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Heart transplantation remains the gold standard treatment for end-stage heart failure patients without contraindications. However, limited donor availability and long wait times have created a need for left ventricular assist devices (LVAD) to be used as a bridge to transplantation in appropriately selected patients. Improvements in LVAD technology have resulted in improved short- and long-term outcomes, further supporting the use of these devices for a bridge-to-transplant (BTT) indication. LVAD utilization as BTT exhibits notable disparities worldwide, mainly due to variations in organ availability, allocation policies, and financial constraints. Although Europe has experienced a consistent increase in the use of LVAD for this purpose, the United Network for Organ Sharing 2018 policy amendment resulted in a significant reduction in the number of LVADs used for BTT in the US. To overcome this issue, modifications in the US allocation policy to consider factors such as days on device support, age, and type of complications may be necessary to potentially increase implantation rates.The authors provide an overview comparing the current state of heart transplantation in the US and Europe, with a particular focus on how distinct allocation policies and organ availability impact medical practices. Additionally, the review will examine critical aspects ranging from patient selection and pre-implantation optimization to post-transplant outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

The prevalence of end-stage heart failure and patients who could benefit from heart transplantation requires an expansion of the donor pool, relying on the transplant community to continually re-evaluate and expand the use of extended criteria donor organs. Introduction of new technologies such as the Paragonix SherpaPak Cardiac Transport System aids in this shift. We seek to analyze the impact of the SherpaPak system on recipient outcomes who receive extended criteria organs in the GUARDIAN-Heart Registry. Between October 2015 and December 2022, 1,113 adults from 15 US centers receiving donor hearts utilizing either SherpaPak (n = 560) or conventional ice storage (ice, n = 453) were analyzed from the GUARDIAN-Heart Registry using summary statistics. A previously published set of criteria was used to identify extended criteria donors, which included 193 SherpaPak and 137 ice. There were a few baseline differences among recipients in the 2 cohorts; most notably, IMPACT scores, distance traveled, and total ischemic time were significantly greater in SherpaPak, and significantly more donor hearts in the SherpaPak cohort had >4 hours total ischemia time. Posttransplant mechanical circulatory support utilization (SherpaPak 22.3% vs ice 35.0%, p = 0.012) and new extracorporeal membrane oxygenation/ventricular assist device (SherpaPak 7.8% vs ice 15.3%, p = 0.033) was significantly reduced, and the rate of severe primary graft dysfunction (SherpaPak 6.2% vs ice 13.9%, p = 0.022) was significantly reduced by over 50% in hearts preserved using SherpaPak. One-year survival between cohorts was similar (SherpaPak 92.9% vs ice 89.6%, p = 0.27). This subgroup analysis demonstrates that SherpaPak can be safely used to utilize extended criteria donors with low severe PGD rates. [ABSTRACT FROM AUTHOR]

Despite improving outcomes with modern pump technology, left ventricular assist device (LVAD) utilization for patients with end-stage heart failure (HF) has declined significantly in the preceding half-decade. Here, we examine this trend, noting an inherent contradiction in the declining utilization of an improving therapeutic option. We propose a series of provocative questions as a "call to action" for the field of advanced HF to consider both scientifically and clinically, focusing on our evaluation parameters for LVAD candidacy, our approach to dichotomous LVAD vs transplant decisions, and our current management paradigms. We conclude that modernization in these areas to match the advantages of modern pump technology is required to best serve patients with advanced HF. [ABSTRACT FROM AUTHOR]

Cardiovascular disease remains the leading cause of mortality in human immunodeficiency virus-infected (HIV-positive) patients. Ventricular assist device therapy is rarely offered to these patients and data on outcomes are sparse. We investigated outcomes following ventricular assist device implants for HIV-positive as compared to non-HIV-infected (HIV-negative) patients. We analyzed 22,065 patients from the Interagency Registry for Mechanically Assisted Circulatory Support registry for outcomes by HIV status. A propensity-matched analysis adjusting for 21 preimplant risk factors was also conducted. Compared with 21,980 HIV-negative device recipients, the 85 HIV-positive recipients were younger (median age 58 years vs 59 years, p = 0.02), had lower body mass index (26 kg/m2 vs 29 kg/m2, p = 0.001), and had higher rates of prior stroke (8% vs 4%, p = 0.02). In the matched HIV-positive and HIV-negative cohorts, there was significantly higher mortality in HIV-positive patients in earlier implant years, however, this association was not seen in later implant years (2018-2020). In both unmatched and matched cohorts, no significant differences in postimplantation stroke, major bleeding, or major infection were noted. With recent advancements in mechanical circulatory support and HIV treatment, ventricular assist device therapy is a viable therapeutic option for HIV-positive patients with end-stage heart failure. [ABSTRACT FROM AUTHOR]

