Search

BACKGROUND: A better understanding is needed of the burdens and benefits of left ventricular assist device (LVAD) implantation on patients’ physical, mental, and social well-being. The purpose of this report was to evaluate the validity of Patient-Reported Outcomes Measurement Information System (PROMIS) measures for LVAD patients and to estimate clinically important score differences likely to have implications for patient treatment or care. METHODS: Adults from 12 sites across all US geographic regions completed PROMIS measures ≥3 months post-LVAD implantation. Other patient-reported outcomes (eg, Kansas City Cardiomyopathy Questionnaire-12 item), clinician ratings, performance tests, and clinical adverse events were used as validity indicators. Criterion and construct validity and clinically important differences were estimated with Pearson correlations, ANOVA methods, and Cohen d effect sizes. RESULTS: Participants’ (n=648) mean age was 58 years, and the majority were men (78%), non-Hispanic White people (68%), with dilated cardiomyopathy (55%), long-term implantation strategy (57%), and New York Heart Association classes I and II (54%). Most correlations between validity indicators and PROMIS measures were medium to large (≥0.3; p CONCLUSIONS: The findings provide convincing evidence for the relevance and validity of PROMIS physical, mental, and social health measures in patients from early-to-late post-LVAD implantation. Findings may inform shared decision-making when patients consider treatment options. Patients with an LVAD, their caregivers, and their clinicians should find it useful to interpret the meaning of their PROMIS scores in relation to the general population, that is, PROMIS may help to monitor a return to normalcy in everyday life. REGISTRATION: URL: https://clinicaltrials.gov ; Unique: identifier: NCT03044535.

The authors sought to examine the long-term cognitive outcome of patients with continuous flow left ventricular assist device (CF-LVAD).Data on long-term neurocognitive outcome in LVAD are limited. We examined the neurocognitive outcome of patients who received a CF-LVAD as destination therapy.Patients with HeartWare (HVAD) and HeartMate II who were enrolled in the ENDURANCE and ENDURANCE Supplemental trials were eligible. Cognition was evaluated with neuropsychological testing preoperatively and at 6, 12, and 24 months after implantation. General linear models identified demographic, disease, and treatment factors that predicted decline on each neurocognitive measure.Of 668 patients who completed baseline testing and at least 1 follow-up evaluation, 552 were impaired at baseline on at least 1 cognitive measure. At each follow-up, approximately 23% of tested patients declined and 20% improved relative to baseline on at least 1 cognitive measure. Of those who were intact at baseline, only 10%-12% declined in delayed memory and 11%-16% declined in executive function at all 3 follow-ups. For patients impaired at baseline, delayed memory decline was associated with the HVAD device and male sex, whereas executive function decline was associated with the HVAD device and stroke during CF-LVAD support. For patients intact at baseline, male sex and history of hypertension were associated with decline in immediate memory and executive function, respectively.Neurocognitive function remained stable or improved for most patients (∼80%) with CF-LVAD at 6, 12, and 24 months after implantation. Male sex, hypertension, HVAD, and stroke were associated with cognitive decline.

Background: Ventricular assist device (VAD) patients are at high risk for morbidities and mortality. One potentially beneficial component of the Joint Commission VAD Certification process is the requirement that individual VAD programs select 4 performance measures to improve and optimize patients’ clinical outcomes. Problem Statement: Review of patient data after our program’s first certification visit in 2008 showed that, compared to national recommendations and published reports, our patients had suboptimal outcomes in 4 areas after device implantation: length of hospital stay, receipt of early (Methods: Plan-Do-Study-Act processes were implemented to shorten length of stay, increase patient receipt of early physical therapy, decrease driveline infection incidence, and improve nutritional status. With 2008 as our baseline, we deployed interventions for each outcome area across 2009 to 2017. Performance improvement activities included staff, patient, and family didactic, one-on-one, and hands-on education; procedural changes; and outcomes monitoring with feedback to staff on progress. Descriptive and inferential statistics were examined to document change in the outcomes. Outcomes: Across the performance improvement period, length of stay decreased from 40 to 23 days; physical therapy consults increased from 87% to 100% of patients; 1-year driveline infection incidence went from 38% to 23.5%; and the percentage of patients with prealbumin within the normal range increased from 84% to 90%. Implications: Performance improvement interventions may enhance ventricular assist device patient outcomes. Interventions’ sustainability should be evaluated to ensure that gains are not lost over time.

Stroke is a devastating morbidity associated with left ventricular assist device (LVAD) support. We report a comprehensive analysis of stroke subtypes in the ENDURANCE destination therapy (DT) and ENDURANCE Supplemental (DT2) trials.Patients in the combined HeartWare LVAD (HVAD) cohorts of the DT and DT2 trials were included. Neurologic events included ischemic stroke (ischemic cerebrovascular accident [ICVA]), hemorrhagic stroke (hemorrhagic cerebrovascular accident [HCVA]), and transient ischemic attack (TIA). Peri-operative strokes were defined as occurring within 2 weeks of the implant.A total of 604 patients received an HVAD in the DT (n = 296) and DT2 (n = 308) trials. Over 2 years, 178 (29.5%) had at least 1 cerebrovascular accident (CVA). Forty-four (7.3%) had HCVAs, 116 (19.2%) had ICVAs, and 44 (7.3%) had TIAs. Thirty (5.0%) had peri-operative stroke. In multivariable analysis, sub-therapeutic international normalized ratio (INR) values were independently associated with peri-operative stroke. Supra- and/or sub-therapeutic INR values, peripheral vascular disease, and presence of left ventricular thrombus were independently associated with ICVA. No aspirin and supra- and/or sub-therapeutic INR values were independently associated with TIA. No aspirin, supra- and/or sub-therapeutic INR values, and prior stroke and/or TIA were associated with HCVA. In further analysis, mean arterial pressure (MAP) was higher in the ICVA (86.8mm Hg, p = 0.002 4) and TIA (88.8mm Hg, p0.0001) groups, but not in HCVA, than in the No-CVA group (81.4mm Hg). Time in therapeutic range for INR was 65.3% for the No-CVA group, 62.9% (p = 0.59) for HCVA, 65.1% (p = 0.97) for ICVA, and 63.2% (p = 0.62) for TIA.Supra- and sub-therapeutic INR values at the time of CVA were associated with all stroke subtypes14 days post-implant. MAP was higher among those with ICVA and TIA but not with HCVA compared to without CVA. Our study demonstrates the challenges of anti-thrombotic therapy and blood pressure management in LVAD population.

Current risk stratification models to predict outcomes after a left ventricular assist device (LVAD) are limited in scope. We assessed the performance of Bayesian models to stratify post-LVAD mortality across various International Registry for Mechanically Assisted Circulatory Support (INTERMACS or IM) Profiles, device types, and implant strategies. We performed a retrospective analysis of 10,206 LVAD patients recorded in the IM registry from 2012 to 2016. Using derived Bayesian algorithms from 8,222 patients (derivation cohort), we applied the risk-prediction algorithms to the remaining 2,055 patients (validation cohort). Risk of mortality was assessed at 1, 3, and 12 months post implant according to disease severity (IM profiles), device type (axial versus centrifugal) and strategy (bridge to transplantation or destination therapy). Fifteen percentage (n = 308) were categorized as IM profile 1, 36% (n = 752) as profile 2, 33% (n = 672) as profile 3, and 15% (n = 311) as profile 4-7 in the validation cohort. The Bayesian algorithms showed good discrimination for both short-term (1 and 3 months) and long-term (1 year) mortality for patients with severe HF (Profiles 1-3), with the receiver operating characteristic area under the curve (AUC) between 0.63 and 0.74. The algorithms performed reasonably well in both axial and centrifugal devices (AUC, 0.68-0.74), as well as bridge to transplantation or destination therapy indication (AUC, 0.66-0.73). The performance of the Bayesian models at 1 year was superior to the existing risk models. Bayesian algorithms allow for risk stratification after LVAD implantation across different IM profiles, device types, and implant strategies.

