Transplantation Outcomes with Donor Hearts after Circulatory Death.

BACKGROUND: Data showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited. METHODS: We conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation. RESULTS: A total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, -3 percentage points; 90% CI, -10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation. CONCLUSIONS: In this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.).

Dual-Organ Transplantation: Indications, Evaluation, and Outcomes for Heart-Kidney and Heart-Liver Transplantation: A Scientific Statement From the American Heart Association.

Although heart transplantation is the preferred therapy for appropriate patients with advanced heart failure, the presence of concomitant renal or hepatic dysfunction can pose a barrier to isolated heart transplantation. Because donor organ supply limits the availability of organ transplantation, appropriate allocation of this scarce resource is essential; thus, clear guidance for simultaneous heart-kidney transplantation and simultaneous heart-liver transplantation is urgently required. The purposes of this scientific statement are (1) to describe the impact of pretransplantation renal and hepatic dysfunction on posttransplantation outcomes; (2) to discuss the assessment of pretransplantation renal and hepatic dysfunction; (3) to provide an approach to patient selection for simultaneous heart-kidney transplantation and simultaneous heart-liver transplantation and posttransplantation management; and (4) to explore the ethics of multiorgan transplantation.

Inhaled Epoprostenol Compared With Nitric Oxide for Right Ventricular Support After Major Cardiac Surgery.

BACKGROUND: Right ventricular failure (RVF) is a leading driver of morbidity and death after major cardiac surgery for advanced heart failure, including orthotopic heart transplantation and left ventricular assist device implantation. Inhaled pulmonary-selective vasodilators, such as inhaled epoprostenol (iEPO) and nitric oxide (iNO), are essential therapeutics for the prevention and medical management of postoperative RVF. However, there is limited evidence from clinical trials to guide agent selection despite the significant cost considerations of iNO therapy. METHODS: In this double-blind trial, participants were stratified by assigned surgery and key preoperative prognostic features, then randomized to continuously receive either iEPO or iNO beginning at the time of separation from cardiopulmonary bypass with the continuation of treatment into the intensive care unit stay. The primary outcome was the composite RVF rate after both operations, defined after transplantation by the initiation of mechanical circulatory support for isolated RVF, and defined after left ventricular assist device implantation by moderate or severe right heart failure according to criteria from the Interagency Registry for Mechanically Assisted Circulatory Support. An equivalence margin of 15 percentage points was prespecified for between-group RVF risk difference. Secondary postoperative outcomes were assessed for treatment differences and included: mechanical ventilation duration; hospital and intensive care unit length of stay during the index hospitalization; acute kidney injury development including renal replacement therapy initiation; and death at 30 days, 90 days, and 1 year after surgery. RESULTS: Of 231 randomized participants who met eligibility at the time of surgery, 120 received iEPO, and 111 received iNO. Primary outcome occurred in 30 participants (25.0%) in the iEPO group and 25 participants (22.5%) in the iNO group, for a risk difference of 2.5 percentage points (two one-sided test 90% CI, -6.6% to 11.6%) in support of equivalence. There were no significant between-group differences for any of the measured postoperative secondary outcomes. CONCLUSIONS: Among patients undergoing major cardiac surgery for advanced heart failure, inhaled pulmonary-selective vasodilator treatment using iEPO was associated with similar risks for RVF development and development of other postoperative secondary outcomes compared with treatment using iNO. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03081052.

Surveillance and Alert-based Multiparameter Monitoring to Reduce Worsening Heart Failure Events: Results From SCALE-HF 1.