Left ventricular assist devices (LVAD) provide circulatory blood pump support for severe heart failure patients. Pump inflow obstructions may lead to stroke and pump malfunction. We aimed to verify in vivo that gradual inflow obstructions, representing prepump thrombosis, are detectable by a pump-attached accelerometer, where the routine use of pump power (P LVAD) is deficient. In a porcine model (n = 8), balloon-tipped catheters obstructed HVAD inflow conduits by 34% to 94% in 5 levels. Afterload increases and speed alterations were conducted as controls. We computed nonharmonic amplitudes (NHA) of pump vibrations captured by the accelerometer for the analysis. Changes in NHA and P LVAD were tested by a pairwise nonparametric statistical test. Detection sensitivities and specificities were investigated by receiver operating characteristics with areas under the curves (AUC). NHA remained marginally affected during control interventions, unlike P LVAD. NHA elevated during obstructions within 52-83%, while mass pendulation was most pronounced. Meanwhile, P LVAD changed far less. Increased pump speeds tended to amplify the NHA elevations. The corresponding AUC was 0.85-1.00 for NHA and 0.35-0.73 for P LVAD. Elevated NHA provides a reliable indication of subclinical gradual inflow obstructions. The accelerometer can potentially supplement P LVAD for earlier warnings and localization of pump. [ABSTRACT FROM AUTHOR]

A redesigned surgically implanted heart pump incorporates several design changes from the prior device generation, but no published comparative data demonstrate if these changes translate to improved outcomes. We retrospectively compared clinical characteristics and outcomes, drawn from an FDA-mandated QA database, for contemporary patients treated with the Impella 5.5 or Impella 5.0 for acute myocardial infarction complicated by cardiogenic shock (AMICS), cardiomyopathy, or postcardiotomy cardiogenic shock (PCCS). A total of 1238 patients at 290 US sites were included for analysis. Patients receiving the Impella 5.5 had significantly higher survival through explant (i.e., successfully weaned or bridged to heart replacement therapy) than those receiving the Impella 5.0 in all 3 settings: AMICS (70.5% vs 56.8%; p = 0.005), cardiomyopathy (88.1% vs 76.9%; p = 0.001), and PCCS (76.1% vs 55.7%; p = 0.003). Duration of support was significantly longer for Impella 5.5 patients with AMICS (9.2 vs 6.1 days; p = 0.008) and cardiomyopathy (10.7 vs 8.1 days; p < 0.001). [ABSTRACT FROM AUTHOR]

Delayed sternal closure may be required after left ventricular assist device (LVAD) implantation due to coagulopathy or hemodynamic instability. There is conflicting data regarding infection risk. We performed a single-center, retrospective analysis of patients who received their first LVAD between May 2012 and January 2021. Patients were divided into delayed sternal closure (DSC) and primary sternal closure (PSC) groups. We used chi-squared or Fisher Exact tests, as appropriate, to compare the incidence of postoperative LVAD-related infections (mediastinal/sternal wound) and LVAD-specific infections (driveline and pump pocket) after definitive chest closure between these two groups. A total of 327 patients met eligibility criteria, including 127 (39%) patients that underwent DSC and 200 (61%) patients that had a PSC. Demographic and clinical characteristics were similar except for an overrepresentation of men (87% vs. 75%, p =.016), Interagency Registry of Mechanically Assisted Circulatory Support class I-II patients (89% vs 66%, p <.001), patients with a previous sternotomy (43% vs 13%, p <.001), and patients with chronic kidney disease (55% vs 43%, p =.030) in the DSC group. The median DSC time was 24 (IQR: 24-48) hours. The incidence of LVAD-related mediastinal/sternal wound infection was similar between the DSC and PSC groups (4.7% vs 3.0%, p =.419). There was no difference between DSC and PSC groups in the incidence of driveline infection (6.3% vs 9%, p =.411) and pump pocket infection (1.6% vs 1.5%, p =.901), respectively. DSC does not seem to increase the incidence of LVAD-related or LVAD-specific infection rates in heart failure patients undergoing device implantation surgery. [ABSTRACT FROM AUTHOR]

Heart transplantation (HT) remains the preferred therapy for patients with advanced heart failure. However, for sensitized HT candidates who have antibodies to human leukocyte antigens , finding a suitable donor can be challenging and can lead to adverse waitlist outcomes. In recent years, the number of sensitized patients awaiting HT has increased likely due to the use of durable and mechanical circulatory support as well as increasing number of candidates with underlying congenital heart disease. This State-of-the-Art review discusses the assessment of human leukocyte antigens antibodies, potential desensitization strategies including mechanisms of action and specific protocols, the approach to a potential donor including the use of complement-dependent cytotoxicity, flow cytometry, and virtual crossmatches, and peritransplant induction management. [ABSTRACT FROM AUTHOR]

Continuous flow left ventricular assist devices have improved outcomes in patients with end-stage heart failure that require mechanical circulatory support. Current devices have an adverse event profile that has hindered widespread application. The EVAHEART®2 left ventricular assist device (EVA2) has design features such as large blood gaps, lower pump speeds and an inflow cannula that does not protrude into the left ventricle that may mitigate the adverse events currently seen with other continuous flow devices. A prospective, multi-center randomized non-inferiority study, COMPETENCE Trial, is underway to assess non-inferiority of the EVA2 to the HeartMate 3 LVAS when used for the treatment of refractory advanced heart failure. The primary end-point is a composite of the individual primary outcomes: Survival to cardiac transplant or device explant for recovery; Free from disabling stroke; Free from severe Right Heart Failure after implantation of original device. Randomization is in a 2:1 (EVA2:HM3) ratio. The first patient was enrolled into the COMPETENCE Trial in December of 2020, and 25 subjects (16 EVA2 and 9 HM3) are currently enrolled. Enrollment of a safety cohort is projected to be completed by third quarter of 2022 at which time an interim analysis will be performed. Short-term cohort (92 EVA2 subjects) and long-term cohort is expected to be completed by the end of 2023 and 2024, respectively. The design features of the EVA2 such as a novel inflow cannula and large blood gaps may improve clinical outcomes but require further study. The ongoing COMPETENCE trial is designed to determine if the EVA2 is non-inferior to the HM3. [ABSTRACT FROM AUTHOR]

