekDuo was utilized due to RV failure post-LVAD insertion in 64.8% (68/105) of patients. In-hospital mortality, 30-day mortality, and 1-year mortality ranged between 9%-46%, 15%-40%, and 19%-40%, respectively. Weaning from ProtekDuo and conversion to surgical RVAD ranged between 24%-91% and 11%-35%, respectively. The ICU stay average ranged from 15.8 to 36 days and ProtekDuo mean support duration ranged from 10.5 to 58 days. CONCLUSION: The ProtekDuo cannula is increasingly utilized as a right ventricular support device. Despite the sparse retrospective data available with variable patient characteristics and study design, percutaneous RV mechanical support via ProtekDuo cannula is a safe and feasible option.

Impella 5.5 and venovenous extracorporeal membrane oxygenation as a bridge to ventricular assist device in cardiopulmonary failure.

Venoarterial extracorporeal membrane oxygenation (ECMO) in the setting of combined cardiopulmonary failure provides full support of both cardiac and respiratory systems. However, it is difficult to isolate and evaluate pulmonary recovery independent of cardiac function on venoarterial ECMO. In this case report, we demonstrate the advantage of supporting a patient in cardiopulmonary failure with venovenous ECMO and the Impella 5.5 as a method to isolate organ dysfunction, wean off ECMO as respiratory function improves, and bridge to a left ventricular assist device with Impella 5.5 monotherapy.

The Impact of MOMENTUM 3 Trial Eligibility on Left Ventricular Assist Device Outcomes: A Real-World Experience.

INTRODUCTION: Although the landmark MOMENTUM 3 trial was associated with excellent short-term left ventricular assist device (LVAD) outcomes, many end-stage heart failure patients would not have met the trial eligibility criteria. Moreover, the outcomes of trial ineligible patients are poorly characterized. Therefore, we undertook this study to compare MOMENTUM 3 eligible and ineligible patients. METHODS: We conducted a retrospective review of all primary LVAD implants from 2017 to 2022. Primary stratification was according to MOMENTUM 3 inclusion and exclusion criteria. Primary outcome was survival. Secondary outcomes included complications and length of stay. Multivariable Cox proportional hazards regression models were constructed to further characterize outcomes. RESULTS: From 2017 to 2022, 96 patients underwent primary LVAD implantation. Thirty-seven (38.54%) patients were trial eligible while 59 (61.46%) were ineligible. When stratified by trial eligibility, patients who were trial eligible had higher 1-year (80.15% versus 94.52%, P = 0.04) and 2-year survival (70.17% versus 94.52%, P = 0.02). Multivariable analysis showed that trial eligibility was protective of mortality at both 1 y (HR: 0.19 [0.04-0.99], P = 0.049) and 2 y (HR: 0.17 [0.03-0.81], P = 0.03). Although the groups had similar rates of bleeding, stroke, and right ventricular failure, trial ineligibility was associated with a longer periprocedural length of stay. CONCLUSIONS: In conclusion, the majority of contemporary LVAD patients would not have been eligible for the MOMENTUM 3 trial. Ineligible patients have decreased but acceptable short-term survival. Our findings suggest that a simply reductionist approach to short-term mortality may improve outcomes but fail to capture the majority of patients who could benefit from therapy.

The Utility of Home Sleep Apnea Testing in the Advanced Heart Failure Populations.

Untreated sleep disorders form a risk of coronary artery disease, hypertension, obesity, and diabetes mellitus. Access to polysomnography is limited, especially during the COVID-19 pandemic, with home sleep apnea testing (HSAT) being a potentially viable alternative. We describe an HSAT protocol in patients with advanced heart failure (HF). In a single-center, observational analysis between 2019 and 2021 in patients with advanced HF and heart transplant (HT), 135 screened positive on the STOP-Bang sleep survey and underwent a validated HSAT (WatchPAT, ZOLL-Itamar). HSAT was successful in 123 patients (97.6%), of whom 112 (91.1%; 84 HF and 28 HT) tested positive for sleep apnea. A total of 91% of sleep apnea cases were obstructive, and 63% were moderate to severe. Multivariable linear regression showed that the apnea hypopnea index was 34% lower in the HT group than in the HF group (p = 0.046) after adjusting for gender, and that this effect persisted in White patients but not among African-Americans. Patient characteristics were similar between groups, with coronary artery disease, diabetes mellitus, and hypertension as the most prevalent co-morbidities. In conclusion, sleep apnea remains prevalent in patients with HF with a high co-morbidity burden. HSAT is a feasible and effective tool for screening and diagnosis in this population.