BACKGROUND: There is a need for better noninvasive remote monitoring solutions that prevent hospitalizations through the early prediction and management of heart failure (HF). SurveillanCe and Alert-Based Multiparameter Monitoring to ReducE Worsening Heart Failure Events (SCALE-HF 1) evaluated the performance of a novel congestion index that alerts to fluid accumulation preceding HF events. METHODS AND RESULTS: SCALE-HF 1 was a multicenter, prospective, observational study investigating HF event prediction using data from the cardiac scale. Participants with HF took measurements at home by standing barefoot on the scale for approximately 20 seconds each day. The congestion index was applied retrospectively, and an alert was generated when the index exceeded a fixed threshold established in prior studies. HF events were defined as unplanned administration of IV diuretics or admissions with a primary diagnosis of HF. Sensitivity was defined as the ratio of correctly identified HF events to the total number of HF events. We enrolled 329 participants (mean age 64 ± 14 years; 43% women; 32% Black; 56% with reduced ejection fraction) across 8 sites with 238 participant-years of follow-up and 69 usable HF events. The congestion index predicted 48 of the 69 HF events (70%) at 2.58 alerts per participant-year. In contrast, the standard weight rule (weight gain of >3 lb in 1 day or >5 lb in 7 days) predicted only 24 of the 69 HF events (35%) at 4.18 alerts per participant-year. The congestion index alerts had a significantly higher sensitivity (P < .01) at a lower alert rate than the standard weight rule. CONCLUSIONS: The congestion index alerts demonstrated sensitive prediction of HF events at a low alert rate, significantly exceeding the performance of weight-based monitoring. GOV IDENTIFIER: NCT04882449.

Medical Therapy Before, During and After Hospitalization in Medicare Beneficiaries With Heart Failure and Diabetes: Get With The Guidelines - Heart Failure Registry.

BACKGROUND: Patients hospitalized with heart failure (HF) and diabetes mellitus (DM) are at risk for worsening clinical status. Little is known about the frequency of therapeutic changes during hospitalization. We characterized the use of medical therapies before, during and after hospitalization in patients with HF and DM. METHODS: We identified Medicare beneficiaries in Get With The Guidelines-Heart Failure (GWTG-HF) hospitalized between July 2014 and September 2019 with Part D prescription coverage. We evaluated trends in the use of 7 classes of antihyperglycemic therapies (metformin, sulfonylureas, GLP-1RA, SGLT2-inhibitors, DPP-4 inhibitors, thiazolidinediones, and insulins) and 4 classes of HF therapies (evidence-based ß-blockers, ACEi or ARB, MRA, and ARNI). Medication fills were assessed at 6 and 3 months before hospitalization, at hospital discharge and at 3 months post-discharge. RESULTS: Among 35,165 Medicare beneficiaries, the median age was 77 years, 54% were women, and 76% were white; 11,660 (33%) had HFrEF (LVEF ≤ 40%), 3700 (11%) had HFmrEF (LVEF 41%-49%), and 19,805 (56%) had HFpEF (LVEF ≥ 50%). Overall, insulin was the most commonly prescribed antihyperglycemic after HF hospitalization (n = 12,919, 37%), followed by metformin (n = 7460, 21%) and sulfonylureas (n = 7030, 20%). GLP-1RA (n = 700, 2.0%) and SGLT2i (n = 287, 1.0%) use was low and did not improve over time. In patients with HFrEF, evidence-based beta-blocker, RASi, MRA, and ARNI fills during the 6 months preceding HF hospitalization were 63%, 62%, 19%, and 4%, respectively. Fills initially declined prior to hospitalization, but then rose from 3 months before hospitalization to discharge (beta-blocker: 56%-82%; RASi: 51%-57%, MRA: 15%-28%, ARNI: 3%-6%, triple therapy: 8%-20%; P < 0.01 for all). Prescription rates 3 months after hospitalization were similar to those at hospital discharge. CONCLUSIONS: In-hospital optimization of medical therapy in patients with HF and DM is common in participating hospitals of a large US quality improvement registry.

Remote Follow-up in a Heart Failure Pragmatic Trial: Insights From the CONNECT-HF.