An unmet need exists for minimally invasive percutaneous mechanical circulatory support (pMCS) devices to provide partial support and promote cardiac rest and recovery in non–end-stage heart failure patients. This indication requires safe, long-term, ambulatory use with standard anticoagulation. The Aortix pump (Procyrion, Houston, Texas, USA) is a percutaneously deployed intra-aortic pump currently being clinically evaluated for subacute use and has the potential to provide extended therapy for non-end-stage heart failure patients. The device has demonstrated hemocompatibility and hemodynamic impact and has features well suited for home use. To evaluate the Aortix pump for long-term, ambulatory use, pumps were implanted in 4 untethered sheep. Pumps operated for 90 to 142 days and were stopped electively. Pump bearing components were found to have only superficial wear. No clinically significant hemolysis was observed and aorta and kidney histopathology showed no device-related findings or adhesions, suggesting Aortix is suitable for long-term (>6 months) ambulatory use. [ABSTRACT FROM AUTHOR]

The present study was designed to investigate the dynamics of right atrial pressure (RAP) and mid-regional pro-atrial natriuretic peptide (MR-proANP) during physical exercise in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to determine whether these parameters might serve as a tool to measure exercise-dependent atrial stress as an indicator of right heart failure. This prospective observational cohort study included 100 CTEPH patients who underwent right heart catheterization during physical exercise (eRHC). Blood samples for MR-proANP measurement were taken prior, during, and after eRHC. MR-proANP levels were correlated to RAP levels at rest, at peak exercise (eRAP), and during recovery. RAP at rest ≤7 mmHg was defined as normal and eRAP >15 mmHg as suggestive of right heart failure. During eRHC mean RAP increased from 6 mmHg (standard deviation, SD 4) to 16 mmHg (SD 7; p < 0.001). MR-proANP levels and dynamics correlated with RAP at rest (r s = 0.61; p < 0.001) and at peak exercise (r s = 0.66; p < 0.001). Logistic regression analysis revealed the peak MR-proANP level (B = 0.058; p = 0.004) and the right atrial area (B = 0.389; p < 0.001) to be associated with eRAP dynamics. A peak MR-proANP level ≥139 pmol/L (AUC = 0.81) and recovery level ≥159 pmol/L (AUC = 0.82) predicted an eRAP >15 mmHg. Physical exercise unmasked right heart failure in 39% of patients with normal RAP at rest; these patients were also characterized by a more distinct increase in MR-proANP levels (p = 0.005) and higher peak (p < 0.001) and recovery levels (p < 0.001). RAP and MR-proANP dynamics unmask manifest and latent right heart failure in CTEPH patients. [ABSTRACT FROM AUTHOR]

Left ventricular assist-device (LVAD) implantation is a life-saving therapy for patients with advanced heart failure (HF). With chronic unloading and circulatory support, LVAD-supported hearts often show significant reverse remodeling at the structural, cellular and molecular level. However, translation of these changes into meaningful cardiac recovery allowing LVAD explant is lagging. Part of the reason for this discrepancy is lack of anticipation and hence promotion and evaluation for recovery post LVAD implant. There is additional uncertainty about the long-term course of HF following LVAD explant. In selected patients, however, guided by the etiology of HF, duration of disease and other clinical factors, significant functional improvement and LVAD explantation with long-term freedom from recurrent HF events has been demonstrated to be feasible in a reproducible manner. The identified predictors of myocardial recovery suggest that the elective therapeutic use of potentially less invasive VADs for reversal of HF earlier in the disease process is a future goal that warrants further investigation. Hence, it is prudent to develop and implement tools to predict HF reversibility prior to LVAD implant, optimize unloading-promoted recovery with guideline directed medical therapy and monitor for myocardial improvement. This review article summarizes the clinical aspects of myocardial recovery and together with its companion review article focused on the biological aspects of recovery, they aim to provide a useful framework for clinicians and investigators. [ABSTRACT FROM AUTHOR]

Soluble Fms-like tyrosine kinase 1 (sFlt-1) may inhibit angiogenesis. Higher levels of sFlt-1 are associated with worse prognosis in prevalent heart failure patients. The aim of this study was to better understand the role of sFlt-1 in heart failure pathogenesis by characterizing relationships between sFlt-1, cardiac morphology, and the composite outcome of incident heart failure or cardiovascular (CV) death in in a multiethnic cohort free of CV disease at baseline. sFlt-1 was measured in 1,381 participants in the Multi-Ethnic Study of Atherosclerosis Angiogenesis sub-study. Linear regression was used to estimate the association between sFlt-1 and cardiac morphology and Cox proportional hazard regression was used to estimate associations with incident heart failure or CV mortality. Over a median follow-up of 13.1 years, higher sFlt-1 levels were associated with incident heart failure or CV mortality independent from CV risk factors or NT-proBNP levels (HR 1.17, 95% CI 1.10-1.26, p < 0.001). Higher sFlt-1 levels were also associated with greater baseline left ventricular (LV) mass by cardiac MRI and increased loss of LV mass over the 10 years following the baseline exam (p -value 0.02 for each), but this association was no longer statistically significant after adjustment for baseline NT-proBNP (p = 0.11 and 0.10 respectively). Baseline sFlt-1 levels are associated with incident heart failure and cardiovascular mortality independent of traditional CV risk factors or NT-proBNP. An association was also found with cardiac mass but was no longer significant after adjustment for NT-proBNP. [ABSTRACT FROM AUTHOR]