The risk of infection after heart transplantation is highest within the first year and represents the leading cause of early mortality. In this cohort of patients enrolled in the Outcomes AlloMap Registry (OAR), we sought to describe infection episodes (IEp) resulting in hospitalization, in the early (1 year) and late (≥1 year) post-transplant period and determine the impact of immunosuppression on incidence of infection.The primary aim was to assess the incidence and nature of IEp. The secondary aim was to evaluate the effect of potential risk factors, such as recipient age; sex; body mass index; panel-reactive antibodies; cytomegalovirus (CMV) primary mismatch; prednisone, tacrolimus, and sirolimus levels; and gene expression profile (GEP) score, in the development of IEp.The OAR comprises 1,504 patients, of whom 220 patients (14.6%) had an IEp during a median follow-up period of 382 days (interquartile range [IQR] 230 to 579 days). The cause-specific 5-year hazard ratio for any infection was 2.029 (p = 0.12). The pattern of early infection was consistent with nosocomial and opportunistic causes, whereas later infection was consistent with late-onset opportunistic and community-acquired etiologies. Sixty-two percent of the infections occurred early. In the time-dependent analysis, higher prednisone dose (log prednisone, hazard ratio [HR] 1.30, p = 0.022) was the most significant risk factor for all IEp.In the OAR cohort, the majority of infections occurred within 1 year after transplantation. Clinicians may consider more aggressive prednisone withdrawal in low-risk patients to reduce IEp.

BACKGROUND Some literature exists potentially linking proliferation signal inhibitors (PSIs) to venous thromboembolism (VTE). We sought to determine the impact of PSIs on development of VTE in heart transplant (HT) patients while controlling for other risk factors. METHODS The incidence and predisposing factors of VTE were analyzed in this retrospective review of patients >18 years who underwent HT January 2000 to October 2016. Re-transplants, multiorgan transplants, or patients that expired within 30 days post-HT were excluded. VTE incidence rates are reported as number of events per 100 person-years. Cox proportional hazards models were used to assess the relationship between PSI exposure (time-varying covariate) and VTE. RESULTS Of 561 HT recipients, 112 received PSIs, started a median of 1.5 years post-HT. There were 102 total VTE events: 78 in PSI-naive patients during 2,547 patient-years (3.0 events per 100 person-years) vs 24 in PSI-exposed patients during 544 patient-years (4.4 events per 100 person-years). Cox proportional hazards models with PSI exposure as a time-varying covariate indicated the increased risk was statistically significant (unadjusted hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.31 to 3.49, p = 0.002). A VTE history was significantly associated with increased risk of VTE post-HT (HR 1.58, 95% CI 1.07 to 2.35, p = 0.022); however, the risk remained significant when adjusting for potential confounders, including previous VTE (HR 2.0, 95% CI 1.18 to 3.38, p = 0.010). CONCLUSIONS Exposure to PSIs is associated with a significant increase in risk for VTE even when controlling for other risk factors. When considering the use of PSI-based immunosuppression after HT, the risk of VTE over time should be weighed against the potential benefit.

BACKGROUND The outlook for ambulatory patients with advanced heart failure (HF) and the appropriate timing for left ventricular assist device (LVAD) or transplant remain uncertain. The aim of this study was to better understand disease trajectory and rates of progression to subsequent LVAD therapy and transplant in ambulatory advanced HF. METHODS See Related Editorial, page XXX Patients with advanced HF who were New York Heart Association (NYHA) Class III or IV and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profiles 4 to 7, despite optimal medical therapy (without inotropic therapy), were enrolled across 11 centers and followed for the end-points of survival, transplantation , LVAD placement, and health-related quality of life. A secondary intention-to-treat survival analysis compared outcomes for MedaMACS patients with a matched group of Profile 4 to 7 patients with LVADs from the INTERMACS registry. RESULTS Between May 2013 and October 2015, 161 patients were enrolled with INTERMACS Profiles 4 (12%), 5 (32%), 6 (49%), and 7 (7%). By 2 years after enrollment, 75 (47%) patients had reached a primary end-point with 39 (24%) deaths, 17 (11%) undergoing LVAD implantation, and 19 (12%) receiving a transplant. Compared with 1,753 patients with Profiles 4 to 7 receiving LVAD therapy, there was no overall difference in intention-to-treat survival between medical and LVAD therapy, but survival with LVAD therapy was superior to medical therapy among Profile 4 and 5 patients (p = 0.0092). Baseline health-related quality of life was lower among patients receiving a LVAD than those enrolled on continuing oral medical therapy, but increased after 1 year for survivors in both cohorts. CONCLUSIONS Ambulatory patients with advanced HF are at high risk for poor outcomes, with only 53% alive on medical therapy after 2 years of follow-up. Survival was similar for medical and LVAD therapy in the overall cohort, which included the lower severity Profiles 6 and 7, but survival was better with LVAD therapy among patients in Profiles 4 and 5. Given the poor outcomes in this group of advanced HF patients, timely consideration of transplant and LVAD is of critical importance.

Right heart failure (RHF) after left ventricular assist device (LVAD) implantation is associated with high morbidity and mortality. Existing risk scores include semiquantitative evaluation of right ventricular (RV) dysfunction. This study aimed to determine whether quantitative evaluation of both RV size and function improve risk stratification for RHF after LVAD implantation beyond validated scores.From 2009 to 2015, 158 patients who underwent implantation of continuous-flow devices who had complete echocardiographic and hemodynamic data were included. Quantitative RV parameters included RV end-diastolic (RVEDAI) and end-systolic area index, RV free-wall longitudinal strain (RVLS), fractional area change, tricuspid annular plane systolic excursion, and right atrial area and pressure. Independent correlates of early RHF (30 days) were determined with the use of logistic regression analysis. Mean age was 56 ± 13 years, with 79% male; 49% had INTERMACS profiles ≤2. RHF occurred in 60 patients (38%), with 20 (13%) requiring right ventricular assist device. On multivariate analysis, INTERMACS profiles (adjusted odds ratio 2.38 [95% confidence interval [CI] 1.47-3.85]), RVEDAI (1.61 [1.08-2.32]), and RVLS (2.72 [1.65-4.51]) were independent correlates of RHF (all P.05). Both RVLS and RVEDAI were incremental to validated risk scores (including the EUROMACS score) for early RHF after LVAD (all P.01).RV end-diastolic and strain are complementary prognostic markers of RHF after LVAD implantation.

Background The advent of direct-acting antiviral therapy for Hepatitis C (HCV) has made using HCV-viremic donors a viable strategy to address the donor shortage in heart transplantation . We employed a large-scale simulation to evaluate the impact and cost-effectiveness of using HCV-viremic donors for heart transplant . Methods We simulated detailed histories from time of listing until death for the real-world cohort of all adults listed for heart transplant in the United States from July 2014 to June 2019 (n = 19,346). This population was imputed using historical data and captures “real-world” heterogeneity in geographic and clinical characteristics. We estimated the impact of an intervention in which all candidates accept HCV+ potential donors (n = 472) on transplant volume, waitlist outcomes, and lifetime costs and quality-adjusted life years (QALYs). Results The intervention produced 232 more transplants, 132 fewer delistings due to deterioration, and 50 fewer waitlist deaths within this 5-year cohort and reduced wait times by 3% to 11% (varying by priority status). The intervention was cost-effective, adding an average of 0.08 QALYs per patient at a cost of $124 million ($81,892 per QALY). DAA therapy and HCV care combined account for 11% this cost, with the remainder due to higher costs of transplant procedures and routine post-transplant care. The impact on transplant volume varied by blood type and region and was correlated with donor-to-candidate ratio (ρ = 0.71). Conclusions Transplanting HCV+ donor hearts is likely to be cost-effective and improve waitlist outcomes, particularly in regions and subgroups experiencing high donor scarcity.

We evaluated post-heart transplant (HTx) outcomes after use of higher-risk donor hearts for candidates supported with pre-HTx mechanical circulatory support (MCS).In this retrospective analysis of the national United Network for Organ Sharing registry, a total of 9,915 adult candidates on MCS underwent HTx from January 1, 2010 to March 31, 2019. Multi-organ, re-transplant, and congenital heart disease patients were excluded. Higher-risk donor organs met at least one of the following criteria: left ventricular ejection fraction50%, donor to recipient predicted heart mass ratio0.86, donor age55 years, or ischemic time4 hours. Primary outcome was 1 year post-transplant survival.Among HTx recipients, 3688 (37.2%) received higher-risk donor hearts. Candidates supported with pre-HTx extracorporeal membrane oxygenation or biventricular assist device (n = 374, 3.8%) who received higher-risk donor hearts had comparable 1 year survival (HR: 1.14, 95% CI: [0.67-1.93], p = 0.64) to recipients of standard-risk donor hearts, when adjusted for recipient age and sex. In candidates supported with intra-aortic balloon pump (n = 1391, 14.6%), transplantation of higher-risk donor hearts did not adversely affect 1 year survival (HR: 0.80, 95% CI: [0.52-1.22], p = 0.30). Patients on durable left ventricular assist devices (LVAD) who received higher-risk donor hearts had comparable 1 year survival to continued LVAD support on the waitlist, but mortality was increased compared to those who received standard-risk donor hearts (HR: 1.37, 95% CI: [1.11-1.70], p = 0.004).Patients requiring pre-HTx temporary MCS who received higher-risk donor hearts had comparable 1 year post-transplant survival to those who received standard-risk donor hearts. Stable patients on durable LVADs may benefit from waiting for standard-risk donor hearts.