BACKGROUND: Randomized controlled trials typically require study-specific visits, which can burden participants and sites. Remote follow-up, such as centralized call centers for participant-reported or site-reported, holds promise for reducing costs and enhancing the pragmatism of trials. In this secondary analysis of the CONNECT-HF (Care Optimization Through Patient and Hospital Engagement For HF) trial, we aimed to evaluate the completeness and validity of the remote follow-up process. METHODS AND RESULTS: The CONNECT-HF trial evaluated the effect of a post-discharge quality-improvement intervention for heart failure compared to usual care for up to 1 year. Suspected events were reported either by participants or by health care proxies through a centralized call center or by sites through medical-record queries. When potential hospitalization events were suspected, additional medical records were collected and adjudicated. Among 5942 potential hospitalizations, 18% were only participant-reported, 28% were reported by both participants and sites, and 50% were only site-reported. Concordance rates between the participant/site reports and adjudication for hospitalization were high: 87% participant-reported, 86% both, and 86% site-reported. Rates of adjudicated heart failure hospitalization events among adjudicated all-cause hospitalization were lower but also consistent: 45% participant-reported, 50% both, and 50% site-reported. CONCLUSIONS: Participant-only and site-only reports missed a substantial number of hospitalization events. We observed similar concordance between participant/site reports and adjudication for hospitalizations. Combining participant-reported and site-reported outcomes data is important to capture and validate hospitalizations effectively in pragmatic heart failure trials.

Novel Trial Designs in Heart Failure: Using Digital Health Tools to Increase Pragmatism.

PURPOSE OF REVIEW: Heart failure is an important clinical and public health issue. There is an urgent need to improve the efficiency of clinical trials in heart failure to rapidly identify new therapies and evidence-based implementation strategies for currently existing therapies. Electronic health (eHealth) platforms and digital health tools are being integrated into heart failure care. In this manuscript, we review opportunities to use these tools to potentially improve the design of and reduce the complexity of clinical trials in heart failure. RECENT FINDINGS: The PRECIS-2 tool outlines clinical trial design domains that are targets for pragmatism. We believe incorporating pragmatic design elements with the aid of eHealth platforms and digital health tools into clinical trials may help address the current complexity of clinical trials in heart failure and improve efficiency. In the manuscript, we provide examples from recent clinical trials across clinical trial design domains. We believe the current adoption of eHealth platforms and digital health tools is an opportunity improve the design of heart failure clinical trials. We specifically believe these tools can enhance pragmatism in clinical trials and reduce delays in generating high-quality evidence for new heart failure therapeutics.

Transthyretin amyloid cardiomyopathy among patients hospitalized for heart failure and performance of an adapted wild-type ATTR-CM machine learning model: Findings from GWTG-HF.

BACKGROUND: An 11-factor random forest model has been developed among ambulatory heart failure (HF) patients for identifying potential wild-type amyloidogenic TTR cardiomyopathy (wtATTR-CM). The model has not been evaluated in a large sample of patients hospitalized for HF. METHODS: This study included Medicare beneficiaries aged ≥65 years hospitalized for HF in the Get With The Guidelines-HF® Registry from 2008-2019. Patients with and without a diagnosis of ATTR-CM were compared, as defined by inpatient and outpatient claims data within 6 months pre- or post-index hospitalization. Within a cohort matched 1:1 by age and sex, univariable logistic regression was used to evaluate relationships between ATTR-CM and each of the 11 factors of the established model. Discrimination and calibration of the 11-factor model were assessed. RESULTS: Among 205,545 patients (median age 81 years) hospitalized for HF across 608 hospitals, 627 patients (0.31%) had a diagnosis code for ATTR-CM. Univariable analysis within the 1:1 matched cohort of each of the 11-factors in the ATTR-CM model found pericardial effusion, carpal tunnel syndrome, lumbar spinal stenosis, and elevated serum enzymes (e.g., troponin elevation) to be strongly associated with ATTR-CM. The 11-factor model showed modest discrimination (c-statistic 0.65) and good calibration within the matched cohort. CONCLUSIONS: Among US patients hospitalized for HF, the number of patients with ATTR-CM defined by diagnosis codes on an inpatient/outpatient claim within 6 months of admission was low. Most factors within the prior 11-factor model were associated with greater odds of ATTR-CM diagnosis. In this population, the ATTR-CM model demonstrated modest discrimination.

The Promise and Risks of mHealth in Heart Failure Care.