The clinical and cost-effectiveness of left ventricular assist device (LVAD) therapy for patients with advanced heart failure (HF) who are ineligible for heart transplantation is debated in the UK. This study develops an indirect comparison between the fully magnetically levitated HeartMate 3 (HM 3) LVAD and medical therapy (MT) to evaluate expected clinical and cost-effectiveness in the UK National Health Service (NHS) context. We performed an economic analysis comparing the HM3 pump against the HeartMate II LVAD (MOMENTUM 3), and then another analysis comparing MT with the first- and second-generation HeartMate XVE pump LVAD and HeartMate II LVAD for the same patient population (REMATCH and ROADMAP, respectively). By bridging those 2 analyses, an indirect comparison between HM3 and MT in the form of a network meta-analysis was developed. A literature search was performed to select the most appropriate pair of studies for this purpose. Outcomes were adjusted to produce Kaplan-Meier curves for the cost-effectiveness evaluation by using a decision-analytic model. Data were extrapolated linearly over a 5-year time horizon. Uncertainty and additional scenarios were addressed by one-way and probabilistic sensitivity analysis. Local costs and health utility were used from England, thereby representing the UK context. The incremental cost-effectiveness ratio (ICER) for LVAD vs MT in transplant ineligible patients with advanced HF was estimated to be £47,361 per quality-adjusted life year gained, with a 97.1% probability of being cost-effective at £50,000. In a subgroup of patients who are inotropic therapy dependent (INTERMACS 1-3 severity profile), the ICER was £45,616, while for a population with less-ill ambulatory HF (INTERMACS profile 4-7) the ICER changed to £64,051. This study provides evidence that HM3 LVAD therapy in advanced HF patients ineligible for heart transplantation may be cost-effective compared to MT in the NHS UK-England context. The ICER is lowest for patients dependent on inotropic support, but exceeds the willingness to pay threshold of £50,000 in ambulatory noninotropic therapy dependent advanced HF patients. [ABSTRACT FROM AUTHOR]

Continuous flow left ventricular assist devices (CF -LVAD) improve survival in patients with advanced heart failure, but confer risk of bleeding complications. Serotonergic antidepressants (SA) are commonly used in heart failure patients receiving LVADs, but their inhibitory effect on platelet function may contribute to bleeding risk. We performed a retrospective analysis of LVAD patients at our institution from 2016 –2019 comparing patients treated with SA after LVAD to those without SA. Demographic and clinical variables related to bleeding were collected on discharge from index hospitalization for CF-LVAD implantation and on admission for any bleeding event. The primary endpoint was incidence of bleeding requiring hospitalization after discharge. Secondary endpoints included overall number of admissions for bleeding, time to first hospitalization for a bleeding event, and incidence rate of hospitalizations for bleeding per patient year. 100 patients met inclusion criteria for the study. A total of 5 patients without a history of SA use and 31 patients who were prescribed SA after CF –LVAD implant were readmitted for a bleeding event after initial implant hospitalization (15% vs 46%, p = 0.004). Bleeding rate per person year (0.3 vs 0.61, p = 0.01) were significantly less in patients without SA use. Age-adjusted multivariable analysis found SA use to be associated with a hospitalization for bleeding (HR 2.3, 95% CI 0.99 –5.4). The higher incidence of hospitalization for bleeding was driven by non-gastrointestinal anatomical sites (6% vs 28%, p = 0.02) with a HR 7.7 (95% CI 0.96 –62). SA treatment after CF-LVAD implantation was associated with an increased risk for bleeding complications requiring hospitalization, particularly non-gastrointestinal bleeding. [ABSTRACT FROM AUTHOR]

There are limited safety data on reduced anti-thrombotic therapy (RT) in patients with HeartMate 3 (HM3) left ventricular assist device (LVAD). We conducted a single-center, retrospective study of patients with HM3 managed with RT from November 2014 through January 2020. We analyzed baseline characteristics, RT indications, and bleeding and thrombotic complications. We found that 50 of 161 patients with HM3 (31.1%) received RT starting at a median time of 90.5 days after LVAD implantation. Patients on RT were older and more likely to have ischemic heart failure than patients on standard anti-thrombotic therapy (ST). The most common indication for RT was gastrointestinal bleeding (29 patients [58.0%]). At 1-year follow-up, 5.0% of patients on RT developed a thrombotic event. Switching patients from ST to RT reduced the occurrence of major bleeding from 1.252 to 0.324 events per patient-year (p = 0.006). In our population of patients with HM3 LVAD, RT reduces bleeding without increasing the incidence of thrombosis. Our retrospective study suggests that an upfront RT strategy in patients with HM3 may be beneficial and should be prospectively studied. [ABSTRACT FROM AUTHOR]