Left ventricular assist devices (LVADs) have consistently and successfully improved mortality associated with end-stage heart failure. However, the definition of an "optimal" outcome post LVAD as a benchmark remains debatable. We retrospectively examined patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) between 2012 and 2016 to assess 1 year post-LVAD "optimal outcome" defined as a patient who was alive on device or transplanted, New York Heart Association functional class I/II, had no more than 2 hospitalizations at year 1, and no major adverse event. We identified the features predicting a nonoptimal outcome at 1 year. Finally, we focused on 3 years outcomes in patients implanted as destination therapy. Of the 12,566 patients in INTERMACS who received an LVAD, only 3,495 (27.8%) met our definition of optimal LVAD outcome at 1 year. These patients tended to be younger, male, and were four times more likely to be supported as bridge to transplantation. For those with optimal outcome at year 1, their chances of long-term survival were better than those who were alive at year 1, but did not meet criteria for an optimal outcome. In the destination therapy population, only 14% of patients met the definition of an optimal outcome at 3 years. Despite significantly improved survival in patients with end-stage heart failure treated with LVAD therapy, majority patients had nonoptimal outcomes at 1 and 3 years post implant, by our definition. There is a pressing need to create a benchmark to define optimal outcomes post LVAD, both in our clinical trials and practice.

Cytomegalovirus (CMV) infection has been implicated in the pathogenesis of allograft rejection in heart transplant (HT) recipients. The effect of a CMV infection on the gene expression profiling (GEP, AlloMap) scores in the absence of acute rejection is not known.Data from 14,985 samples collected from 2,288 adult HT recipients enrolled in Outcomes AlloMap Registry were analyzed. Patients with known CMV serology at the time of HT who had at least 1 AlloMap score reported during follow-up were included. AlloMap scores for those patients with CMV (but no ongoing rejection) were compared with those who were never infected. An exploratory analysis on the impact of CMV on available donor-derived cell-free DNA (AlloSure) was also performed.A total of 218 patients (10%) were reported to have CMV infection after transplantation. AlloMap score in those samples with CMV infection (n = 311) had a GEP score (34; range: 29-36) significantly higher than the GEP score from samples (n = 14,674) obtained in the absence of CMV infection (30; range: 26-34; p0.0001). Both asymptomatic viremia and CMV disease demonstrated significantly higher AlloMap scores than no CMV infection samples (median scores: 33, 35, and 30, respectively; p0.0001). AlloSure levels, available for 776 samples, were not significantly different (median: 0.23% in 18 samples with CMV infection vs 0.15% in 776 samples without CMV infection; p = 0.66).CMV infection in HT recipients is associated with an increase in AlloMap score, whereas AlloSure results do not appear to be impacted. This information should be considered when clinically interpreting abnormal/high AlloMap scores in HT recipients.

BACKGROUND Currently, there are no simple tools to evaluate the acute heart failure (HF) symptom severity in children hospitalized with acute decompensated HF (ADHF). We sought to develop an inpatient HF score (HFS) that could be used as a clinical tool and for clinical trials. METHODS Pediatric HF clinicians at Stanford reviewed the limitations of existing HFSs, which include lack of calibration to the inpatient setting, omission of gastrointestinal symptoms, need for multiple age-based tools, and scores that prioritize treatment intensity over patient symptoms. To address these, we developed an acute HFS corresponding to the 3 cardinal symptoms of HF: difficulty with breathing, feeding, and activity. The score was iteratively improved over a 3-year pilot phase until no further changes were made. The inter-rater reliability (IRR) across a range of providers was assessed using the final version. Peak HFSs were analyzed against mortality and length of stay (LOS) for all pediatric HF discharges between July and October 2019. RESULTS The final HFS was a 4-point ordinal severity score for each of the 3 symptom domains (total score 0-12). Among clinicians who scored 12 inpatients with ADHF simultaneously, the intraclass correlation (ICC) was 0.94 (respiratory ICC = 0.89, feeding ICC = 0.85, and activity ICC = 0.80). Score trajectory reflected our clinical impression of patient response to HF therapies across a range of HF syndromes including 1- and 2-ventricle heart disease and reduced or preserved ejection fraction. Among the 28 patients hospitalized during a 3-months period (N = 28), quartiles of peak score were associated with LOS (p < 0.01) and in-hospital mortality (p < 0.01): HFS 0 to 3 (median LOS of 5 days and mortality of 0%), HFS 4 to 6 (median LOS of 18 days and mortality of 0%), HFS 5 to 9 (median LOS of 29 days and mortality of 23%), and HFS 10 to 12 (median LOS of 121 days and mortality of 50%). CONCLUSION This simple acute HFS may be a useful tool to quantify and monitor day-to-day HF symptoms in children hospitalized with ADHF regardless of etiology or age group. The score has excellent IRR across provider levels and is associated with major hospital outcomes supporting its clinical validity. Validation in a multicenter cohort is warranted.

Importance The new United Network for Organ Sharing (UNOS) donor heart allocation system gives priority to patients supported with nondischargeable mechanical circulatory support (MCS) devices while awaiting heart transplant. Whether there has been a change in temporary MCS use in cardiac intensive care units (CICUs) since the implementation of this policy is unknown. Objectives To examine whether the UNOS donor heart allocation system revision in October 2018 was associated with changes in temporary MCS use in CICUs and whether temporary MCS use differed between US transplant centers and US nontransplant centers and Canadian centers. Design, Setting, and Participants In this cohort study, 14 centers from the Critical Care Cardiology Trials Network (CCCTN), a multicenter network of tertiary CICUs in North America, contributed 2-month snapshots of consecutive medical CICU admissions between September 1, 2017, and September 1, 2018 (prerevision period), and October 1, 2018, and September 1, 2019 (postrevision period). CICUs were classified as US transplant centers (n = 7) or other CICUs (US nontransplant centers or Canadian centers; n = 7). Exposure Revision to the UNOS donor heart allocation system. Main Outcomes and Measures Treatment with temporary MCS (intra-aortic balloon pump, microaxial intracardiac ventricular assist device, percutaneous centrifugal ventricular assist device, venoarterial extracorporeal membrane oxygenation, or surgically implanted, nondischargeable MCS device) during hospital admission. Results A total of 384 admissions for acute, decompensated, heart failure–related cardiogenic shock (ADHF-CS) were included, among which 248 (64.6%) were to US transplant centers; 126 admissions (51%) were in the prerevision period and 122 (49%) were in the postrevision period. The mean (SD) patient age was 61.2 (14.6) years; 246 patients (64.1%) were male. The proportion of admissions with ADHF-CS managed with temporary MCS at US transplant centers significantly increased from 25.4% (32 of 126 admissions) before to 42.6% (52 of 122 admissions) after the UNOS allocation system changes (P = .004). In other CICUs, the proportion did not significantly change (24.5% [13 of 53 admissions] to 24.1% [20 of 83 admissions];P = .95). After multivariable adjustment, patients admitted to US transplant centers in the postrevision period were more likely to receive temporary MCS compared with those admitted in the prerevision period (adjusted odds ratio, 2.19; 95% CI, 1.13-4.24;P = .02). Conclusions and Relevance In the year after implementation of the new UNOS donor heart allocation system, temporary MCS use in patients admitted with ADHF-CS increased in US transplant centers but not in other CICUs. Whether this shift in practice will affect outcomes of patients with ADHF-CS or organ distribution should be evaluated.

Driveline infection (DLI) is a cause of morbidity and mortality in patients with continuous-flow left ventricular assist devices (CF-LVADs). We hypothesized that an alternate dressing protocol would decrease the rate of DLIs.A retrospective review of CF-LVAD implants at a single institution from January 2010 to October 2015 was conducted. Patients were divided into implants before (group 1) and after (group 2) the introduction of the new protocol on September 1, 2012. Patients were followed until death, transplantation, change in dressing type, or 2 years. 153 patients were included: 61 in group 1 and 92 in group 2. Group 1 had fewer HVADs than group 2 (27.9% vs 71.7%; P.001) and more destination therapy, although the latter was not statistically significant (50.8% vs 34.8%; P = .118). At 24 months, the freedom from DLI was 53% in group 1 and 89% in group 2 (P = .01). Group 1 had a significantly greater risk of DLI than group 2 (incident rate ratio 3.18, 95% confidence interval 1.23-8.18; P = .016).Dramatic improvement in freedom from DLI at 2 years was achieved with a new driveline dressing protocol. This demonstrates that DLI rates can be improved with alternate percutaneous site care techniques in CF-LVAD patients.