Mobile health (mHealth) is an emerging approach to health care. It involves wearable, connected technologies that facilitate patient-symptom or physiological monitoring, support clinical feedback to patients and physicians, and promote patients' education and self-care. Evolving algorithms may involve artificial intelligence and can assist in data aggregation and health care teams' interpretations. Ultimately, the goal is not merely to collect data; rather, it is to increase actionability. mHealth technology holds particular promise for patients with heart failure, especially those with frequently changing clinical status. mHealth, ideally, can identify care opportunities, anticipate clinical courses and augment providers' capacity to implement, titrate and monitor interventions safely, including evidence-based therapies. Although there have been marked advancements in the past decade, uncertainties remain for mHealth, including questions regarding optimal indications and acceptable payment models. In regard to mHealth capability, a better understanding is needed of the incremental benefit of mHealth data over usual care, the accuracy of specific mHealth data points in making clinical care decisions, and the efficiency and precision of algorithms used to dictate actions. Importantly, emerging regulations in the wake of COVID-19, and now the end of the federal public health emergency, offer both opportunity and risks to the broader adoption of mHealth-enabled services. In this review, we explore the current state of mHealth in heart failure, with particular attention to the opportunities and challenges this technology creates for patients, health care providers and other stakeholders.

LMNA Cardiomyopathy: Important Considerations for the Heart Failure Clinician.

BACKGROUND: A diagnosis of Lamin proteins A and C cardiomyopathy (LMNA-CM) not only impacts disease prognosis, but also leads to specific guideline-recommended treatment options for these patients. This etiology is fundamentally different from other genetic causes of dilated CM. METHODS AND RESULTS: LMNA-CM often presents early in the third to fourth decades and there is an age-dependent penetrance of nearly 90% among those with a positive genotype for LMNA-CM. Oftentimes, electrical abnormalities with either conduction disturbances and/or either atrial or ventricular arrhythmias manifest before there is imaging evidence of left ventricular dysfunction. Given these subtle early findings, cardiac magnetic resonance provides helpful guidance regarding patterns of enhancement associated with LMNA-CM, often before there is significant left ventricular dilation and/or a decrease in the ejection fraction and could be used for further understanding of risk stratification and prognosis of asymptomatic genotype-positive individuals. Among symptomatic patients with LMNA-CM, approximately one-quarter of individuals progress to needing advanced heart failure therapies such as heart transplantation. CONCLUSIONS: In the era of precision medicine, increased recognition of clinical findings associated with LMNA-CM and increased detection by genetic testing among patients with idiopathic nonischemic CM is of increasing importance. Not only does a diagnosis of LMNA-CM have implications for management and risk stratification, but new gene-based therapies continue to be evaluated for this group. Clinicians must be aware not only of the general indications for genetic testing in arrhythmogenic and dilated cardiomyopathies and of when to suspect LMNA-CM, but also of the clinical trials underway targeted toward the different genetic cardiomyopathies.

The Association Between Beta-blocker and Renin-Angiotensin System Inhibitor Use After Heart Failure With Reduced Ejection Fraction Hospitalization and Outcomes in Older Patients.

INTRODUCTION: Beta-blockers (BB) and renin-angiotensin system inhibitors (RASi) are foundational for the treatment of heart failure with reduced ejection fraction (HFrEF). However, given the increased risk of side effects in older patients, uncertainty remains as to whether, on net, older patients benefit as much as the younger patients studied in trials. METHODS AND RESULTS: Using the Get With The Guidelines-Heart Failure registry linked with Medicare data, overlap propensity weighted Cox proportional hazard models were used to examine the association between BB and RASi use at hospital discharge and 30-day and 1-year outcomes among patients with HFrEF. Among the 48,711 patients (aged ≥65 years) hospitalized with HFrEF, there were significant associations between BB and/or RASi use at discharge and lower rates of 30-day and 1-year mortality, including those over age 85 (30-day hazard ratio 0.56, 95% confidence interval 0.45-0.70; 1-year hazard ratio 0.69, 95% confidence interval 0.61-0.78). In addition, the magnitude of benefit associated with BB and/or RASi use after discharge did not decrease with advancing age. Even among the oldest patients, those over age 85, with hypotension, renal insufficiency or frailty, BB and/or RASi use at discharge was still associated with lower 1-year mortality or readmission. CONCLUSIONS: Among older patients hospitalized with HFrEF, BB and/or RASi use at discharge is associated with lower rates of 30-day and 1-year mortality across all age groups and the magnitude of this benefit does not seem to decrease with advancing age. These data suggest that, absent a clinical contraindication, BB and RASi should be considered in all patients hospitalized with HFrEF before or at hospital discharge, regardless of age.