Patients with continuous-flow left ventricular assist devices (CF-LVADs) experience limitations in functional capacity and frequently, right ventricular (RV) dysfunction. We sought to characterize RV function in the context of global cardiopulmonary performance during exercise in this population. A total of 26 patients with CF-LVAD (aged 58 ± 11 years, 23 males) completed a hemodynamic assessment with either conductance catheters (Group 1, n = 13) inserted into the right ventricle to generate RV pressure‒volume loops or traditional Swan‒Ganz catheters (Group 2, n = 13) during invasive cardiopulmonary exercise testing. Hemodynamics were collected at rest, 2 sub-maximal levels of exercise, and peak effort. Breath-by-breath gas exchange parameters were collected by indirect calorimetry. Group 1 participants also completed an invasive ramp test during supine rest to determine the impact of varying levels of CF-LVAD support on RV function. In Group 1, pump speed modulations minimally influenced RV function. During upright exercise, there were modest increases in RV contractility during sub-maximal exercise, but there were no appreciable increases at peak effort. Ventricular‒arterial coupling was preserved throughout the exercise. In Group 2, there were large increases in pulmonary arterial, left-sided filling, and right-sided filling pressures during sub-maximal and peak exercises. Among all participants, the cardiac output‒oxygen uptake relationship was preserved at 5.8:1. Ventilatory efficiency was severely abnormal at 42.3 ± 11.6. Patients with CF-LVAD suffer from limited RV contractile reserve; marked elevations in pulmonary, left-sided filling, and right-sided filling pressures during exercise; and severe ventilatory inefficiency. These findings explain mechanisms for persistent reductions in functional capacity in this patient population. [ABSTRACT FROM AUTHOR]

Frailty is prevalent in the patients with advanced heart failure; however, its impact on clinical outcomes after heart transplantation (HTx) is unclear. The aim of this study was to assess the impact of pre-transplant frailty on mortality and the duration of hospitalization after HTx. We retrospectively reviewed the post-transplant outcomes of 140 patients with advanced heart failure who had undergone frailty assessment within the 6-month interval before HTx: 43 of them were frail (F) and 97 were non-frail (NF). Post-transplant survival rates for the NF cohort at 1 and 12 months were 97% (93–100) and 95% (91–99) (95% CI), respectively. In contrast, post-transplant survival rates for the F cohort at the same time points were 86% (76–96) and 74% (60–84) (p < 0.0008 vs NF cohort), respectively. The Cox proportional hazards regression analysis demonstrated that pre-transplant frailty was an independent predictor of post-transplant mortality with a hazard ratio of 3.8 (95% CI: 1.4–10.5). Intensive care unit and hospital length of stay were 2 and 7 days longer in the F cohort (both p < 0.05), respectively, than in the NF cohort. Frailty within 6 months before HTx is independently associated with increased mortality and prolonged hospitalization after transplantation. Future research should focus on the development of strategies to mitigate the adverse effects of pre-transplant frailty. [ABSTRACT FROM AUTHOR]

Left ventricular assist device (LVAD) implantation is an established treatment for patients with advanced heart failure. To date, studies evaluating the impact of aerobic training in patients with LVADs have focused on moderate-intensity exercise. This pilot randomized controlled trial compared the effects of high-intensity interval training (HIIT) with those of moderate-intensity continuous training (MICT) on peak oxygen consumption (V̇O 2 peak) in patients with LVADs. Secondary outcomes included 6-minute walk test distance, flow-mediated dilation, and anthropometry. Assessments were conducted at baseline and after 12 weeks of supervised training performed 3 times weekly. Participants were randomized to HIIT (4 sets of 4 minutes at 80%–90% V̇O 2 reserve, alternating with 3 minutes at 50%–60% V̇O 2 reserve) or MICT groups (28 minutes continuously at 50%–60% V̇O 2 reserve). Within and between-group differences were analyzed using linear mixed models. Data are expressed as marginal means with 95% confidence intervals or as mean ± SD. A total of 21 participants were randomized (HIIT: age 57.7 ± 13.1 years; n = 11 and MICT: age 55.6 ± 14.2 years; n = 10) (mean ± SD). No major adverse events occurred in response to training in either group. HIIT significantly improved V̇O 2 peak (15.6 [13.2–17.8] to 18.4 [16.0–20.8] ml/kg/min) (marginal mean [95% CI]) compared with MICT (16.2 [13.8–18.7] to 17.2 [14.6–19.7] ml/kg/min; p < 0.05 between groups). No significant group differences were detected in secondary outcomes. In patients with LVADs, HIIT was well tolerated and increased aerobic capacity more than MICT. These preliminary findings support the prescription of high-intensity exercise in clinically stable patients with LVADs but warrant validation in a larger sample and across a broader range of physiologic and clinical outcomes. URL: https://www.anzctr.org.au , unique identifier: ACTRN12616001596493. [ABSTRACT FROM AUTHOR]

Combined heart–lung transplantation is the optimal treatment option for many patients with end-stage heart failure and fixed severe pulmonary hypertension. It offers the only possibility of long-term survival and a return to a normal quality of life. Unfortunately, it is rarely performed because of donor organ allocation policies. We present the case of a critically ill 24-year-old man, who after waiting for >100 days in-hospital on the urgent transplant list, deteriorated further and underwent the first successful heart–lung transplant with organs from a donation after circulatory death. [ABSTRACT FROM AUTHOR]

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. 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. 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%). 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. [ABSTRACT FROM AUTHOR]