Objectives This study sought to determine if indication for support affects the outcomes after temporary right ventricular mechanical circulatory support after postcardiotomy cardiogenic shock, cardiac transplant, or left ventricular assist device placement. Methods A retrospective review was performed on 80 patients receiving a right ventricular assist device. Data were collected from a prospectively maintained database. Kaplan–Meier survival analysis was performed to compare survival between groups. Multivariate regression analysis was performed to identify risk factors for failure to wean from support. Results The indication for support was postcardiotomy cardiogenic shock in 13 patients (16%), cardiac transplant in 25 patients (31%), and left ventricular assist device in 42 patients (53%). Median support time was 6 days. Device was successfully weaned in 6 postcardiotomy cardiogenic shock cases (46%), 21 cardiac transplant cases (84%), and 35 left ventricular assist device cases (83%). Survival was worse for patients with postcardiotomy cardiogenic shock compared with patients with a left ventricular assist device. Survival up to 3 months was better for patients who received immediate (n = 43) versus delayed (n = 37) support (79% vs 46%, P = .003). Weaning and survival remained static across implant era. Risk factor analysis identified postcardiotomy cardiogenic shock indication (odds ratio, 0.161; P = .007; confidence interval, 0.043-0.600) as an independent negative predictor of weaning from mechanical support. Conclusions Temporary right ventricular mechanical support remains an effective treatment strategy after left ventricular assist device placement with immediate support resulting in superior short-term survival. Caution should be applied in postcardiotomy cardiogenic shock when weaning and survival are poor. Overall survival outcomes have remained relatively static over time.

Objectives This study investigates the use of a Bayesian statistical models to predict survival at various time points in patients undergoing left ventricular assist device (LVAD) implantation. Background LVADs are being increasingly used in patients with end-stage heart failure. Appropriate patient selection continues to be key in optimizing post-LVAD outcomes. Methods Data used for this study were derived from 10,277 adult patients from the INTERMACS (Inter-Agency Registry for Mechanically Assisted Circulatory Support) who had a primary LVAD implanted between January 2012 and December 2015. Risk for mortality was calculated retrospectively for various time points (1, 3, and 12 months) after LVAD implantation, using multiple pre-implantation variables. For each of these endpoints, a separate tree-augmented naive Bayes model was constructed using the most predictive variables. Results A set of 29, 26, and 31 pre-LVAD variables were found to be predictive at 1, 3, and 12 months, respectively. Predictors of 1-month mortality included low Inter-Agency Registry for Mechanically Assisted Circulatory Support profile, number of acute events in the 48 h before surgery, temporary mechanical circulatory support, and renal and hepatic dysfunction. Variables predicting 12-month mortality included advanced age, frailty, device strategy, and chronic renal disease. The accuracy of all Bayesian models was between 76% and 87%, with an area under the receiver operative characteristics curve of between 0.70 and 0.71. Conclusions A Bayesian prognostic model for predicting survival based on the comprehensive INTERMACS registry provided highly accurate predictions of mortality based on pre-operative variables. These models may facilitate clinical decision-making while screening candidates for LVAD therapy.

The field of mechanical circulatory support has been impacted by the approval of new continuous-flow left ventricular assist devices (LVADs) and changes to the United States heart allocation system.Primary isolated continuous-flow LVAD implants in The Society of Thoracic Surgeons Intermacs registry from January 2014 through September 2019 were evaluated. Survival and freedom from major adverse events were compared between axial-flow, centrifugal-flow with hybrid levitation (CF-HL), and centrifugal-flow with full magnetic levitation (CF-FML) devices.Of 2603 devices implanted in 2014, 1824 (70.1%) were axial flow and 1213 (46.6%) were destination therapy (DT); through September 2019, 1752 devices were implanted, but only 37 (2.1%) were axial flow and 1230 (70.2%) were DT. Implants were performed in 13,016 patients between 2014 and 2018. Patients receiving implants in 2017-2018 compared with 2014-2016 were more likely to be at Intermacs profile 1 (17.1% vs 14.3%, P.001) and to have preimplant temporary mechanical circulatory support (34.8% vs 29.3%, P.001). Overall survival and freedom from major adverse events were higher with CF-FML devices. In multivariable analysis of survival between CF-HL and CF-FML, device type was not a significant early hazard, but the use of CF-HL devices had a late hazard ratio for death of 3.01 (P .001).Over the past 5 years, centrifugal-flow LVADs have become the dominant technology and DT the most common implant strategy. While outcomes with CF-FML devices are promising, comparisons with other devices from nonrandomized registry studies should be made with caution.

Background: Reports of left ventricular assist device (LVAD) malfunction have focused on pump thrombosis. However, the device consists of the pump, driveline, and peripherals, all of which are potentially subject to failure. Methods: Prospectively collected data were reviewed for all LVAD device malfunctions (DMs) occurring in rotary LVADs implanted at a single center between April 2004 and May 2016. Durable LVADs included 108 Heartmate II (HM II) and 105 HeartWare VAD (HVAD). DM data were categorized according to device type and into categories related to the component that failed: (1) controller, (2) peripheral components, and (3) implantable blood pump or its integral electric driveline. Pump-related events were analyzed as pump-specific (suspected or confirmed thrombosis) or nonpump-specific (driveline failure). DM rates were reported as events per 1000 patient-days, and Cox proportional hazard models were used for time-to-event analyses. Cumulative rates of malfunction were examined for the main components of each type of LVAD. Results: Types of DM included controller failure (30%), battery failure (19%), or patient cable failure (14%), whereas only 13% were because of pump failure. DMs were more common in the HM II device (3.73 per 1000 patient-days versus 3.06 per 1000 patient-days for the HVAD, P P P P P Conclusions: Device malfunction is much broader than pump failure alone and occurs for different components at different rates based on the type of LVAD.

Background Right ventricular failure (RVF) complicates 9% to 44% of left ventricular assist device (LVAD) implants post-operatively. Current prediction scores perform only modestly in validation studies, and do not include immune markers. Chemokines are inflammatory signaling molecules with a fundamental role in cardiac physiology and stress adaptation. In this study we investigated chemokine receptor regulation in LVAD recipients who develop RVF. Methods Expression of chemokine receptor (CCR) genes 3 to 8 were examined in the peripheral blood of 111 LVAD patients, collected 24 hours before implant. RNA was isolated using a PAXgene protocol. Gene expression was assessed using a targeted microarray (RT2 Profiler PCR Array; Qiagen). Results were expressed as polymerase chain reaction (PCR) cycles to threshold and normalized to the average of 3 control genes, glyceraldehyde phosphate dehydrogenase (GAPDH), hypoxanthine phosphoribosyltransferase 1 (HPRT1) and β 2 -microglobulin (B2M). Secondary outcomes studied were 1-year mortality and long-term RV failure (RVF-LT). Results CCR3, CCR4, CCR6, CCR7 and CCR8 were downregulated in LVAD recipients with RVF. Within this cohort of patients, CCR4, CCR7 and CCR8 were further downregulated in those who required RV mechanical support. In addition, under-expression of CCR3 to CCR8 was independently associated with an increased risk of mortality at 1 year, even after adjusting for RVF. CCR expression did not predict RVF-LT in our patient cohort. Conclusions Pre-LVAD CCR downregulation is associated with RVF and increased mortality after implant. Inflammatory signatures may play a major role in prognostication in this patient population.

Introduction: The planned use of a temporary right ventricular assist device (RVAD) at the time of left ventricular assist device (LVAD) implantation may prevent the need for a permanent biventricular assist device (BiVAD). Herein we describe our RVAD weaning protocol that was effectively employed in 4 patients to prevent the need for permanent BiVAD. Methods: Four patients in refractory cardiogenic shock underwent planned RVAD insertion during LVAD implantation due to severely depressed right ventricular function with dilation preoperatively. A standardized RVAD weaning protocol was employed in these 4 patients in preparation for decannulation. Results: Temporary RVADs were successfully placed in all 4 patients at the time of LVAD implantation. All patients survived to RVAD decannulation and discharge and were alive at the time of most recent follow-up (range, 528-742 days post–RVAD decannulation). Conclusion: Planned implantation of a temporary RVAD in high risk patients may avoid the need for biventricular mechanical support in the future.