Beyond Stage C: Considerations in the Management of Patients With Heart Failure Progression and Gaps in Evidence.

Despite treatment with contemporary medical therapies for chronic heart failure (HF), there has been an increase in the prevalence of patients progressing to more advanced disease. Patients progressing to and living at the interface of severe stage C and stage D HF are underrepresented in clinical trials, and there is a lack of high-quality evidence to guide clinical decision making. For patients with severe HF phenotypes, the medical therapies used for patients with less advanced stages of illness are often no longer tolerated or provide inadequate clinical stability. The limited data on these patients highlights the need to increase formal research characterizing this high-risk population. This review summarizes existing clinical trial data and incorporates our considerations for approaches to the medical management of patients advanced "beyond stage C" HF.

Variation in Hemodynamic Assessment and Interpretation: A Call to Standardize the Right Heart Catheterization.

BACKGROUND: Invasive hemodynamic measurement via right heart catheterization has shown divergent data in its role in the treatment of patients with heart failure (HF) and cardiogenic shock. We hypothesized that variation in data acquisition technique and interpretation might contribute to these observations. We sought to assess differences in hemodynamic acquisition and interpretation by operator subspecialty as well as level of experience. METHODS AND RESULTS: Individual-level responses to how physicians both collect and interpret hemodynamic data at the time of right heart catheterization was solicited via a survey distributed to international professional societies in HF and interventional cardiology. Data were stratified both by operator subspecialty (HF specialists or interventional cardiologists [IC]) and operator experience (early career [≤10 years from training] or late career [>10 years from training]) to determine variations in clinical practice. For the sensitivity analysis, we also look at differences in each subgroup. A total of 261 responses were received. There were 141 clinicians (52%) who self-identified as HF specialists, 99 (38%) identified as IC, and 20 (8%) identified as other. There were 142 early career providers (54%) and late career providers (119 [46%]). When recording hemodynamic values, there was considerable variation in practice patterns, regardless of subspecialty or level of experience for the majority of the intracardiac variables. There was no agreement or mild agreement among HF and IC as to when to record right atrial pressures or pulmonary capillary wedge pressures. HF cardiologists were more likely to routinely measure both Fick and thermodilution cardiac output compared with IC (51% vs 29%, P < .001), something mirrored in early career vs later career cardiologists. CONCLUSIONS: Significant variation exists between the acquisition and interpretation of right heart catheterization measurements between HF and IC, as well as those early and late in their careers. With the growth of the heart team approach to management of patients in cardiogenic shock, standardization of both assessment and management practices is needed.

Improved Outcomes in Severe Primary Graft Dysfunction After Heart Transplantation Following Donation After Circulatory Death Compared With Donation After Brain Death.

