Stakeholders' perspectives on transplant metrics: the 2022 Scientific Registry of Transplant Recipients' consensus conference.

In July 2022, the Scientific Registry of Transplant Recipients (SRTR) hosted an innovative, multistakeholder consensus conference to identify information and metrics desired by stakeholders in the transplantation system, including patients, living donors, caregivers, deceased donor family members, transplant professionals, organ procurement organization professionals, payers, and regulators. Crucially, patients, caregivers, living donors, and deceased donor family members were included in all aspects of this conference, including serving on the planning committee, participating in preconference focus groups and learning sessions, speaking at the conference, moderating conference sessions and breakout groups, and shaping the conclusions. Patients constituted 24% of the meeting participants. In this report, we document the proceedings and enumerate 160 recommendations, 10 of which have been highly prioritized. SRTR will use the recommendations to develop new presentations of information and metrics requested by stakeholders to support informed decision-making.

Standardization of the Right Heart Catheterization and the Emerging Role of Advanced Hemodynamics in Heart Failure.

The accurate assessment of hemodynamics is paramount to providing timely and efficacious care for patients presenting in cardiogenic shock. Recently, the regular use of the pulmonary artery catheter in cardiogenic shock has had a resurgence with emerging data indicating improved survival in the modern era. Optimal multidisciplinary management of advanced heart failure and cardiogenic shock relies on our ability to effectively communicate and understand the complete hemodynamic assessment. Standardization of data acquisition and a renewed focus on the physiological processes, and thresholds driving disease progression, including the coupling ratio and myocardial reserve, are needed to fully understand and interpret the hemodynamic assessment. This State-of-the-Art review discusses best practices in the cardiac catheterization laboratory as well as emerging data on the prognostic role of emerging advanced hemodynamic parameters.

Physiology and Clinical Utility of HeartMate Pump Parameters.

The HeartMate 3 left ventricular assist device (LVAD) is now the only centrifugal pump intended for durable support being actively manufactured and implanted for adults in the United States. The changes in preload and afterload that accompany common clinical scenarios experienced by patients with an LVAD will cause specific changes to the LVAD pump parameters, namely, the pump power, pulsatility index, and flow. Appropriate care of this unique, and growing, population requires a full understanding of these variables as well as the underlying physiologic principles governing their derivation. The aim of this review is to focus on the updated functionality of the HeartMate 3, specifically in comparison to the HeartMate II, as well as the application of pump parameter interpretation to common clinical scenarios.

Improved Prognostic Performance of Cardiac Power Output With Right Atrial Pressure: A Subanalysis of the ESCAPE Trial.

BACKGROUND: The initial derivation of cardiac power output (CPO) included the difference between mean arterial pressure (MAP) and right atrial pressure (RAP) in the numerator, before multiplying by cardiac output (CO). We hypothesized that the inclusion of RAP (CPO-RAP) would enhance the prognostic performance of this parameter in those with an elevated RAP. METHODS AND RESULTS: We obtained patient-level data from the ESCAPE trial via the Biolincc database. Participants with full final hemodynamics were included in the analysis. The CPO-RAP was calculated as [(MAP - RAP) × CO)]/451 Watts (W), and the CPO was calculated as (MAP × CO)/451. The primary outcome was freedom from left ventricular assist device, heart transplant, or death at 6 months. Included participants (n = 157) were a median of 58 years of age (interquartile range [IQR] 49-67 years), 27% were women, and 59% had ischemic cardiomyopathy. The median CPO was 0.70 W (IQR 0.50-0.90 W), and the median CPO-RAP was 0.62 W (IQR 0.47-0.79 W). In univariable logistic regressions, the CPO was not associated with the primary outcome (odds ratio 0.32, 95% confidence interval 0.08-1.29, P = .11), but the CPO-RAP was (odds ratio 0.10, 95% confidence interval 0.02-0.54, P < .01). In Kaplan-Meier analyses, there were no significant difference in outcomes with CPO (76% vs 64%, P = .08), but for CPO-RAP, there were significant differences in outcomes (81% vs 63%, P = .01). When further delineating CPO-RAP by RAP above or below the median, there was no significant difference in the outcome for participants with a RAP 8 or less (94% vs 79%, P = .07), but a significant difference in participants with a RAP of more than 8 mm Hg (66% vs 45%, P < .05). CONCLUSIONS: The inclusion of RAP resulted in a significant association with the primary outcome; CPO alone was not.