Elderly Patients With Higher Acuity Have Similar Left Ventricular Assist Device Outcomes as Younger Patients at a Nontransplant Center.

Although left ventricular assist device (LVAD) implantation is associated with acceptable survival, previous reports have demonstrated that advanced age is associated with increased short-term mortality. Because age is a relative contraindication to transplantation, nontransplant centers tend to implant a disproportionate number of elderly patients. We undertook this study to evaluate the impact of advanced age on LVAD outcomes at a nontransplant center. We conducted a retrospective review of all LVAD implants at our center from 2017 to 2022. Primary stratification was by age >70 years. The primary outcome was survival as assessed by the Kaplan-Meier method. The risk of 1-year mortality was further evaluated using multivariable Cox proportional hazards regression modeling. From 2017 to 2022, 93 patients underwent LVAD implantation. The mean age was 65.03 ± 11.28 years, with a median age of 68 (60 to 73) years. Most patients were INTERMACS 1 or 2 (71 patients; 76.34%). When stratified by age, 41 patients (44.09%) were aged ≥70 years. Patients aged ≥70 years had similar 30-day (96.15% vs 100.00%, p = 0.213), 1-year (90.05% vs 84.00%, p = 0.444), and 2-year survival (82.03% vs 84.00%, p = 0.870). When only the INTERMACS 1 and 2 patients with higher acuity were included, there was still no difference in 30-day, 1-year, or 2-year survival. On multivariable analysis, age >70 years was not associated with an increased hazard of 1-year mortality (0.90 [0.22 to 3.67], p = 0.878). In conclusion, in carefully selected patients, age >70 years is not associated with increased short-term mortality. Age alone should not be a contraindication to LVAD therapy.

Novel Estimates of Renal Function are Associated with Short-Term Left Ventricular Assist Device Outcomes.

INTRODUCTION: Although preoperative kidney function has been associated with left ventricular assist device (LVAD) outcomes, most previous estimates of glomerular filtration rates (eGFRs) have utilized race in the calculation. Recently, novel eGFR equations independent of race have been suggested and validated. Therefore, we undertook this study to evaluate the predictive value of a novel, non-race-based eGFR calculation on short-term LVAD outcomes. METHODS: We conducted a retrospective review of all primary LVAD implants from 2017 to 2022 at our institution. eGFR was calculated using the novel Chronic Kidney Disease Epidemiology Collaboration 2021 formula (CKD-EPI 2021). eGFR was also calculated according to the Modification of Diet in Renal Disease equation for historical reference. Primary stratification was by eGFR: ≥60, 30-60, and <30. The primary outcome was 1-y survival. Multivariable Cox proportional hazards regression modeling was used to further evaluate the impact of kidney function on 1-y mortality. RESULTS: From 2017 to 2022, 91 patients underwent LVAD implantation with a HeartMate 3 device. The average age was 65.20 ± 11.08, 77 (84.62%) were male, and 14 (15.38%) were Black. The mean CKD-EPI 2021 eGFR was 56.07 ± 23.55 compared with 54.72 ± 26.37 as calculated by Modification of Diet in Renal Disease (P = 0.719). Overall, 30-d and 1-y survival was 96.7% and 85.0%, respectively. When stratified by eGFR, there was a significant difference in 1-y survival (≥60, 93.46%; 30-60, 87.36%; <30, 62.75%; P = 0.016). On multivariable analysis, a preoperative eGFR <30 was associated with an increased hazard of 1-y mortality (5.58 [1.06-29.17], P = 0.043). CONCLUSIONS: In conclusion, non-race-based estimates of renal function are predictive of short-term LVAD outcomes. Further investigation of this phenomenon is warranted.

Temporary Right Ventricular Assist Device Support for Acute Right Heart Failure: A Single-Center Experience.