BACKGROUND: Primary graft dysfunction (PGD), the leading cause of early mortality after heart transplantation, is more common following donation after circulatory death (DCD) than donation after brain death (DBD). We conducted a single-center, retrospective cohort study to compare the incidence, severity and outcomes of patients experiencing PGD after DCD compared to DBD heart transplantation. METHODS AND RESULTS: Medical records were reviewed for all adult heart transplant recipients at our institution between March 2016 and December 2021. PGD was diagnosed within 24 hours after transplant according to modified International Society for Heart and Lung Transplant criteria. A total of 459 patients underwent isolated heart transplantation during the study period, 65 (14%) following DCD and 394 (86%) following DBD. The incidence of moderate or severe PGD in DCD and DBD recipients was 34% and 23%, respectively (P = 0.070). DCD recipients were more likely to experience severe biventricular PGD than DBD recipients (19% vs 7.4%; P = 0.004). Among patients with severe PGD, DCD recipients experienced shorter median (Q1, Q3) duration of post-transplant mechanical circulatory support (6 [4, 7] vs 9 [5, 14] days; P = 0.039), shorter median post-transplant hospital length of stay (17 [15, 29] vs 52 [26, 83] days; P = 0.004), and similar 60-day survival rates (100% [95% CI: 76.8%-100%] vs 80.0% [63.1%-91.6%]; P = 0.17) and overall survival (log-rank; P = 0.078) compared with DBD recipients. CONCLUSIONS: DCD heart transplant recipients were more likely to experience severe, biventricular PGD than DBD recipients. Despite this, DCD recipients with severe PGD spent fewer days on mechanical circulatory support and in the hospital than similar DBD patients. These findings suggest that patterns of graft dysfunction and recovery may differ between donor types, and they support the expansion of the heart-donor pool with DCD.

The association with organ procurement techniques and early cardiac transplant outcomes using cardiac MRI.

BACKGROUND: Heart transplantation (HT) has historically been limited by organ availability. Use of donation after circulatory death (DCD) donors addresses this limitation by utilizing previously unused hearts through use of the Organ Care System (OCS). OBJECTIVES: This study aimed to determine the impact of procurement and transportation method on allograft structure and function using early post-transplant cardiac magnetic resonance imaging (MRI). METHODS: Patients who underwent HT at our institution from February 1, 2020, through April 30, 2021 who underwent cardiac MRI imaging <60 days from transplant were included. Recipient and donor characteristics, clinical outcomes, and MRI findings were compared between those who underwent DCD transplantation using the OCS device (DCD-OCS), brain dead donation (DBD) using the OCS device (DBD-OCS), and DBD transported via cold storage (DBD-cold storage) using one-way analysis of variance. RESULTS: A total of 85 patients underwent HT with a cardiac MRI during the study period. Thirty-one (36%) patients received a DCD organ, 16 (19%) received a DBD-OCS organ and 38 (45%) received a DBD-cold storage organ. Rates of primary graft dysfunction (PGD) were significantly higher in DCD transplants (19.5% DCD vs. .0% DBD-OCS and 5.3% DBD-cold storage; p < .050 across three groups), but with no differences in mortality or rejection. There were no differences in cardiac MRI findings between the three transplant types, including presence of gadolinium hyperenhancement after transplant (all p > .050). CONCLUSIONS: We observed no differences in early cardiac MRI findings between patients that received DCD and DBD-OCS heart transplants compared with those receiving DBD-cold storage transplants.

Health care resource utilization and clinical outcomes for adult heart transplant recipients with primary graft dysfunction.

INTRODUCTION: The advent of new technologies to reduce primary graft dysfunction (PGD) and improve outcomes after heart transplantation are costly. Adoption of these technologies requires a better understanding of health care utilization, specifically the costs related to PGD. METHODS: Records were examined from all adult patients who underwent orthotopic heart transplantation (OHT) between July 1, 2013 and July 30, 2019 at a single institution. Total costs were categorized into variable, fixed, direct, and indirect costs. Patient costs from time of transplantation to hospital discharge were transformed with the z-score transformation and modeled in a linear regression model, adjusted for potential confounders and in-hospital mortality. The quintile of patient costs was modeled using a proportional odds model, adjusted for confounders and in-hospital mortality. RESULTS: 359 patients were analyzed, including 142 with PGD and 217 without PGD. PGD was associated with a .42 increase in z-score of total patient costs (95% CI: .22-.62; p < .0001). Additionally, any grade of PGD was associated with a 2.95 increase in odds for a higher cost of transplant (95% CI: 1.94-4.46, p < .0001). These differences were substantially greater when PGD was categorized as severe. Similar results were obtained for fixed, variable, direct, and indirect costs. CONCLUSIONS: PGD after OHT impacts morbidity, mortality, and health care utilization. We found that PGD after OHT results in a significant increase in total patient costs. This increase was substantially higher if the PGD was severe. SUMMARY: Primary graft dysfunction after heart transplantation impacts morbidity, mortality, and health care utilization. PGD after OHT is costly and investments should be made to reduce the burden of PGD after OHT to improve patient outcomes.