Center Variability in Patient Outcomes Following HeartMate 3 Implantation: An Analysis of the MOMENTUM 3 Trial.

BACKGROUND: As left ventricular assist device (LVAD) survival rates continue to improve, evaluating site-specific variability in outcomes can facilitate identifying targets for quality-improvement initiative opportunities in the field. METHODS: Deidentified center-specific outcomes were analyzed for HeartMate 3 (HM3) patients enrolled in the MOMENTUM 3 pivotal and continued access protocol trials. Centers < 25th percentile for HM3 volumes were excluded. Variability in risk-adjusted center mortality was assessed at 90 days and 2 years (conditional upon 90-day survival). Adverse event (AE) rates were compared across centers. RESULTS: In the 48 included centers (1958 patients), study-implant volumes ranged between 17 and 106 HM3s. Despite similar trial-inclusion criteria, patient demographics varied across sites, including age quartile ((Q)1-Q3:57-62 years), sex (73%-85% male), destination therapy intent (60%-84%), and INTERMACS profile 1-2 (16%-48%). Center mortality was highly variable, nadiring at ≤ 3.6% (≤ 25th percentile) and peaking at ≥ 10.4% (≥ 75th percentile) at 90 days and ≤ 10.2% and ≥ 18.7%, respectively, at 2 years. Centers with low mortality rates tended to have lower 2-year AE rates, but no center was a top performer for all AEs studied. CONCLUSIONS: Mortality and AEs were highly variable across MOMENTUM 3 centers. Studies are needed to improve our understanding of the drivers of outcome variability and to ascertain best practices associated with high-performing centers across the continuum of intraoperative to chronic stages of LVAD support.

Postoperative tolvaptan use in left ventricular assist device patients: The TOLVAD randomized pilot study.

PURPOSE: Tolvaptan, a selective vasopressin type-2 antagonist, has been shown to increase serum sodium (Na) and urine output in hyponatremic left ventricular assist device (LVAD) patients in retrospective studies. In this prospective randomized pilot study, we aimed to assess the efficacy of tolvaptan in this population. METHODS: We conducted a prospective, randomized, non-blinded pilot study of LVAD recipients with post-operative hyponatremia (Na < 135 mEq/L) (NCT05408104). Eligible participants were randomized to receive tolvaptan 15 mg daily in addition to usual care versus usual care alone. The primary outcome was a change in Na level and estimated glomerular filtration rate (eGFR), from the first post-operative day of hyponatremia (the day of randomization) to discharge. RESULTS: A total of 33 participants were enrolled, and 28 underwent randomization (median age 55 [IQR 50-62]), 21% women, 54% Black, 32% ischemic cardiomyopathy, median baseline Na 135 (IQR 134-138). Fifteen participants were randomized to tolvaptan (TLV) and 13 were randomized to usual care alone (No-TLV). Mean change in Na from randomization to discharge in the TLV group was 2.7 mEq/L (95%CI 0.7-4.7, p = 0.013) and 1.8 (95%CI 0.5-4.0, p = 0.11) in the No-TLV group, though baseline and final Na levels were similar between groups. The mean change in eGFR was 2.6 ml/min/1.73 m2 (95%CI 10.1-15.3, p = 0.59) in TLV versus 7.5 ml/min/1.73 m2 (95%CI 5.2-20.2, p = 0.15) in No-TLV. TLV participants had significantly more urine output than No-TLV patients during their first 24 h after randomization (3294 vs 2155 ml, p = 0.043). CONCLUSION: TLV significantly increases urine output, with nominal improvement in Na level, in hyponatremic post-operative LVAD patients without adversely impacting renal function.

Value of Hemodynamic Monitoring in Patients With Cardiogenic Shock Undergoing Mechanical Circulatory Support.