INTRODUCTION: Severe right ventricular (RV) failure is associated with significant morbidity and mortality. Although right ventricular assist devices (RVADs) are increasingly used for refractory RV failure, there is limited data on their short- and long-term outcomes. Therefore, we undertook this study to better understand our experience with temporary RVADs. METHODS: We conducted a retrospective review of all RVADS performed from 2017 to 2021. Patients supported with surgical RVADs, the Protek Duo device, and the Impella RP device were included. Patients were stratified by the type of RVAD and by etiology of RV failure. Survival was assessed by the Kaplan-Meier method and multivariable Cox proportional hazards regression models. RESULTS: From 2017 to 2021, 42 patients underwent RVAD implantation: 32 with a Protek Duo, 6 with an Impella RP, and 4 with a surgical RVAD. Majority of patients were already supported with an alternate form of mechanical support. Most patients had impaired renal function, decreased hepatic function, and lactic acidosis at the time of cannulation. The median duration of RVAD support was 8.5 [5-19] d. Survival to decannulation was 68.4%, to discharge was 47.4%, and to 1-y was 40.2%. Multivariable analysis identified elevated total bilirubin levels to be associated with 30-d mortality while increased hemoglobin levels were protective. After RVAD cannulation, the median number of pressors and inotropes was lower (P < 0.01) and the lactic acidosis was less (P < 0.01). CONCLUSIONS: In conclusion, RVAD support is associated with lower lactate levels, and decreased number of vasoactive medications, but is associated with significant morbidity and mortality.

Impact of Preoperative Liver Function on Short-Term HeartMate 3 Outcomes.

Although left ventricular assist device (LVAD) therapy is associated with improved survival, the impact of preoperative liver function on short-term outcomes is unclear. We conducted a retrospective review of all primary HeartMate 3 LVAD implants at a single center. Composite metrics of hepatic function including the model for end-stage liver disease (MELD), the MELD with sodium, and the MELD excluding international normalized ratio (MELD-XI) were evaluated. Receiver operator characteristic curves were compared to determine which equation was most predictive of 1-year survival. Primary stratification was based on MELD-XI tertiles. Secondary stratification was based on hypoalbuminemia (<3.0 mg/100 ml). A total of 94 patients underwent primary LVAD implantation from 2017 to 2022. MELD-XI and hypoalbuminemia were most associated with 1-year outcomes. When stratified by MELD tertiles, higher MELD was strongly associated with decreased 30 days (100.00% vs 100.00% vs 90.32%, p = 0.04), 1-year (93.00% vs 93.32% vs 69.79%, p = 0.01), and 2-year survival (93.00% vs 83.21% vs 69.79%, p = 0.04). In addition, while hypoalbuminemia was associated with similar 30 days (97.87% vs 95.74%, p = 0.56) survival, it was associated with a significant decrease in 1-year (92.93% vs 77.92%, p = 0.03) and 2-year survival (92.93% vs 68.89%, p <0.01). These results persisted on multivariable analysis for both MELD-XI score (p = 0.04) and hypoalbuminemia (p = 0.04). In conclusion, this is the first study to demonstrate that preoperative MELD-XI score and serum albumin levels are associated with short-term HeartMate 3 outcomes.

Impact of preoperative Impella support on destination left ventricular assist device outcomes.

BACKGROUND: Although left ventricular assist device (LVAD) implantation is associated with improved heart failure survival, the impact of pre-implantation Impella support on outcomes is unknown. We undertook this study to evaluate the impact of preoperative Impella support on LVAD outcomes. METHODS: We conducted a retrospective review of all Heartmate 3 LVAD implants. Primary stratification was by the need for preoperative Impella support with the 5.0/5.5 device. Longitudinal survival was assessed by the Kaplan-Meier method. Multivariable Cox proportional hazards regression models were developed to evaluate mortality. Secondary outcomes included changes in laboratory values during Impella support. RESULTS: From 2017 to 2021, 87 patients underwent LVAD implantation. Sixteen were supported with a single inotrope, 36 with dual inotropes, 27 with Impella, and 3 with extracorporeal membrane oxygenation (ECMO). When stratified by the need for Impella, there was no difference in survival at 30-days (98.3 [88.2-99.8]% vs. 96.3 [76.5-99.5]%, p = .59), 1-year (91.0 [79.8-96.2] vs. 74.9 [51.7-88.2], p = .10), or at 2 years (87.9 [74.3-94.5] vs. 74.9 [51.7-88.2], p = .15). On multivariable modeling, the need for preoperative Impella was not associated with an increased hazard of 1-year (1.24 [0.23-6.73], p = .81) or 2-year mortality (1.05 [0.21-5.19], p = .95). After 7 (5-10) days of Impella support, recipient creatinine (p < .01), creatinine clearance (p = .02), and total bilirubin (p = .053) improved and lactic acidosis resolved (p < .01). CONCLUSIONS: Preoperative Impella support is not associated with increased short or long-term mortality but is associated with improved renal and hepatic function as well as total body perfusion before LVAD implantation.