BACKGROUND Cardiac allograft vasculopathy (CAV) is the leading cause of late graft loss. While there are numerous post-transplant factors which may increase the risk of the development of CAV, there is a paucity of data on the impact of donor-derived atherosclerosis (DA), early discontinuation of prednisone, and early initiation of proliferation signal inhibitors (PSI) as assessed by intravascular ultrasound (IVUS). METHODS Retrospective single-center study of all adult transplant patients (2008-2017) with serial IVUS at baseline and annually for 5 years. DA was defined as a baseline maximal intimal thickness (MIT) ≥0.5 mm, and CAV development was defined as MIT ≥1 mm or an increase in MIT ≥0.5 mm at year 1 compared with baseline or an increase in 0.3 mm annually thereafter. Clinical risk factors for CAV were identified using multivariable hazard regression. Separate multistate models were applied to assess the association of prednisone discontinuation and PSI initiation and CAV. RESULTS Of 282 patients screened, 186 patients had a 1-year angiogram. The mean age of those included in the cohort was 51 ± 11 years, 70% were male, 58% were Caucasian, and 27% were supported by a left ventricular assist device. Donor atherosclerosis was present in 40%. The cumulative incidence of CAV at 5 years is 41% in DA- vs. 59% in DA + (p = .012). Donor age was a strong predictor of DA (p = .016). Significant risk factors for CAV included male sex (HR = 4.141, p = .001), non-Caucasian race (HR = 1.98, p = .011), BMI

Background: Temporary mechanical circulatory support (MCS) devices provide hemodynamic assistance for shock refractory to pharmacological treatment. Most registries have focused on single devices or specific etiologies of shock, limiting data regarding overall practice patterns with temporary MCS in cardiac intensive care units. Methods: The CCCTN (Critical Care Cardiology Trials Network) is a multicenter network of tertiary CICUs in North America. Between September 2017 and September 2018, each center (n=16) contributed a 2-month snapshot of consecutive medical CICU admissions. Results: Of the 270 admissions using temporary MCS, 33% had acute myocardial infarction-related cardiogenic shock (CS), 31% had CS not related to acute myocardial infarction, 11% had mixed shock, and 22% had an indication other than shock. Among all 585 admissions with CS or mixed shock, 34% used temporary MCS during the CICU stay with substantial variation between centers (range: 17%–50%). The most common temporary MCS devices were intraaortic balloon pumps (72%), Impella (17%), and veno-arterial extracorporeal membrane oxygenation (11%), although intraaortic balloon pump use also varied between centers (range: 40%–100%). Patients managed with intraaortic balloon pump versus other forms of MCS (advanced MCS) had lower Sequential Organ Failure Assessment scores and less severe metabolic derangements. Illness severity was similar at high- versus low-MCS utilizing centers and at centers with more advanced MCS use. Conclusions: There is wide variation in the use of temporary MCS among patients with shock in tertiary CICUs. While hospital-level variation in temporary MCS device selection is not explained by differences in illness severity, patient-level variation appears to be related, at least in part, to illness severity.

Background: Currently, women represent Methods and Results: Using the International Society for Heart and Lung Transplantation Registry, we performed descriptive analyses and estimated overall freedom from posttransplant death stratified by sex using Kaplan-Meier survival methods. Male and female recipients were matched according to the Index for Mortality Prediction After Cardiac Transplantation and Donor Risk Index score using 1:1 propensity score matching. The study cohort comprised 34 198 heart transplant recipients (76.3% men, 23.7% women) between 2004 and 2014. Compared with men, women were more likely younger (51 [39–59] versus 55 [46–61] years; P P P P P =0.002), tobacco use (36.5% versus 52.3%; P P P P P =0.03) or durable ventricular assist device (22% versus 31.5%; P P P =0.57). Conclusions: Overall survival does not differ between men and women after cardiac transplantation. Women who survive to heart transplantation appear to have lower risk features than male recipients but receive hearts from higher risk donors.

Background Despite significant advances in durable mechanical support survival, infectious complications remain the most common adverse event after ventricular assist device (VAD) implantation and the leading cause of early death after transplantation. In this study, we aim to describe our local infectious epidemiology and review short-term survival and infectious incidence rates in the post-transplantation period and assess risk factors for infectious episodes after transplantation. Methods Retrospective single-center study of all consecutive adult heart transplant patients from 2008 to 2017. Survival data were estimated and summarized using the Kaplan-Meier method. We quantified and evaluated the difference in the incidence rate between patients with and without infection using a Fine-Gray model. The outcome of interest is the time to first infection diagnosis with post-transplant death as the competing event. Results Among 278 heart transplant patients, 74 (26.5%) underwent LVAD implantation. Twenty-one patients (28.3%) developed an infection while supported by an LVAD. When compared to patients supported by an LVAD without a preceding infection, BMI was significantly greater (31.2 vs 27.8 kg/m2 , P = .03). Median follow-up post-transplantation was 3.01 years. Significant risk factors for the competing risk regression for infection after heart transplantation include LVAD infection (HR 1.94, [95% CI] 1.11-3.39, P = .020) and recipient COPD (HR 2.14, [95% CI] 1.39-3.32, P = .001) when adjusted for recipient age, gender, hypertension, diabetes mellitus, and body mass index. Conclusions Patients with LVAD-related infection had a significantly increased risk of infectious complications after heart transplantation. Further research on the avoidance of induction agents and reduced maintenance immunosuppression in this patient population is warranted.

Heart transplant (HTx) recipients are at increased risk of pericardial disease. Idiopathic recurrent pericarditis has not been previously described following HTx. We describe a 35-year-old male who was admitted with pericarditis and moderate pericardial effusion 10 months after HTx. Two weeks before his admission, his prednisone had been tapered off. A thorough infectious workup and endomyocardial biopsy was unrevealing. He was started on colchicine with the addition of tapering prednisone regimen of 40 mg daily due to unresolved pain. Over the next several years, he had three recurrent episodes of pericarditis requiring re-initiation of prednisone with extensive investigations negative for rejection, autoimmune, and infectious causes. Cardiac MRI confirmed pericardial inflammation. Due to his recurrent course and inability to wean off prednisone, anakinra, an IL-1 receptor antagonist, was started at 100 mg sc daily. This allowed successful discontinuation of prednisone. He is now 34 months post-transplant without recurrence on anakinra and colchicine maintenance. Due to the overlap between idiopathic recurrent pericarditis and auto-inflammatory diseases, there is growing evidence for utilizing IL-1 receptor antagonists in this condition. While pericarditis is common in the HTx population, this is the first report of successful use of an IL-1 receptor blocker for pericarditis in this population.

Hemodynamic ramp (HR) tests can guide the optimization of left ventricular assist device (LVAD) speed and direct medical therapy. We investigated the effects of HR-guided LVAD management.This prospective, multicenter, randomized, pilot study compared outcomes in LVAD patients using an HR-guided (HR group) versus a standard transthoracic echocardiography-guided (control group) management strategy. Patients were enrolled and randomized 1 to 3 months post-HVAD implantation and followed for 6 months. Twenty-two patients (57±10 years, 73% male) were randomized to the HR group and 19 patients (51±13 years, 63% male) to the control group. HR group patients had double the number of LVAD speed changes (1.68 versus 0.84 changes/patient, P=0.09 with an incidence rate ratio 2.0, 95% CI, 0.9-4.7) with twice the magnitude of rotations per minute changes (130 versus 60 rotations per minute/patient, P=0.004) during the study. The HR group also had 2-fold greater heart failure medication changes (4.32 versus 2.53 changes/patient, P=0.072, incidence rate ratio 1.7 with 95% CI, 0.8-3.5) predominantly because of changes in diuretic dose (40 versus 0 mg/patient, P0.001). The HR group had numerically but not statistically higher event-free survival (62% versus 46%, P=0.087; hazard ratio, 0.46 with 95% CI, 0.2-1.2), with numerically but not statistically lower events per patient-year ( P=0.084). There were no significant differences in the 6-minute walk or Kansas City Cardiomyopathy Questionnaire tests at 6 months.In this randomized pilot study of LVAD patient management we demonstrated the feasibility of standardized HR testing at multiple institutions and that a strategy guided by hemodynamics was associated with more LVAD speed and medication adjustments and a nonsignificant reduction in adverse events. A pivotal study to demonstrate the clinical benefit of HR testing is warranted.URL: https://www.clinicaltrials.gov . Unique identifier: NCT03021239.

The Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs), a joint effort among the National Heart, Lung, and Blood Institute, the Food and Drug Administration, the Centers for Medicare and Medicaid Services, and others, was established in 2005 at the University of Alabama at Birmingham. The registry examined clinical outcomes and quality-of-life metrics of patients who received an Food and Drug Administration-approved durable mechanical circulatory support (MCS) device to treat advanced heart failure. On January 1, 2018, the Intermacs Database became part of The Society of Thoracic Surgeons National Database, providing additional resources for quality assessment and improvement and scientific advancement.The Intermacs Database Annual Report summarizes outcomes in patients (≥19 years of age) who underwent durable MCS implant between June 23, 2006, and December 31, 2017. Outcomes are presented for patients who underwent isolated continuous flow left ventricular assist device (CF LVAD) support, CF LVAD support with concomitant right ventricular assist device (RVAD) implant, or total artificial heart implant. Analyses of patients with CF LVADs are stratified by axial flow and centrifugal flow configurations. Because of the association of era with outcomes, the survival analyses are restricted to isolated CF LVADs implanted in the 2012 to 2016 era.There were 25,145 adult patients with MCS reported to Intermacs, of whom 18,539 (74%) received CF LVADs, 667 (2.6%) had an RVAD with CF LVAD, 339 received a total artificial heart (1.3%), and 20 (0.07%) received an isolated RVAD. Of the CF LVADs, mean age was 57 ± 1 years, 26% were listed for transplantation, and 51% were in cardiogenic shock (profile 1 to 2) preoperatively. CF LVADs included 14,527 axial flow (78%) and 4,012 centrifugal flow (22%) devices. Intermacs patient phenotype has evolved over time to include more patients with profile 3 (26% in 2006 to 2011 versus 35% in 2012 to 2016) and fewer patients with profile 2 (40% versus 35%), patients with better markers of preoperative renal and hepatic function, and more patients who received implants for destination therapy (29% versus 48%) indication. In 2017, centrifugal flow implants (51%) approximated that of axial flow devices (49%). Mean CF LVAD support duration was 20 months (31,563 patient-years). One-year survival for isolated CF LVADs was 83% and 5-year survival was 46%. One-year survivals for centrifugal versus axial flow devices were 85% and 84%, respectively. Patients who required concomitant RVAD support had 1- and 5-year survivals of 58% and 28%, respectively. Freedom from all-cause readmission was 70% at 1 month and 20% at 1 year. At 1 year, stroke occurred in 20% of patients on centrifugal flow and 13% of patients on axial flow support (p0.001), gastrointestinal bleeding affected 20% of patients with centrifugal flow devices and 25% of patients with axial flow devices (p0.001), and pump-related infection occurred in 28% of patients with centrifugal flow devices versus 25% of patients with axial flow devices (p = 0.01). Neurologic dysfunction (19% of deaths) and multisystem organ dysfunction (15%) were the most common causes of death.With the evolution of MCS, patient phenotype and outcomes are also changing over time. CF LVAD support is increasingly being used in the less ill patient phenotype and more patients are supported for destination therapy. Mean survival is now approaching 5 years, but adverse events, especially neurologic events, continue to have a detrimental impact on the success of CF LVAD support.

Strategies to improve donor heart utilization are required in the setting of limited donor availability. One innovative strategy is to consider the use of hepatitis C viremic (HCV) nucleic acid amplification test positive donors in hepatitis C-negative recipients, given the availability of highly effective direct acting antiviral agents. We utilized United Network for Organ Sharing data to evaluate the geographic distribution, clinical characteristics, and post-transplant outcomes of HCV+ donor hearts.The United Network for Organ Sharing registry was queried for all HCV+ recovered donors and those considered for heart donation classified by sex, age group, United Network for Organ Sharing region, and cause of death from January 1, 2014, to December 31, 2017. Propensity score matching (3:1) was applied to the recipients based on the index for mortality prediction after cardiac transplantation score and donor risk index. A total of 1306 HCV+ donors were recovered from 2014 to 2017 of whom 1078 (82.5%) were 18 to 49 and predominantly from the Appalachia region (United Network for Organ Sharing regions 2, 3, and 11). A total of 64 (5%) HCV+ donor hearts were transplanted in this interval. The match-adjusted risk difference in survival was estimated to be 0.87% ( P=0.83) at 12 months.To meet the demands of heart transplantation, we must consider additional strategies to expand the donor pool. From 2014 to 2017, despite availability of highly effective direct acting antiviral therapy, only 5% of HCV+ donor hearts were accepted for transplantation. National efforts may be required to capitalize on this resource while we continue to carefully monitor the safety of this novel approach.

Who wants a left ventricular assist device for ambulatory heart failure? Early insights from the MEDAMACS screening pilot Garrick C. Stewart, MD, MPH, Michelle M. Kittleson, MD, PhD, Jennifer A. Cowger, MD, Frances L. Johnson, MD, Chetan B. Patel, MD, Maria M. Mountis, DO, Parag C. Patel, MD, J. Eduardo Rame, MD, Jeffrey Testani, MD, Maya E. Guglin, MD, Jeffrey J. Teuteberg, MD, and Lynne W. Stevenson, MD From the Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, Massachusetts; Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California; Cardiovascular Center, University of Michigan, Ann Arbor, Michigan; Division of Cardiology, University of Iowa, Iowa City, Iowa; Division of Cardiology, Duke University, Durham, North Carolina; Division of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio; Division of Cardiology, University of Texas Southwestern, Dallas, Texas; Heart and Vascular Center, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Cardiology, University of South Florida, Tampa, Florida; and the Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania

Patients with failing Fontan physiology and liver cirrhosis are being considered for combined heart and liver transplantation. We performed a retrospective review of our experience with en bloc combined heart and liver transplantation in Fontan patients > 10 years old from 2006 to 18 per Institutional Review Board approval. Six females and 3 males (median age 20.7, range 14.2-41.3 years) underwent en bloc combined heart and liver transplantation. Indications for heart transplant included ventricular dysfunction, atrioventricular valve regurgitation, arrhythmia, and/or lymphatic abnormalities. Indication for liver transplant included portal hypertension and cirrhosis. Median Fontan/single ventricular end-diastolic pressure was 18/12 mm Hg, respectively. Median Model for End-Stage Liver Disease excluding International Normalized Ratio score was 10 (7-26), eight patients had a varices, ascites, splenomegaly, thrombocytopenia score of ≥ 2, and all patients had cirrhosis. Median cardiopulmonary bypass and donor ischemic times were 262 (178-307) and 287 (227-396) minutes, respectively. Median intensive care and hospital stay were 19 (5-96) and 29 (13-197) days, respectively. Survival was 100%, and rejection was 0% at 30 days and 1 year post-transplant. En bloc combined heart and liver transplantation is an acceptable treatment in the failing Fontan patient with liver cirrhosis.

Dyslipidemia is common in patients undergoing heart transplantation and is associated with the progression of cardiac allograft vasculopathy. Two monoclonal antibodies directed against PCSK9i-evolocumab and alirocumab-are currently available. However, their use, safety and efficacy in the post-transplant setting have not been studied. We present our experience with 6 heart transplant recipients treated with a PCSK9i. A > 70% reduction in LDL-cholesterol was observed after evolocumab therapy. PCSK9 inhibitors are a potentially lipid-lowering therapeutic option for heart transplant patients with suboptimal LDL despite maximal tolerated statin doses.

The number of patients with end-stage heart failure (HF) continues to increase over time, but there has been little change in the availability of organs for cardiac transplantation, intensifying the demand for left ventricular assist devices (LVADs) as a bridge to transplantation. There is also a growing number of patients with end-stage HF who are not transplant candidates but may be eligible for long-term support with an LVAD, known as destination therapy. Due to this increasing demand, LVAD technology has evolved, resulting in transformative improvements in outcomes. Additionally, with growing clinical experience patient management continues to be refined, leading to iterative improvements in outcomes. With outcomes continuing to improve, the potential benefit from LVAD therapy is being considered for patients earlier in their course of advanced HF. We review recent changes in technology, patient management, and implant decision making in LVAD therapy.

BACKGROUND Gene expression profiling (GEP) was developed for non-invasive surveillance of acute cellular rejection . Despite its widespread use, there has been a paucity in outcome data for patients managed with GEP outside of clinical trials. METHODS The Outcomes AlloMap Registry (OAR) is an observational, prospective, multicenter study including patients aged ≥ 15 years and ≥ 55 days post-cardiac transplant. Primary outcome was death and a composite outcome of hemodynamically significant rejection, graft dysfunction , retransplantation , or death. Secondary outcomes included readmission rates and development of coronary allograft vasculopathy and malignancies. RESULTS The study included 1,504 patients, who were predominantly Caucasian (69%), male (74%), and aged 54.1 ± 12.9 years. The prevalence of moderate to severe acute cellular rejection (≥2R) was 2.0% from 2 to 6 months and 2.2% after 6 months. In the OAR there was no association between higher GEP scores and coronary allograft vasculopathy (p = 0.25), cancer (p = 0.16), or non-cytomegalovirus infection (p = 0.10). Survival at 1, 2, and 5 years post-transplant was 99%, 98%, and 94%, respectively. The composite outcome occurred in 103 patients during the follow-up period. GEP scores in dual-organ recipients (heart-kidney and heart-liver) were comparable to heart-alone recipients. CONCLUSIONS This registry comprises the largest contemporary cohort of patients undergoing GEP for surveillance. Among patients selected for GEP surveillance, survival is excellent, and rates of acute rejection, graft dysfunction, readmission, and death are low.