The recent widespread availability and use of mechanical circulatory support is transforming the management and outcomes of cardiogenic shock (CS). Clinical decision-making regarding the optimization of therapies for patients with CS can be guided effectively by hemodynamic monitoring with a pulmonary artery catheter (PAC). Because several studies regarding the benefit of PACs are ambiguous, the use of PACs is variable among clinicians treating patients with CS. More notable is that PAC use has not been studied as part of a randomized, controlled trial in patients with CS with or without mechanical circulatory support. Standardized approaches to hemodynamic monitoring in these patients can improve decision-making and outcomes. In this review, we summarize the hemodynamics of CS and mechanical circulatory support with PAC-derived measurements, and provide a compelling rationale for the use of PAC monitoring in patients with CS receiving mechanical circulatory support.

Non-Concordance between Patient and Clinician Estimates of Prognosis in Advanced Heart Failure.

IMPORTANCE: Despite efforts to enhance serious illness communication, patients with advanced heart failure (HF) lack prognostic understanding. OBJECTIVES: To determine rate of concordance between HF patients' estimation of their prognosis and their physician's estimate of the patient's prognosis, and to compare patient characteristics associated with concordance. DESIGN: Cross-sectional analysis of a cluster randomized controlled trial with 24-month follow-up and analysis completed on 09/01/2020. Patients were enrolled in inpatient and outpatient settings between September 2011 to February 2016 and data collection continued until the last quarter of 2017. SETTING: Six teaching hospitals in the U.S. PARTICIPANTS: Patients with advanced HF and implantable cardioverter defibrillators (ICDs) at high risk of death. Of 537 patients in the parent study, 407 had complete data for this analysis. INTERVENTION: A multi-component communication intervention on conversations between HF clinicians and their patients regarding ICD deactivation and advance care planning. MAIN OUTCOME(S) AND MEASURE(S): Patient self-report of prognosis and physician response to the "surprise question" of 12-month prognosis. Patient-physician prognostic concordance (PPPC) measured in percentage agreement and kappa. Bivariate analyses of characteristics of patients with and without PPPC. RESULTS: Among 407 patients (mean age 62.1 years, 29.5% female, 42.4% non-white), 300 (73.7%) dyads had non-PPPC; of which 252 (84.0%) reported a prognosis >1 year when their physician estimated <1 year. Only 107 (26.3%) had PPPC with prognosis of ≤ 1 year (n=20 patients) or > 1 year (n=87 patients); (Κ = -0.20, p = 1.0). Of those with physician estimated prognosis of < 1 year, non-PPPC was more likely among patients with lower symptom burden- number and severity (both p ≤.001), without completed advance directive (p=.001). Among those with physician prognosis estimate > 1 year, no patient characteristic was associated with PPPC or non-PPPC. CONCLUSIONS AND RELEVANCE: Non-PPPC between HF patients and their physicians is high. HF patients are more optimistic than clinicians in estimating life expectancy. These data demonstrate there are opportunities to improve the quality of prognosis disclosure between patients with advanced HF and their physicians. Interventions to improve PPPC might include serious illness communication training.

Aortic Pulsatility Index: A Novel Hemodynamic Variable for Evaluation of Decompensated Heart Failure.

BACKGROUND: Right heart catheterization for invasive hemodynamics has shown only modest correlation with clinical outcomes. We designed a novel hemodynamic variable that incorporates ventricular output and filling pressure. We anticipated that the aortic pulsatility index (API) would correlate with clinical outcomes in patients with heart failure. METHODS AND RESULTS: We retrospectively analyzed consecutive patients undergoing right heart catheterization with milrinone drug study at our institution (February 2013 to November 2019). The API was calculated as (systolic blood pressure - diastolic blood pressure)/pulmonary capillary wedge pressure. The primary outcome was freedom from advanced therapies, defined as the need for inotropes, temporary mechanical circulatory support, a left ventricular assist device, or orthotopic heart transplantation, or death at 30 days. A total of 224 patient encounters, age 57 years (48-66 years; 34% women; 31% ischemic cardiomyopathy) were included. In univariable analysis, lower baseline API was significantly associated with progression to advanced therapies or death at 30-days (odds ratio 0.43, 95% confidence interval 0.30-0.61; P < .001) compared with those on continued medical management. Receiver operator characteristic analysis specified an optimal cutpoint of 1.45 for API. A Kaplan-Meier analysis indicated an association of API with the primary outcome (79% for API ≥ 1.45 vs 48% for API < 1.45). In multivariable analysis, higher API was strongly associated with freedom from advanced therapies or death (odds ratio 0.38, 95% confidence interval 0.22-0.65, P ≤ .001), even when adjusted for baseline characteristics and routine right heart catheterization measurements. CONCLUSIONS: The API is a novel invasive hemodynamic measurement that is associated independently with freedom from advanced therapies or death at 30-day follow-up.

