Polypharmacy in Palliative Care for Advanced Heart Failure: The PAL-HF Experience.

BACKGROUND: Palliative care (PC) in advanced heart failure (HF) aims to improve symptoms and quality of life (QOL), in part through medication management. The impact of PC on polypharmacy (>5 medications) remains unknown. METHODS AND RESULTS: We explored patterns of polypharmacy in the Palliative Care in HF (PAL-HF) randomized controlled trial of standard care vs interdisciplinary PC in advanced HF (N = 150). We describe differences in medication counts between arms at 2, 6, 12, and 24 weeks for HF (12 classes) and PC (6 classes) medications. General linear mixed models were used to evaluate associations between treatment arm and polypharmacy over time. The median age of the patients was 72 years (interquartile range 62-80 years), 47% were female, and 41% were Black. Overall, 48% had ischemic etiology, and 55% had an ejection fraction of 40% or less. Polypharmacy was present at baseline in 100% of patients. HF and PC medication counts increased in both arms, with no significant differences in counts by drug class at any time point between arms. CONCLUSIONS: In a trial of patients with advanced HF considered eligible for PC, polypharmacy was universal at baseline and increased during follow-up with no effect of the palliative intervention on medication counts relative to standard care.

SGLT-2 Inhibitors for Patients with Heart Failure: What Have We Learned Recently?

PURPOSE OF REVIEW: In this review, we discuss the mechanisms of action of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and the purported protective effects for mitigating heart failure (HF)-related outcomes. RECENT FINDINGS: Major randomized clinical trials have demonstrated the cardiovascular safety and efficacy of SGLT-2i among patients without known HF and those with established HF with reduced ejection fraction or preserved ejection fraction (HFrEF and HFpEF respectively). Recent HF guidelines have incorporated SGLT-2i in HF treatment algorithms. SGLT-2i have emerged as a novel treatment for both prevention of HF and reduction of cardiovascular morbidity and mortality among patients with existing HFrEF or HFpEF.

The Cost-Effectiveness of Palliative Care: Insights from the PAL-HF Trial.

BACKGROUND: In a randomized control trial, Palliative Care in Heart Failure (PAL-HF) improved heart failure-related quality of life, though cost-effectiveness remains unknown. The aim of this study was to evaluate the cost-effectiveness of the PAL-HF trial, which provided outpatient palliative care to patients with advanced heart failure. METHODS AND RESULTS: Outcomes for usual care and PAL-HF strategies were compared using a Markov cohort model over 36 months from a payer perspective. The model parameters were informed by PAL-HF trial data and supplemented with meta-analyses and Medicare administrative data. Outcomes included hospitalization, place of death, Medicare expenditures, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. Simulated mortality rates were the same for PAL-HF and usual care cohorts, at 89.7% at 36 months. In the base case analysis, the PAL-HF intervention resulted in an incremental gain of 0.03 QALYs and an incremental cost of $964 per patient for an incremental cost-effectiveness ratio of $29,041 per QALY. In 1-way sensitivity analyses, an intervention cost of up to $140 per month is cost effective at $50,000 per QALY. Of 1000 simulations, the PC intervention had a 66.1% probability of being cost effective at a $50,000 willingness-to-pay threshold assuming no decrease in hospitalization. In a scenario analysis, PAL-HF decreased payer spending through reductions in noncardiovascular hospitalizations. CONCLUSIONS: These results from this single-center trial are encouraging that palliative care for advanced heart failure is an economically attractive intervention. Confirmation of these findings in larger multicenter trials will be an important part of developing the evidence to support more widespread implementation of the PAL-HF palliative care intervention.

A change of heart: Preliminary results of the US 2018 adult heart allocation revision.

In 2018, the Organ Procurement and Transplantation Network (OPTN) modified adult heart allocation to better stratify candidates and provide broader access to the most medically urgent candidates. We analyzed OPTN data that included waiting list and transplant characteristics, geographical distribution, and early outcomes 1 year before (pre: October 18, 2017-October 17, 2018) and following (post: October 18, 2018-October 17, 2019) implementation. The number of adult heart transplants increased from 2954 pre- to 3032 postimplementation. Seventy-eight percent of transplants in the post era were for the most medically urgent (statuses 1-3) compared to 68% for status 1A in the pre era. The median distance between the donor hospital and transplant center increased from 83 to 216 nautical miles, with an increase in total ischemic time from 3 to 3.4 hours (all P < .001). Waiting list mortality was not different across eras (14.8 vs 14.9 deaths per 100 patient-years pre vs post respectively). Posttransplant patient survival was not different, 93.6% pre and 92.8% post. There is early evidence that the heart allocation policy has enhanced stratification of candidates by their medical urgency and broader distribution for the most medically urgent candidates with minimal impact on overall waiting list mortality and posttransplant outcomes.