Multicenter study of universal prophylaxis versus pre-emptive therapy for patients at intermediate risk (R+) for CMV following heart transplantation.

INTRODUCTION: Heart transplant (HT) recipients with prior exposure to cytomegalovirus (CMV R+) are considered intermediate risk for CMV-related complications. Consensus guidelines allow for either universal prophylaxis (UP) or preemptive therapy (PET) (serial CMV testing) approaches to CMV prevention in such patients. Whether an optimal approach to mitigate CMV related risks exists in this setting remains uncertain. We therefore assessed the utility of PET as compared to UP in CMV R+ HT recipients. METHODS: Retrospective analysis of all CMV R+ HT recipients from 6 U.S. centers between 2010 and 2018 was performed. The primary outcome was the development of CMV DNAemia or end-organ disease resulting in the initiation/escalation of anti-CMV therapy. The secondary outcome was CMV-related hospitalization. Additional outcomes included incidence of acute cellular rejection (ACR) ≥ grade 2R, death, cardiac allograft vasculopathy (CAV), and leukopenia. RESULTS: Of 563 CMV R+ HT recipients, 344 (61.1%) received UP. PET was associated with increased risk for the primary (adjusted HR 3.95, 95% CI: 2.65-5.88, p < .001) and secondary (adjusted HR 3.19, 95% CI: 1.47-6.94, p = .004) outcomes, and with increased ACR ≥ grade 2R (PET 59.4% vs. UP 34.4%, p < .001). Incidence of detectable CAV was similar at 1 year (PET 8.2% vs. UP 9.5%, p = .698). UP was associated with increased incidence of leukopenia within 6 months post-HT (PET 34.7% vs. UP 43.6%, p = .036). CONCLUSION: The use of a PET CMV prophylaxis strategy in intermediate risk HT recipients associated with increased risk of CMV infection and CMV-related hospitalization, and may associate with worse post-HT graft outcomes.

Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure.

BACKGROUND: Acute decompensated heart failure accounts for more than 1 million hospitalizations in the United States annually. Whether the initiation of sacubitril-valsartan therapy is safe and effective among patients who are hospitalized for acute decompensated heart failure is unknown. METHODS: We enrolled patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure at 129 sites in the United States. After hemodynamic stabilization, patients were randomly assigned to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or enalapril (target dose, 10 mg twice daily). The primary efficacy outcome was the time-averaged proportional change in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration from baseline through weeks 4 and 8. Key safety outcomes were the rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema. RESULTS: Of the 881 patients who underwent randomization, 440 were assigned to receive sacubitril-valsartan and 441 to receive enalapril. The time-averaged reduction in the NT-proBNP concentration was significantly greater in the sacubitril-valsartan group than in the enalapril group; the ratio of the geometric mean of values obtained at weeks 4 and 8 to the baseline value was 0.53 in the sacubitril-valsartan group as compared with 0.75 in the enalapril group (percent change, -46.7% vs. -25.3%; ratio of change with sacubitril-valsartan vs. enalapril, 0.71; 95% confidence interval [CI], 0.63 to 0.81; P<0.001). The greater reduction in the NT-proBNP concentration with sacubitril-valsartan than with enalapril was evident as early as week 1 (ratio of change, 0.76; 95% CI, 0.69 to 0.85). The rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups. CONCLUSIONS: Among patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure, the initiation of sacubitril-valsartan therapy led to a greater reduction in the NT-proBNP concentration than enalapril therapy. Rates of worsening renal function, hyperkalemia, symptomatic hypotension, and angioedema did not differ significantly between the two groups. (Funded by Novartis; PIONEER-HF ClinicalTrials.gov number, NCT02554890 .).