HFSA/SAEM/ISHLT Clinical Expert Consensus Document on the Emergency Management of Patients with Ventricular Assist Devices.

Mechanical circulatory support is now widely accepted as a viable long-term treatment option for patients with end-stage heart failure (HF). As the range of indications for the implantation of ventricular assist devices grows, so does the number of patients living in the community with durable support. Because of their underlying disease and comorbidities, in addition to the presence of mechanical support, these patients are at a high risk for medical urgencies and emergencies (Table 1). Thus, it is the responsibility of clinicians to understand the basics of their emergency care. This consensus document represents a collaborative effort by the Heart Failure Society of America, the Society for Academic Emergency Medicine, and the International Society for Heart and Lung Transplantation (ISHLT) to educate practicing clinicians about the emergency management of patients with ventricular assist devices. The target audience includes HF specialists and emergency medicine physicians, as well as general cardiologists and community-based providers.

Rationale and Design of the EMPA-TROPISM Trial (ATRU-4): Are the "Cardiac Benefits" of Empagliflozin Independent of its Hypoglycemic Activity?

The SGLT2 inhibitor empagliflozin reduced cardiovascular mortality by 38% and heart failure (HF) hospitalizations by 35% in diabetic patients. We have recently demonstrated the efficacy of empagliflozin in ameliorating HF and improving cardiac function in a non-diabetic porcine model of HF mediated via a switch in myocardial metabolism that enhances cardiac energetics. Therefore, we hypothesized that the cardiac benefits of empagliflozin can also be extended to non-diabetic HF patients. The EMPA-TROPISM clinical trial is a randomized, double-blind, parallel group, placebo-controlled, trial comparing the efficacy of and safety of empagliflozin in non-diabetic HF patients. Eighty patients with stable HF for over 3 months, LVEF < 50%, and New York Heart Association functional class II to IV symptoms will be randomized to empagliflozin 10 mg for 6 months or placebo. All patients will undergo cardiac magnetic resonance (CMR), cardiopulmonary exercise test (CPET), 6-min walk test, and quality of life questionnaires. The primary outcome is the change in left ventricular end-diastolic volume measured by CMR. Secondary end-points include change in peak VO2 (CPET); change in LV mass, in LVEF, in myocardial mechanics (strains), in left atrium volumes, in RV function and volumes, in interstitial myocardial fibrosis, and in epicardial adipose tissue (CMR); change in the distance in the 6-min walk test; and changes in quality of life (Kansas Cardiomyopathy questionnaire [KCCQ-12] and the 36-Item Short Form Survey [SF-36]). Safety issues (e.g., hypoglycemia, urinary infections, ketoacidosis,…) will also be monitored. In summary, EMPA-TROPISM clinical trial will determine whether the SGLT2 inhibitor empagliflozin improves cardiac function and heart failure parameters in non-diabetic HF patients (EMPA-TROPISM [ATRU-4]: Are the "cardiac benefits" of Empagliflozin independent of its hypoglycemic activity; NCT 03485222).

Three-dimensional echocardiography demonstrates a skewered left ventricular thrombus in a patient with a heart transplant.

A left ventricular (LV) false tendon is a frequently visualized structure in echocardiography with unclear clinical significance. We present the case of a false tendon serving as a nidus for thrombus in a post-orthotopic heart transplantation patient. Three-dimensional transthoracic echocardiography (3DTTE) was utilized to visualize a LV mass and facilitate its identification as a thrombus as well as the surrounding structures. Using datasets from 3DTTE, the lack of ventricular wall attachment and circumferential formation of the thrombus around the false tendon was identified. Serial imaging demonstrated resolution of the thrombus with anticoagulation.

Left Ventricular Assist Devices: The Adolescence of a Disruptive Technology.