Intrapericardial Left Ventricular Assist Device for Advanced Heart Failure.

BACKGROUND: Mechanical circulatory support with a left ventricular assist device (LVAD) is an established treatment for patients with advanced heart failure. We compared a newer LVAD design (a small intrapericardial centrifugal-flow device) against existing technology (a commercially available axial-flow device) in patients with advanced heart failure who were ineligible for heart transplantation. METHODS: We conducted a multicenter randomized trial involving 446 patients who were assigned, in a 2:1 ratio, to the study (centrifugal-flow) device or the control (axial-flow) device. Adults who met contemporary criteria for LVAD implantation for permanent use were eligible to participate in the trial. The primary end point was survival at 2 years free from disabling stroke or device removal for malfunction or failure. The trial was powered to show noninferiority with a margin of 15 percentage points. RESULTS: The intention-to treat-population included 297 participants assigned to the study device and 148 participants assigned to the control device. The primary end point was achieved in 164 patients in the study group and 85 patients in the control group. The analysis of the primary end point showed noninferiority of the study device relative to the control device (estimated success rates, 55.4% and 59.1%, respectively, calculated by the Weibull model; absolute difference, 3.7 percentage points; 95% upper confidence limit, 12.56 percentage points; P=0.01 for noninferiority). More patients in the control group than in the study group had device malfunction or device failure requiring replacement (16.2% vs. 8.8%), and more patients in the study group had strokes (29.7% vs. 12.1%). Quality of life and functional capacity improved to a similar degree in the two groups. CONCLUSIONS: In this trial involving patients with advanced heart failure who were ineligible for heart transplantation, a small, intrapericardial, centrifugal-flow LVAD was found to be noninferior to an axial-flow LVAD with respect to survival free from disabling stroke or device removal for malfunction or failure. (Funded by HeartWare; ENDURANCE ClinicalTrials.gov number, NCT01166347 .).

Virtual Visits for Care of Patients with Heart Failure in the Era of COVID-19: A Statement from the Heart Failure Society of America.

In response to the COVID-19 pandemic, US federal and state governments have implemented wide-ranging stay-at-home recommendations as a means to reduce spread of infection. As a consequence, many US healthcare systems and practices have curtailed ambulatory clinic visits-pillars of care for patients with heart failure (HF). In this context, synchronous audio/video interactions, also known as virtual visits (VVs), have emerged as an innovative and necessary alternative. This scientific statement outlines the benefits and challenges of VVs, enumerates changes in policy and reimbursement that have increased the feasibility of VVs during the COVID-19 era, describes platforms and models of care for VVs, and provides a vision for the future of VVs.

Variables of importance in the Scientific Registry of Transplant Recipients database predictive of heart transplant waitlist mortality.

The prelisting variables essential for creating an accurate heart transplant allocation score based on survival are unknown. To identify these we studied mortality of adults on the active heart transplant waiting list in the Scientific Registry of Transplant Recipients database from January 1, 2004 to August 31, 2015. There were 33 069 candidates awaiting heart transplantation: 7681 UNOS Status 1A, 13 027 Status 1B, and 12 361 Status 2. During a median waitlist follow-up of 4.3 months, 5514 candidates died. Variables of importance for waitlist mortality were identified by machine learning using Random Survival Forests. Strong correlates predicting survival were estimated glomerular filtration rate (eGFR), serum albumin, extracorporeal membrane oxygenation, ventricular assist device, mechanical ventilation, peak oxygen capacity, hemodynamics, inotrope support, and type of heart disease with less predictive variables including antiarrhythmic agents, history of stroke, vascular disease, prior malignancy, and prior tobacco use. Complex interactions were identified such as an additive risk in mortality based on renal function and serum albumin, and sex-differences in mortality when eGFR >40 mL/min/1.73 m. Most predictive variables for waitlist mortality are in the current tiered allocation system except for eGFR and serum albumin which have an additive risk and complex interactions.

Primary graft dysfunction after heart transplantation: Incidence, trends, and associated risk factors.

Changes in heart transplantation (HT) donor and recipient demographics may influence the incidence of primary graft dysfunction (PGD). We conducted a retrospective study to evaluate PGD incidence, trends, and associated risk factors by analyzing consecutive adult patients who underwent HT between January 2009 and December 2014 at our institution. Patients were categorized as having PGD using the International Society for Heart & Lung Transplantation (ISHLT)-defined criteria. Variables, including clinical and demographic characteristics of donors and recipients, were selected to assess their independent association with PGD. A time-trend analysis was performed over the study period. Three-hundred seventeen patients met inclusion criteria. Left ventricular PGD, right ventricular PGD, or both, were observed in 99 patients (31%). Risk factors independently associated with PGD included ischemic time, recipient African American race, and recipient amiodarone treatment. Over the study period, there was no change in the PGD incidence; however, there was an increase in the recipient pretransplantation use of amiodarone. The rate of 30-day mortality was significantly elevated in those with PGD versus those without PGD (6.06% vs 0.92%, P = .01). Despite recent advancements, incidence of PGD remains high. Understanding associated risk factors may allow for implementation of targeted therapeutic interventions.