Background Patients with heart failure (HF) are admitted either under observation (OBS) or inpatient stays; however, there is little data on whether this designation reflects the clinical status of a patient, with significant logistical and financial implications. We sought to compare the outcomes of patients with HF admitted OBS versus inpatient stay (≤2 days; INPT). Methods and Results From January 1, 2008 to September 30, 2015, our multisite health system saw 21 339 unique patients totaling 52 493 hospital admissions with a primary diagnosis of HF . Patients were excluded if they underwent cardiac surgery (n=611), heart transplantation (n=187), or left ventricular assist device insertion (n=198), or if they died during hospitalization (n=1839). Of the remaining 50 654 discharges, 2 groups were identified: INPT group and OBS group. Outcomes were HF readmission, all‐cause readmission, and all‐cause mortality within 1 year of discharge. Hazard ratios were computed using the Andersen‐Gill method in the Cox proportional‐hazards model. A total of 8709 admissions (17%) occurred in the INPT group and 2648 admissions (5%) occurred in the OBS group. HF readmission rate at 1 year was 55.3% in INPT versus 66.5% in OBS (hazard ratio, 0.75; 95% confidence interval, 0.71–0.80; P INPT versus 82.5% in OBS (hazard ratio, 0.74; 95% confidence interval, 0.70–0.78; P INPT versus 24.2% of OBS (hazard ratio, 1.03; 95% confidence interval, 0.95–1.12; P =0.46). Conclusions HF admissions designated INPTs were associated with lower readmission rates and equivalent mortality to those designated OBS.

Background Right ventricular (RV) failure is a significant complication after implantation of a left ventricular assist device (LVAD). It is therefore important to identify patients at risk a priori. However, prognostic models derived from multivariate analyses have had limited predictive power. Methods This study retrospectively analyzed the records of 183 LVAD recipients between May 1996 and October 2009; of these, 27 later required a RVAD (RVAD + ) and 156 remained on LVAD only (RVAD − ) until transplant or death. A decision tree model was constructed to represent combinatorial non-linear relationships of the pre-operative data that are predictive of the need for RVAD support. Results An optimal set of 8 pre-operative variables were identified: transpulmonary gradient, age, right atrial pressure, international normalized ratio, heart rate, white blood cell count, alanine aminotransferase, and the number of inotropic agents. The resultant decision tree, which consisted of 28 branches and 15 leaves, identified RVAD + patients with 85% sensitivity, RVAD − patients with 83% specificity, and exhibited an area under the receiver operating characteristic curve of 0.87. Conclusions The decision tree model developed in this study exhibited several advantages compared with existing risk scores. Quantitatively, it provided improved prognosis of RV support by encoding the non-linear, synergic interactions among pre-operative variables. Because of its intuitive structure, it more closely mimics clinical reasoning and therefore can be more readily interpreted. Further development with additional multicenter, longitudinal data may provide a valuable prognostic tool for triage of LVAD therapy and, potentially, improve outcomes.

The basis for increased mortality after heart transplantation in African Americans and other non-Caucasian racial groups is poorly defined. We hypothesized that increased risk of adverse events is driven by biologic factors. To test this hypothesis in the Invasive Monitoring Attenuation through Gene Expression (IMAGE) study, we determined whether the event rate of the primary outcome of acute rejection, graft dysfunction, death, or retransplantation varied by race as a function of calcineurin inhibitor (CNI) levels and gene expression profile (GEP) scores.We determined the event rate of the primary outcome, comparing racial groups, stratified by time after transplant. Logistic regression was used to compute the relative risk across racial groups, and linear modeling was used to measure the dependence of CNI levels and GEP score on race.In 580 patients monitored for a median of 19 months, the incidence of the primary end point was 18.3% in African Americans, 22.2% in other non-Caucasians, and 8.5% in Caucasians (p0.001). There were small but significant correlations of race and tacrolimus trough levels to the GEP score. Tacrolimus levels were similar among the races. Of patients receiving tacrolimus, other non-Caucasians had higher GEP scores than the other racial groups. African American recipients demonstrated a unique decrease in expression of the FLT3 gene in response to higher tacrolimus levels.African Americans and other non-Caucasian heart transplant recipients were 2.5-times to 3-times more likely than Caucasians to experience outcome events in the Invasive Monitoring Attenuation through Gene Expression study. The increased risk of adverse outcomes may be partly due to the biology of the alloimmune response, which is less effectively inhibited at similar tacrolimus levels in minority racial groups.

Recent Organ Procurement and Transplantation Network bylaw revisions mandate that US transplant programs have an "approved pediatric component" in order to perform heart transplantation (HT) in patients18 years old. The impact of this change on adolescents, a group known to be at high risk for graft loss and nonadherence, is unknown. We studied all US primary pediatric (age18 years) HT from 2000 to 2015 to compare graft survival between centers organized mainly for adult versus pediatric care. Centers were designated as pediatric- or adult-specialty care according to the ratio of pediatric:adult HT performed and minimum age of HT (pediatric-specialty defined as ratio0.7; adult-specialty ratio0.05 and minimum age8 years). In propensity score-matched cohorts, we observed no difference in graft loss by center type (median survival: adult 12.4 years vs pediatric 9.2 years, P = .174). Compared to the matched pediatric cohort, adult-specialty center recipients lived closer to their transplant center (31 vs 45 miles, P = .012), and trended toward fewer out-of-state transplants (15 vs 25%, P = .082). Our data suggest that select adolescents can achieve similar midterm graft survival at centers organized primarily for adult HT care. Regardless of post-HT setting, the development of care models that demonstrably improve adherence may be of greatest benefit to improving survival of this high-risk population.

Background: To investigate preimplant risk factors associated with early right ventricular assist device (RVAD) use in patients undergoing continuous-flow left ventricular assist device (LVAD) surgery. Methods and Results: Patients in the Interagency Registry for Mechanically Assisted Circulatory Support who underwent primary continuous-flow–LVAD surgery were examined for concurrent or subsequent RVAD implantation within 14 days of LVAD. Risk factors for RVAD implantation and the combined end point of RVAD or death within 14 days of LVAD were assessed with stepwise logistic regression. We compared survival between patients with and without RVAD using Kaplan–Meier method and Cox proportional hazards modeling. Of 9976 patients undergoing continuous-flow–LVAD implantation, 386 patients (3.9%) required an RVAD within 14 days of LVAD surgery. Preimplant characteristics associated with RVAD use included interagency registry for mechanically assisted circulatory support patient profiles 1 and 2, the need for preoperative extracorporeal membrane oxygenation or renal replacement therapy, severe preimplant tricuspid regurgitation, history of cardiac surgery, and concomitant procedures other than tricuspid valve repair at the time of LVAD. Hemodynamic determinants included elevated right atrial pressure, reduced pulmonary artery pulse pressure, and reduced stroke volume. The final model demonstrated good performance for both RVAD implant (area under the curve, 0.78) and the combined end point of RVAD or death within 14 days (area under the curve, 0.73). Compared with patients receiving an isolated LVAD, patients requiring RVAD had decreased 1- and 6-month survival: 78.1% versus 95.8% and 63.6% versus 87.9%, respectively ( P Conclusions: The need for RVAD implantation after LVAD is associated with indices of global illness severity, markers of end-organ dysfunction, and profiles of hemodynamic instability.