Clinical outcomes for patients with advanced heart failure receiving left ventricular assist devices are driven by appropriate patient selection, refined surgical technique, and coordinated medical care. Perhaps even more important is innovative pump design. The introduction and widespread adoption of continuous-flow ventricular assist devices has led to a paradigm shift within the field of mechanical circulatory support, making the promise of lifetime device therapy closer to reality. The disruption caused by this new technology, on the one hand, produced meaningful improvements in patient survival and quality of life, but also introduced new clinical challenges, such as bleeding, pump thrombosis, and acquired valvular heart disease. Further evolution within this field will require financial investment to sustain innovation leading to a fully implantable, durable, and cost-effective pump for a larger segment of patients with advanced heart failure.

Clinical variability within the INTERMACS 1 profile: implications for treatment options.

PURPOSE OF REVIEW: The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) I classification encompasses patients with varying clinical presentations and prognoses. The purpose of this review is to discuss four sub-classifications of cardiogenic shock patients (acute myocardial infarction, acute decompensated heart failure, biventricular failure, and myocarditis), and explore management considerations for these groups, with particular emphasis on strategies for device placement. RECENT FINDINGS: In single-center studies, the use of intra-aortic balloon counterpulsation, percutaneous ventricular assist devices, and extra-corporeal membrane oxygenation (ECMO) has allowed approximately half of cardiogenic shock patients to receive an implantable left ventricular assist device (LVAD) or heart transplant, or experience myocardial recovery. Primary implantation of a durable LVAD in well-selected myocardial infarction shock patients was associated with a 1-year survival of 86% in one small case series. Analysis of a multi-institutional database suggests patients older than 65 years have a lower post-implantation survival compared with younger recipients. SUMMARY: Device selection strategies for INTERMACS I patients are predicated on a patient's prognosis, hemodynamic stability, end organ, and neurologic status. Percutaneous assist devices may be preferred for patients with favorable prognoses, ECMO for patients with hemodynamic compromise, and durable mechanical support for patients failing to recover sustainable myocardial function after short-term device use.

SGLT2 Inhibitors, Functional Capacity, and Quality of Life in Patients With Heart Failure: A Systematic Review and Meta-Analysis.

Importance: The associations of sodium glucose cotransporter-2 inhibitors (SGLT2is) with reduction in mortality and hospitalization rates in patients with heart failure (HF) are well established. However, their association with improving functional capacity and quality of life (QOL) has been variably studied and less reported. Objective: To provide evidence on the extent to which SGLT2is are associated with improvement on objective measures of functional capacity and QOL in patients living with HF. Data Sources: The MEDLINE, EMBASE, and Cochrane databases were systematically searched for relevant articles on July 31, 2023. Study Selection: Randomized, placebo-controlled clinical trials reporting the effect of SGLT2i on functional outcomes of exercise capacity (peak oxygen consumption [peak VO2] or 6-minute walk distance [6MWD]) and/or QOL using validated questionnaires for patients with HF were included. Data Extraction and Synthesis: Data were extracted by 2 authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, and a meta-analysis using the restricted maximum likelihood random-effects model was conducted. Main Outcomes and Measures: Outcomes of interest included changes in peak VO2, 6MWD, and Kansas City Cardiomyopathy Questionnaire-12 total symptom score (KCCQ-TSS), clinical summary score (KCCQ-CSS), and overall summary score (KCCQ-OSS). Results: In this meta-analysis of 17 studies, 23 523 patients (mean [range] age, 69 [60-75] years) were followed over a period ranging from 12 to 52 weeks. Four studies included peak VO2 as an outcome, 7 studies included 6MWD, and 10 studies reported KCCQ scores. Mean (SD) left ventricular ejection fraction was 43.5% (12.4%). Compared with controls, patients receiving SGLT2i treatment experienced significant increases in peak VO2 (mean difference [MD], 1.61 mL/kg/min; 95% CI, 0.59-2.63 mL/kg/min; P = .002) and 6MWD (MD, 13.09 m; 95% CI, 1.20-24.97 m; P = .03). SGLT2i use was associated with increased KCCQ-TSS (MD, 2.28 points; 95% CI, 1.74-2.81 points; P < .001), KCCQ-CSS (MD, 2.14 points; 95% CI, 1.53-2.74 points; P < .001), and KCCQ-OSS (MD, 1.90 points; 95% CI, 1.41-2.39 points; P < .001) scores. Subgroup analysis and meta-regression demonstrated almost all improvements were consistent across ejection fraction, sex, and the presence of diabetes. Conclusions and Relevance: These findings suggest that in addition to known clinical associations with mortality and hospitalization outcomes, SGLT2i use is associated with improvement in outcomes of interest to patients' everyday lives as measured by objective assessments of maximal exercise capacity and validated QOL questionnaires, regardless of sex or ejection fraction.