Clinical trajectory of patients with a worsening heart failure event and reduced ventricular ejection fraction.

BACKGROUND: Recent data suggest that patients with heart failure with reduced ejection fraction (HFrEF) and worsening heart failure (WHF) have potential for greater benefit from newer HF therapies. We investigated characteristics and outcomes of patients with HFrEF and WHF by severity of left ventricular dysfunction. METHODS: We identified patients with chronic symptomatic HFrEF (left ventricular ejection fraction [LVEF] ≤35%) and evidence of WHF (emergency department visit or hospitalization for acute HF within 12 months of index echocardiogram) treated at Duke University between 1/2009 and 12/2018. Patients were stratified by LVEF≤25% or 26% to35%. Cox models were used to estimate cause-specific hazard ratios and 5-year event incidence of death and hospitalization across the range of LVEF. RESULTS: Of 2823 patients with HFrEF and WHF, 1620 (57.4%) had an LVEF≤25% and 1203 (42.6%) had an LVEF 26% to35%. Compared to patients with LVEF 26% to35%, those with LVEF≤25% were younger and more commonly men with a lower cardiovascular comorbidity burden. Patients with LVEF≤25% were less commonly on beta blockers (85.9% vs 90.5%) but more commonly treated with mineralocorticoid receptor antagonists (49.3% vs 41.1%) and implantable defibrillators (41.3% vs 28.2%). Patients with LVEF≤25% had significantly higher hazards for death (HR 1.24 [95% CI 1.11 - 1.38]), all-cause hospitalization (HR 1.21 [95% CI 1.10 - 1.33]), and HF hospitalization (HR 1.25 [95% CI 1.1 - 1.38]) through 5-years. CONCLUSIONS: More than half of patients with chronic HFrEF and WHF have severe LV dysfunction. Important differences in comorbidities, HF therapies, and outcomes exist between those with LVEF≤25% and those with LVEF 26% to35%.

Is the affordable care act medicaid expansion associated with receipt of heart failure guideline-directed medical therapy by race and ethnicity?

BACKGROUND: Uninsurance is a known contributor to racial/ethnic health inequities. Insurance is often needed for prescriptions and follow-up appointments. Therefore, we determined whether the Affordable Care Act(ACA) Medicaid Expansion was associated with increased receipt of guideline-directed medical treatment(GDMT) at discharge among patients hospitalized with heart failure(HF) by race/ethnicity. METHODS: Using Get With The Guidelines-HF registry, logistic regression was used to assess odds of receiving GDMT(HF medications; education; follow-up appointment) in early vs non-adopter states before(2012 - 2013) and after ACA Medicaid Expansion(2014 - 2019) within each race/ethnicity, accounting for patient-level covariates and within-hospital clustering. We tested for an interaction(p-int) between GDMT and pre/post Medicaid Expansion time periods. RESULTS: Among 271,606 patients(57.5% early adopter, 42.5% non-adopter), 65.5% were White, 22.8% African American, 8.9% Hispanic, and 2.9% Asian race/ethnicity. Independent of ACA timing, Hispanic patients were more likely to receive all GDMT for residing in early adopter states compared to non-adopter states (P <.0001). In fully-adjusted analyses, ACA Medicaid Expansion was associated with higher odds of receipt of ACEI/ARB/ARNI in Hispanic patients [before ACA:OR 0.40(95%CI:0.13,1.23); after ACA:OR 2.46(1.10,5.51); P-int = .0002], but this occurred in the setting of an immediate decline in prescribing patterns, particularly among non-adopter states, followed by an increase that remained lowest in non-adopter states. The ACA was not associated with receipt of GDMT for other racial/ethnic groups. CONCLUSIONS: Among GWTG-HF hospitals, Hispanic patients were more likely to receive all GDMT if they resided in early adopter states rather than non-adopter states, independent of ACA Medicaid Expansion timing. ACA implementation was only associated with higher odds of receipt of ACEI/ARB/ARNI in Hispanic patients. Additional steps are needed for improved GDMT delivery for all.