Objectives This study assessed patient and physician perceptions of heart failure (HF) disease severity and treatment options. Background The prognosis for ambulatory patients with advanced HF on medical therapy is uncertain, yet has important implications for decision making regarding transplantation and left ventricular assist device (LVAD) placement. Methods Ambulatory patients with advanced HF (New York Heart Association functional class III to IV, Interagency Registry for Mechanically Assisted Circulatory Support profiles 4 to 7) on optimized medical therapy were enrolled across 11 centers. At baseline, treating cardiologists rated patients for perceived risk for transplant, LVAD, or death in the upcoming year. Patients were also surveyed about their own perceptions of life expectancy and willingness to undergo various interventions. Results At enrollment, physicians regarded 111 of 161 patients (69%) of the total cohort to be at high risk for transplant, LVAD, or death, whereas only 23 patients (14%) felt they were at high risk. After a mean follow-up of 13 months, 61 patients (38%) experienced an endpoint of 33 deaths (21%), 13 transplants (8%), and 15 LVAD implants (9%). There was poor discrimination between risk prediction among both patients and physicians. Among physician-identified high-risk patients, 77% described willingness to consider LVAD, but 63% indicated that they would decline 1 or more other simpler forms of life-sustaining therapy such as ventilation, dialysis, or a feeding tube. Conclusions Among patients with advanced HF, physicians identified most to be at high risk for transplantation, LVAD, or death, whereas few patients recognized themselves to be at high risk. Patients expressed inconsistent attitudes toward lifesaving treatments, possibly indicating poor understanding of these therapies. Educational interventions regarding disease severity and treatment options should be introduced prior to the need for advanced therapies such as intravenous inotropic therapy, transplantation, or LVAD.

Cardiologists need to decide which treatments are appropriate for seriously ill patients and whether they align with patient goals. Reconciling medical options with patients' wishes requires skilled communication. Although there is evidence that communication is teachable, few cardiologists receive formal training.To demonstrate that providing communication skills training to cardiologists is feasible and improves their perceived preparedness (PP) for leading difficult conversations.CardioTalk is a workshop to improve communication through short didactic sessions followed by interactions with standardized patients. Competencies include giving bad news, defining goals of care, responding to emotion, supporting religious beliefs, and withdrawing therapies. Settings/Subjects: First year cardiology fellows, heart failure fellows, and cardiac intensive care unit attendings.Surveys evaluated the curriculum's efficacy and learners' PP before and after the workshop.Eight cardiology attendings and 20 cardiology fellows participated. Eighty-nine percent reported having any prior education in communication. Fellows reported more prior education than attendings (100% vs. 62.5%, p = 0.017). Level of PP improved in all competencies for all learners. Ninety-six percent of respondents would recommend the training to peers. All attendings felt that it should be required for cardiologists in the cardiac intensive care unit and reported improved preparedness to teach communication to learners.All learners improved in levels of PP in communication competencies. CardioTalk is the first described training program that prepares cardiologists for the challenges they face when having conversations with seriously ill patients.

Background The left atrium (LA) in the transplanted heart (TH) is a surgically created chamber from variable portions of donor and recipient LA. The American Society of Echocardiography (ASE) recommends measuring LA size in native hearts using biplane LA volume index (LAVI) as a more accurate measurement than LA anterior-posterior diameter (LA-APD). We hypothesized that LA-APD underestimates LA size when compared with LAVI in the TH. Methods Patients with a TH from 1/05 to 1/10 who had a transthoracic echocardiogram within 24 months of transplant were studied. Patients were excluded if they had an ejection fraction mild aortic or mitral regurgitation, or poor image quality. Echocardiograms were analyzed for LA-APD and LAVI. LA size was classified as normal, mild, moderate, or severely enlarged based on age and sex specific cutoffs per the ASE. Results Of 297 patients evaluated, 160 met inclusion criteria. Mean age was 57 ± 13 years and 79% were males. Mean LA-APD and LAVI were 4.3 ± 0.6 cm and 36 ± 14 mL/m2, respectively. LAVI correlated with LA-APD (r = 0.43, R2 = 0.18, P

Background Optical coherence tomography (OCT) is a novel intravascular imaging modality with excellent spatial resolution. This study explored the utility of OCT in cardiac transplantation for the detection and characterization of early changes associated with coronary allograft vasculopathy (CAV). Methods Fifteen consecutive patients, 1 to 4 years after transplant with no angiographic evidence of CAV, underwent successful OCT imaging using the Fourier-domain OCT system (C7-XR, St. Jude Medical, St. Paul, MN) in the left anterior descending artery. Analysis included measurements of the lumen, intima, and media layers, and characterization of atherosclerotic plaques. Patients were stratified by intima-to-media (I/M) ratio and classified as normal (≤1) or abnormal (>1). Results Patients were a mean of 2.8 years after transplant, 58 years old, and 92% were men. OCT imaging revealed 8 of 15 patients had intimal hyperplasia with an I/M ratio >1. Comparing those with I/M ratio of ≤1 and >1, the median (interquartile range) intimal thickness was greater (75 [70–101] vs 206 [97–269]μm, p = 0.03), whereas the media thickness was no different (72 [70–103] vs 94 [73–113]μm, p = 0.53). In addition, 7 of 15 patients had lipid-rich or calcified atherosclerotic plaques. Conclusions OCT provides high-resolution quantitative imaging of the coronary arteries and its use allows for detailed assessment of the coronary artery wall and early morphologic changes that occur after cardiac transplantation. The clinical predictive value of these OCT-derived measurements remains to be determined.

Heart transplantation in adults with congenital heart disease (CHD) has historically been associated with sub-optimal survival compared with other indications for transplantation. The purpose of this study was to evaluate survival outcomes after heart transplantation in a contemporary cohort of adults with CHD and to identify risk factors for mortality that may help guide recipient and donor selection.We performed a retrospective analysis of our adult heart transplant database, from January 2001 to February 2011, identifying 19 patients who underwent transplantation for CHD. These patients were compared with a control group of 428 patients who underwent transplantation for indications other than CHD. Kaplan-Meier survival analysis and Cox regression modeling were performed.The mean age for the CHD group was 39.4 ± 13 years vs 54.7 ± 12 years (p0.001). There was no significant difference in survival (CHD vs control) at 30 days (89% vs 92%, p = 0.5567), 1 year (84% vs 86%, p = 0.6976) or 5 years (70% vs 72%, p = 0.8478). The only significant predictor of death in the CHD group was donor organ ischemic time4 hours (HR 13.26, 95% CI 1.3 to 132.2, p = 0.028). There was no significant correlation with recipient age, history of failed Fontan surgery, pre-operative ventilator use, donor:recipient weight ratio0.8, donor:recipient CMV mismatch, model for end-stage liver disease (MELD) score or percent reactive antibody10%.In the modern era, with careful donor and recipient selection, adults with CHD have excellent early and mid-term survival after heart transplantation, rivaling that of recipients with other indications for transplantation.

A patient with a HeartMate II left ventricular assist device who had a body mass index of 52 needed gastric bypass surgery in order to qualify for a heart transplant. Unlike previous experience in which the surgery was performed at the implant hospital, the gastric bypass surgery in this case was performed at a bariatric center of excellence that was a separate facility from the implant hospital. The artificial heart program of the University of Pittsburgh Medical Center worked with the bariatric center of excellence in scheduling the gastric bypass surgery using a multidisciplinary team approach at 2 hospitals to coordinate safe, high-quality patient care in a unique situation.

Objectives This study investigates the use of a Bayesian statistical model to address the limited predictive capacity of existing risk scores derived from multivariate analyses. This is based on the hypothesis that it is necessary to consider the interrelationships and conditional probabilities among independent variables to achieve sufficient statistical accuracy. Background Right ventricular failure (RVF) continues to be a major adverse event following left ventricular assist device (LVAD) implantation. Methods Data used for this study were derived from 10,909 adult patients from the Inter-Agency Registry for Mechanically Assisted Circulatory Support (INTERMACS) who had a primary LVAD implanted between December 2006 and March 2014. An initial set of 176 pre-implantation variables were considered. RVF post-implant was categorized as acute ( 14 days) in onset. For each of these endpoints, a separate tree-augmented naive Bayes model was constructed using the most predictive variables employing an open source Bayesian inference engine. Results The acute RVF model consisted of 33 variables including systolic pulmonary artery pressure (PAP), white blood cell count, left ventricular ejection fraction, cardiac index, sodium levels, and lymphocyte percentage. The early RVF model consisted of 34 variables, including systolic PAP, pre-albumin, lactate dehydrogenase level, INTERMACS profile, right ventricular ejection fraction, pro-B-type natriuretic peptide, age, heart rate, tricuspid regurgitation, and body mass index. The late RVF model included 33 variables and was predicted mostly by peripheral vascular resistance, model for end-stage liver disease score, albumin level, lymphocyte percentage, and mean and diastolic PAP. The accuracy of all Bayesian models was between 91% and 97%, with an area under the receiver operator characteristics curve between 0.83 and 0.90, sensitivity of 90%, and specificity between 98% and 99%, significantly outperforming previously published risk scores. Conclusions A Bayesian prognostic model of RVF based on the large, multicenter INTERMACS registry provided highly accurate predictions of acute, early, and late RVF on the basis of pre-operative variables. These models may facilitate clinical decision making while screening candidates for LVAD therapy.