Development of a non-transplant left ventricular assist device program.

INTRODUCTION: Although the established long-term benefit of left ventricular assist device (LVAD) therapy has led to its proliferation as destination therapy (DT), few studies have evaluated LVAD outcomes at nontransplant centers. We undertook this study to better evaluate our experience in building a nontransplant, DT LVAD program. METHODS: We conducted a retrospective review of all LVADs implanted from 2010 to 2021. Patient, operative, and outcome data were extracted from the electronic medical record. Secular trends were evaluated by organizing the data into eras of implant. Survival was assessed using the Kaplan-Meier method. Multivariable Cox proportional hazards regression models further evaluated outcomes. RESULTS: From 2010 to 2021, 100 primary LVAD implants were performed. Annual volume grew from 1 to 30 implants per year. The average age of our cohort was 65.7 years, most patients (80%) were male, 51% had an ischemic etiology, and 65 (65%) were INTERMACS profile 1 or 2. Our 1- and 2-year survival were 82% and 79%, respectively. Multivariable analysis of 1-year mortality demonstrated that decreasing renal function and increased cardiopulmonary bypass (CPB) time were associated with increased mortality while preoperative hemoglobin was protective. When stratified by era of implant, our most recent patients were more likely to be INTERMACS profile 1 or 2; had shorter CPB and aortic cross clamp times; required fewer reoperations for bleeding; and suffered less right ventricular failure requiring mechanical support. CONCLUSIONS: A single, nontransplant LVAD center can experience significant growth in volume in a high-acuity cohort while maintaining acceptable outcomes and quality of care.

Trends in Hospital Admissions for Systolic and Diastolic Heart Failure in the United States Between 2004 and 2017.

Heart failure (HF) affects 6 million people in the United States and costs $30 billion annually. It is unclear whether improvements in length of stay and mortality over the last few decades hold true for both systolic and diastolic HF. To better assess the epidemiological and economic burden of HF, we assessed the trends in outcomes and costs for both systolic and diastolic HF. We identified hospitalizations for systolic and diastolic HF in the National Inpatient Sample database and evaluated trends over the period from 2004 to 2017, adjusting for demographics and co-morbidities. The proportion of patients admitted with an exacerbation of systolic HF increased from 42% to 63% over the study period. We found an overall decreasing trend between 2004 and 2011 in the length of stay for HF in general with a sharper decrease in diastolic than systolic HF. Inpatient mortality decreased between 2004 and 2007 and stabilized between 2008 and 2016. Systolic HF was associated with higher mortality than diastolic HF. The total inflation-adjusted cost did not change significantly over the study period, with systolic HF costing, on average, $3,036 more than diastolic HF per admission. In conclusion, systolic HF overtook diastolic HF, accounting for most HF hospitalizations in 2008. The higher hospitalization costs for systolic HF relative to diastolic HF may have resulted, in part, from greater use of advanced support devices in patients with systolic HF.

Observed elevated donor-derived cell free DNA in orthotopic heart transplant recipients without clinical evidence of rejection.

Donor-derived cell free DNA (dd-cfDNA) has rapidly become part of rejection surveillance following orthotopic heart transplantation. However, some patients show elevated dd-cfDNA without clinical evidence of rejection. With the aim to provide a clinical description of this subpopulation, we retrospectively analyzed 35 cardiac transplant recipients at our center who experienced elevated (≥.20%) dd-cfDNA in the absence of clinical rejection, out of a total 106 recipients who had dd-cfDNA results available during the first year. The median time to first elevated dd-cfDNA level was 46 days, and the highest dd-cfDNA recorded within 1 year was .31% [inter-quartile range, .23-.45]. Twenty-two (63%) patients experienced infections (cytomegalovirus (CMV) or other), and 16 (46%) presented with de novo donor-specific antibodies. Cluster analysis revealed four distinct groups characterized by (a) subclinical rejection with 50% CMV (n = 16), (b) non-CMV infections and the longest time to first elevated dd-cfDNA (187 days) (n = 8), (c) right ventricular dysfunction (n = 6), and (d) women who showed the youngest median age (45 years) and highest median dd-cfDNA (.50%) (n = 5). Continued prospective analysis is needed to determine if these observations warrant changes in patient management to optimize the utilization of this vital non-invasive graft surveillance tool.