Tricuspid regurgitation (TR) is common in patients with end-stage heart failure receiving left ventricular assist devices (LVADs), but the benefit of concomitant tricuspid valve procedures (TVPs) remains uncertain. This study examined the impact of TVP at the time of LVAD implantation on clinical outcomes and quality of life (QOL) metrics. We included adult patients in the Interagency Registry for Mechanical Circulatory Support database with various degrees of TR who received continuous-flow LVADs from 2008 to 2017. Patients undergoing concomitant TVP were compared with those without the intervention in a stratified analysis. Descriptive analyses, survival analyses, and Andersen‒Gill hazard models were used as appropriate to examine associations with clinical and patient-centered QOL outcomes. Our analysis included 8,263 (53.1%) mild, 4,252 (33.3%) moderate, and 2,100 (13.5%) severe TR cases. TVP rate increased with severity: 8.6% of mild, 18.0% of moderate, and 43.9% of severe cases. TVP was not associated with survival benefit in cases of mild (adjusted hazard ratio [aHR]: 0.97, 95% CI: 0.79–1.19, p = 0.75), moderate (aHR: 1.03, 95% CI: 0.88–1.20, p = 0.72), or severe (aHR: 1.20, 95% CI: 0.98–1.48, p = 0.08) TR. For patients with combined moderate or severe TR, TVP was associated with increased mortality (log-rank p < 0.01, aHR: 1.13, 95% CI: 1.00–1.27, p = 0.04). After adjusting for TR severity, TVP was associated with increased risk of bleeding, arrhythmia, and stroke (p < 0.01 each) and no improvements in QOL (p > 0.05). TVP at the time of LVAD implantation was not associated with either improved survival or QOL, and there were associations with increased risk of adverse events among patients with moderate and severe TR. [ABSTRACT FROM AUTHOR]

Gut microbial imbalance may contribute to endotoxemia, inflammation, and oxidative stress in heart failure (HF). Changes occurring in the intestinal microbiota and inflammatory/oxidative milieu during HF progression and following left ventricular assist device (LVAD) or heart transplantation (HT) are unknown. We aimed to investigate variation in gut microbiota and circulating biomarkers of endotoxemia, inflammation, and oxidative stress in patients with HF (New York Heart Association, Class I–IV), LVAD, and HT. We enrolled 452 patients. Biomarkers of endotoxemia (lipopolysaccharide and soluble [sCD14]), inflammation (C-reactive protein, interleukin-6, tumor necrosis factor-α, and endothelin-1 adiponectin), and oxidative stress (isoprostane) were measured in 644 blood samples. A total of 304 stool samples were analyzed using 16S rRNA sequencing. Gut microbial community measures of alpha diversity were progressively lower across worsening HF class and were similarly reduced in patients with LVAD and HT (p < 0.05). Inflammation and oxidative stress were elevated in patients with Class IV HF vs all other groups (all p < 0.05). Lipopolysaccharide was elevated in patients with Class IV HF (vs Class I–III) as well as in patients with LVAD and HT (p < 0.05). sCD14 was elevated in patients with Class IV HF and LVAD (vs Class I–III, p < 0.05) but not in patients with HT. Reduced gut microbial diversity and increased endotoxemia, inflammation, and oxidative stress are present in patients with Class IV HF. Inflammation and oxidative stress are lower among patients with LVAD and HT relative to patients with Class IV HF, whereas reduced gut diversity and endotoxemia persist in LVAD and HT. [ABSTRACT FROM AUTHOR]

The objectives of this study were to describe right ventricular-pulmonary arterial elastance coupling hemodynamic phenotypes and their frequency in patients with advanced heart failure and to evaluate the association of elastance-based indices with all-cause mortality, cardiac transplantation, and left ventricular assist device therapy. This study included 175 patients with heart failure undergoing right heart catheterization to evaluate candidacy for advanced therapies and 21 healthy controls. We modified a single-beat approach to elastance to account for the magnitude of pulmonary arterial pressure and estimated right ventricular end-systolic elastance (E es), pulmonary arterial elastance (E a), and the E es :E a ratio. We defined elevated pulmonary arterial load as an E a > 0.5 mm Hg/ml, and ventriculo-arterial uncoupling as an E es :E a < 0.8. We evaluated associations between E es , E a , and E es :E a with all-cause mortality and composite event-free survival using multivariable Cox proportional-hazard models, adjusted for age and sex. All 21 controls had E a ≤ 0.5 mm Hg/ml and E es :E a ≥ 0.8. Of 175 patients with heart failure, 63% had E a > 0.5 mm Hg/ml. E es :E a was lower in patients than in controls (p < 0.001), and 47% of the patients demonstrated E es :E a < 0.8, including 8% with normal E a. In median follow-up of 2.2 (0.8–4.6) years, 53 died, 37 received cardiac transplantation, and 33 received a left ventricular assist device. By multivariable analysis, E a (hazard ratios [HR]: 2.01, 95% CI 1.18–3.41) and E es :E a (HR: 0.46, 95% CI: 0.26–0.82) were independently associated with mortality, whereas E es was not. Right ventricular-pulmonary vascular coupling is frequently impaired in heart failure and associated with greater mortality. Elevated pulmonary arterial elastance is associated with greater mortality even when coupling is preserved. [ABSTRACT FROM AUTHOR]