Incidence, Outcomes, and Opportunity for Left Ventricular Assist Device Weaning for Myocardial Recovery.

BACKGROUND: Myocardial recovery occurs in patients with advanced heart failure on left ventricular assist device (LVAD) support, but there is the premise that it is rare with uncertain results. OBJECTIVES: The goal of this study was to investigate the incidence and consequence of LVAD explant after myocardial recovery. METHODS: Using the United Network for Organ Sharing registry, LVAD implants in the United States between 2005 and 2020 were tracked until death, transplantation, or explant for myocardial recovery. The cohort undergoing explant was followed up for heart failure relapse (defined as relisting followed by delisting due to death, being too ill, or transplantation; or second durable LVAD implant). RESULTS: Of 15,728 LVAD implants, 126 patients underwent explant for recovery, which only occurred in 55 (38%) of 145 implanting centers. The crude cumulative incidence was 0.7% at 2 years, whereas the incidence reached 4.7% among designated centers in the selected young nonischemic cohort. Of 126 explanted patients, 76 (60%) were subsequently delisted for sustained recovery. Heart failure relapsing had a relatively higher hazard in the early phase, with a 30-day incidence of 6% (7 of 126) but tapered following with the freedom rate of 72.5% at 4 years. CONCLUSIONS: In the United States, LVAD explant for myocardial recovery was underutilized, leading to a very low incidence at the national level despite a realistic rate being achieved in designated centers for selected patients. With follow-up extending up to 4 years after explant, more than one-half were successfully removed and stayed off the waitlist, and approximately 70% were free from heart failure relapse events.

Remote Dielectric Sensing Before and After Discharge in Patients With ADHF: The ReDS-SAFE HF Trial.

BACKGROUND: Incomplete treatment of congestion often leads to worsening heart failure (HF). The remote dielectric sensing (ReDS) system is an electromagnetic energy-based technology that accurately quantifies changes in lung fluid concentration noninvasively. OBJECTIVES: This study sought to assess whether an ReDS-guided strategy during acutely decompensated HF hospitalization is superior to routine care for improving outcomes at 1 month postdischarge. METHODS: ReDS-SAFE HF (Use of ReDS for a SAFE discharge in patients with acute Heart Failure) was an investigator-initiated, multicenter, single-blind, randomized, proof-of-concept trial in which 100 patients were randomized to a routine care strategy, with discharge criteria based on current clinical practice, or an ReDS-guided decongestion strategy, with discharge criteria requiring an ReDS value of ≤35%. ReDS measurements were performed daily and at a 7-day follow-up visit, with patients and treating physicians in the routine care arm blinded to the results. The primary outcome was a composite of unplanned visits for HF, HF rehospitalization, or death at 1 month after discharge. RESULTS: The mean age was 67 ± 14 years, and 74% were male. On admission, left ventricular ejection fraction was 37% ± 16%, and B-type natriuretic peptide was 940 pg/L (Q1-Q3: 529-1,665 pg/L). The primary endpoint occurred in 10 (20%) patients in the routine care group and 1 (2%) in the ReDS-guided strategy group (log-rank P = 0.005). The ReDS-guided strategy group experienced a lower event rate, with an HR of 0.094 (95% CI: 0.012-0.731; P = 0.003), and a number of patients needed to treat of 6 to avoid an event (95% CI: 3-17), mainly resulting from a decrease in HF readmissions. The median length of stay was 2 days longer in the ReDS-guided group vs the routine care group (8 vs 6; P = 0.203). CONCLUSIONS: A ReDS-guided strategy to treat congestion improved 1-month prognosis postdischarge in this proof-of-concept study, mainly because of a decrease of the number of HF readmissions. (Use of ReDS for a SAFE discharge in patients with acute Heart Failure [ReDS-SAFE HF]; NCT04305717).