Stroke is a leading cause of disability and death in advanced heart failure patients supported with a continuous-flow left ventricular assist system (CF-LVAS). Statins (HMG-CoA reductase inhibitors) reduce the risk of major cardiovascular and neurological events such as stroke, but their impact has not been evaluated in patients implanted with a CF-LVAS. We sought to explore the association between use of statin therapy and subsequent occurrence of neurological events, particularly stroke, following CF-LVAS implantation. We performed a single center, retrospective, observational cohort study in 200 consecutive adults implanted with a durable CF-LVAS over a 10-year period (2008-2018). We compared patients according to statin use following pump implantation, stratified by an exploratory analysis of pump type (HeartMate II, HeartWare HVAD, and HeartMate 3 [HM3] LVAS). Overall, 24% of CF-LVAS recipients developed at least 1 neurological event, at a rate of 0.11 events per patient-year (EPPY) among those prescribed statins and 0.22 EPPY among non-users (age-adjusted hazard ratio [HR] 0.46; 95% confidence interval [CI],0.24–0.88; p = 0.019). In the cohort without the HM3 pump, ischemic strokes were 62% lower among statin users (0.05 versus 0.12 EPPY for non-users; age-adjusted HR, 0.38; 95% CI, 0.15–0.99; p = 0.048). The risk of ischemic stroke did not differ significantly when HM3 recipients were included in the analysis (age-adjusted HR, 0.51; 95% CI, 0.22–1.21; p = 0.13). However, ischemic stroke rate in HM3 LVAS recipients was similar to the rate in statin users who received a non-HM3 LVAS (0.06 and 0.05 EPPY, respectively). Rates of hemorrhagic stroke and other safety end points were not significantly different according to statin use. Statin prescription following CF-LVAS is associated with lower rates of neurological events, driven predominantly by a reduction in ischemic strokes. These findings suggest that most patients with a pre-existing indication for statin therapy may continue using statins following CF-LVAS in an effort to decrease the incidence of ischemic stroke. [ABSTRACT FROM AUTHOR]

The potential impact of long-term left ventricular assist device (LVAD) support on the brain remains unclear. This study aimed to investigate cerebral microvascular damage in patients after long-term LVAD implantation using magnetic resonance imaging (MRI). We reviewed the medical records of patients after continuous-flow LVAD implantation in our hospital from 2006 to 2016, who underwent brain MRI after LVAD explantation for either transplantation or recovery. Age- and sex-matched healthy controls and patients with chronic heart failure (CHF) were collected from our pooled MRI database. The presence of cerebral microbleeds (CMBs) and cortical superficial siderosis and the severity of white matter hyperintensity (WMH) and cerebral atrophy were compared between patients with prior LVAD and 2 control groups. This study included 49 patients with prior LVAD, 49 healthy controls, and 45 patients with CHF. CMBs and cortical superficial siderosis were detected in 98% (p < 0.001) and 31% (p < 0.001) of patients with prior LVAD, respectively. The number of CMBs was higher in patients with prior LVAD than in the 2 control groups. The severity of the WMH was higher in patients with prior LVAD than in healthy controls but similar to that in patients with CHF. Quantitative analyses of cerebral atrophy revealed a significantly higher bicaudate ratio and cella media index in patients with prior LVAD than in the 2 control groups. Patients after long-term LVAD support showed a higher prevalence of CMBs and cortical superficial siderosis and more severe cerebral atrophy than did controls. These findings may indicate cerebral microvascular damages in long-term LVAD support patients. [ABSTRACT FROM AUTHOR]

Patients with advanced heart failure and cardiogenic shock (CS) often require temporary circulatory support (TCS) as a bridge to durable ventricular assist devices (dVADs). We aim to characterize longitudinal outcomes of patients with and without CS. Between 2013 and 2017, 13,813 adult patients classified as Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profiles 1 to 3 with continuous flow left ventricular assist devices or biventricular assist devices were registered into the International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support. Patients were sub-grouped according to support type (extracorporeal membrane oxygenation [ECMO], intra-aortic balloon pump [IABP], and other TCS). Other TCS included all other surgical and percutaneous TCS devices. Estimated survival was compared based on need for pre-operative TCS and by profile. Pre-operative TCS was used in 5,632 (41%) cases. Of these, ECMO was used in 1,138 (20%) cases, IABP in 3,901 (69%) cases, and other TCS in 595 (11%) cases. Patients requiring ECMO had greater needs for biventricular support after dVAD (22% ECMO, 5% IABP, and 7% other TCS; p < 0.001) with longer post-implant intensive care stays (ECMO 24 days, IABP 14 days, and other TCS 12 days; p < 0.001). INTERMACS Profile 1 to 3 patients with pre-implant ECMO had the lowest longitudinal survival (82% at 1 month and 44% at 48 months) compared with IABP (93% at 1 month and 51% at 48 months), other TCS (92% at 1 month and 52% at 48 months), and non-TCS (95% at 1 months and 55 % at 48 months) (p < 0.0001). Propensity score matching analysis of the pre-implant ECMO INTERMACS Profile 1 group when compared with alternative pre-implant TCS strategies had an associated higher hazard impacting early phase survival vs other TCS (hazard ratio, 1.80; p < 0.01) and IABP (hazard ratio, 1.65; p < 0.01). In advanced heart failure with patients with CS, the use of ECMO before dVAD was associated with lower longitudinal survival and increased utilization of biventricular support compared with alternative TCS strategies. Research focused on longitudinal profiling in CS and pre-implant TCS is warranted to further understand these differences. [ABSTRACT FROM AUTHOR]

Left ventricular assist devices (LVADs) have improved outcomes for selected patients with advanced heart failure, but alternative optimal surgical techniques remain to be defined. We aim to describe our initial experience in using a sternal-sparing (SS) technique for implantation of a magnetically levitated LVAD, the HeartMate 3 (HM3) pump. This retrospective, single-center study included consecutive patients implanted with the HM3 LVAD between September 2015 and September 2018. Patients were compared based on surgical approach: SS or traditional sternotomy (TS). The primary outcome was overall survival at 6 months. Secondary outcomes included peri-operative complications, blood product utilization, and hospital readmissions. Of 105 patients implanted with the HM3 LVAD, 41 (39%) were implanted via SS and 64 (61%) via TS approach. There were no intraoperative conversions. The SS patients were younger; otherwise, all other characteristics were similar between cohorts. The SS cohort demonstrated a significantly lower incidence of severe right ventricular failure (7% vs 28%, p = 0.012), fewer blood-product transfusions (41% vs 86%, p < 0.001), and shorter index hospital length of stay (15.5 vs 21 days, p = 0.018). Six-month survival was 93% for the SS cohort. In this single-center observational study, we have demonstrated that the SS approach may be a safe and effective surgical technique for implantation of the HM3 LVAD in well-selected patients. The potential benefits compared with TS require further inquiry. [ABSTRACT FROM AUTHOR]

Improved understanding of the clinical course of ambulatory advanced chronic systolic heart failure may improve the provision of appropriate care and is central to the design of clinical trials in this population. Twenty-one implanting ventricular assist device (VAD) centers enrolled 400 subjects in the Registry Evaluation of Vital Information for VADs in Ambulatory Life (REVIVAL), a prospective, observational study in ambulatory, chronic, advanced systolic heart failure, designed to identify a cohort with an approximately 25% 1-year risk of the primary composite outcome of death, urgent transplant, or durable mechanical circulatory support. Inclusion criteria utilized only information collected during routine clinical care. Exclusion criteria identified patients with contraindications to VAD. Study inclusion required at least 1 of 10 high-risk criteria derived from established hospitalization and non-hospitalization markers of increased mortality risk. We evaluated the test performance characteristics of the high-risk criteria. Data on 373 subjects evaluable for the primary composite outcome at the 1-year visit are presented. Baseline data were consistent with a less advanced cohort than Medical Arm for Mechanically Assisted Circulatory Support or Risk Assessment (MedaMACS) and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients (ROADMAP). Freedom from the primary composite outcome was 75.9%. Non-hospitalization inclusion criteria identified 89% of patients with events. Using routinely obtained clinical information for enrollment, REVIVAL successfully recruited an ambulatory chronic systolic heart failure cohort with an approximately 25% annual risk of the primary composite outcome. Information from this registry will be relevant to the planning of future trials of earlier VAD use and of other interventions in this population. [ABSTRACT FROM AUTHOR]

Ambulatory patients with advanced heart failure (HF) are often considered for advanced therapies, including durable mechanical circulatory support (MCS). The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles are a commonly used descriptor of disease severity in patients receiving MCS devices, but their role in defining the prognosis of ambulatory patients is less well established, especially for Profiles 6 and 7. Registry Evaluation of Vital Information on Ventricular Assist Devices in Ambulatory Life is a prospective observational study of 400 outpatients from 21 MCS and cardiac transplant centers. Eligible patients had New York Heart Association Class II to IV symptoms despite optimal medical and electrical therapies with a recent HF hospitalization, heart transplant listing, or evidence of high neurohormonal activation. The cohort included 33 INTERMACS Profile 4 (8%), 83 Profile 5 (21%), 155 Profile 6 (39%), and 129 Profile 7 (32%). Across INTERMACS profiles, there were no differences in age, gender, ejection fraction, blood pressure, or use of guideline-directed medical therapy. A lower INTERMACS profile was associated with more hospitalizations, greater frailty, and more impaired functional capacity and quality of life. The composite end point of death, durable MCS, or urgent transplant at 12 months occurred in 39%, 27%, 24%, and 14% subjects with INTERMACS Profiles 4, 5, 6, and 7, respectively (p = 0.004). Among ambulatory patients with advanced HF, a lower INTERMACS profile was associated with a greater burden of HF across multiple dimensions and a higher composite risk of durable MCS, urgent transplant, or death. These profiles may assist in risk assessment and triaging ambulatory patients to advanced therapies. [ABSTRACT FROM AUTHOR]

After 3 years of continuous-flow left ventricular assist device (CF-LVAD) support, nearly a third of patients develop at least moderate aortic insufficiency (AI). Percutaneous occluder devices, surgical aortic valve replacement (SAVR), and urgent heart transplantation are available treatment options. Transcatheter aortic valve replacement (TAVR) has not been widely used for treating symptomatic AI in patients on LVAD support. Retrospective chart review and data analysis from October 2010 through August 2017 was performed. A total of 286 patients with end-stage heart failure (ESHF) were implanted with a durable CF-LVAD. Nine patients subsequently developed significant symptomatic AI, which was treated with TAVR. All 9 patients had 1 TAVR procedure with resolution of AI and were discharged home. Procedural complications include valve migration warranting a second valve for stabilization, retroperitoneal and groin hematoma, and pseudoaneurysm requiring thrombin injection. A significant improvement of the New York Heart Association classification was noted from the time of implant to 6 months. Two patients had unplanned heart failure‒related hospitalizations within 6 months. At 6 months, 89% of patients were alive on LVAD support. TAVR is a successful treatment modality for LVAD patients who develop symptomatic AI. [ABSTRACT FROM AUTHOR]