Worsening renal function during decongestion among patients hospitalized for heart failure: Findings from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial.

INTRODUCTION: Worsening renal function (WRF) can occur throughout a hospitalization for acute heart failure (HF). However, decongestion can be measured in different ways and the prognostic implications of WRF in the setting of different measures of decongestion are unclear. METHODS: Patients (N = 433) from the ESCAPE were classified by measures of decongestion during hospitalization: hemodynamic (right atrial pressure ≤8 mmHg and/or wedge pressure ≤15 mmHg at discharge), clinical (≤1 sign of congestion at discharge), hemoconcentration (any increase in hemoglobin) and estimated plasma volume using the Hakim formula (5% reduction in plasma volume). WRF was defined as creatinine increase ≥0.3 mg/dl during hospitalization. The association between WRF and 180-day all-cause death was assessed. RESULTS: Successful decongestion was observed in 124 (60%) patients by hemodynamics, 204 (49%) by clinical exam, 173 (47%) by hemoconcentration, and 165 (45%) by plasma volume. There was no agreement between the hemodynamic assessment and other decongestion measures in up to 43% of cases. Persistent congestion with concomitant WRF at discharge was associated with worse outcomes compared to patients without congestion and WRF. Among patients decongested at discharge, in-hospital WRF was not significantly associated with 180-day all-cause death, when using hemodynamic, clinical or estimated plasma volume as measures of decongestion (P > .05 for all markers). CONCLUSIONS: In patients hospitalized for HF, although there was disagreement across common measures of decongestion, in-hospital WRF was not associated with increased hazard of all-cause mortality among patients successfully decongested at discharge.

Trends and outcomes of cardiac transplantation from donors dying of drug intoxication.

BACKGROUND: Deaths from drug intoxication have increased in the United States but outcomes of recipients of orthotopic heart transplantation (OHT) from these donors are not well characterized. METHODS: We performed a retrospective analysis of the United Network for Organ Sharing's STAR database between January 2000 and March 2014 and assessed mortality and retransplantation using adjusted Cox models by mechanism of donor death. RESULTS: Of the 31,660 OHTs from 2000 to 2014, 1233 (3.9%) were from drug intoxication. These donors were more likely to be female, white, with greater tobacco use and higher BMI compared to donors who died of other mechanisms. Drug intoxication accounted for 1.1% of OHT donors in 2000 and 6.2% in March 2014. No significant difference was observed in 10-year mortality (adjusted hazard ratio [HR], 95% confidence interval [CI]: 0.99, 0.87-1.13), 10-year retransplantation (adjusted HR 0.84, 0.49-1.41) or 1-year and 3-year rehospitalization with other mechanisms of death compared to drug intoxication. CONCLUSION: There has been a large increase in OHT donors who die of drug intoxication in the United States. OHT outcomes from these donors are similar to those dying from other mechanisms. These data have important implications for donor selection in context of the ongoing opioid epidemic.

Indications for and outcomes of therapeutic plasma exchange after cardiac transplantation: A single center retrospective study.

INTRODUCTION: Limited data are available describing indications for and outcomes of therapeutic plasma exchange (TPE) in cardiac transplantation. METHODS: In a retrospective study of patients who underwent cardiac transplantation at Duke University Medical Center from 2010 to 2014, we reviewed 3 TPE treatment patterns: a Single TPE procedure within 24 h of transplant; Multiple TPE procedures initiated within 24 h of transplant; and 1 or more TPE procedures beginning >24 h post-transplant. Primary and secondary outcomes were overall survival (OS) and TPE survival (TS), respectively. RESULTS: Of 313 patients meeting study criteria, 109 (35%) underwent TPE. TPE was initiated in 82 patients within 24 h, 40 (37%) receiving a single procedure (Single TPE), and 42 (38%) multiple procedures (Multiple TPE). Twenty-seven (25%) began TPE >24 h after transplant (Delayed TPE). The most common TPE indication was elevated/positive panel reactive or human leukocyte antigen antibodies (32%). With a median follow-up of 49 months, the non-TPE treated and Single TPE cohorts had similar OS (HR 1.08 [CI, 0.54, 2.14], P = .84), while the Multiple and Delayed TPE cohorts had worse OS (HR 2.62 [CI, 1.53, 4.49] and HR 1.98 [CI, 1.02, 3.83], respectively). The Multiple and Delayed TPE cohorts also had worse TS (HR 2.59 [CI, 1.31, 5.14] and HR 3.18 [CI, 1.56, 6.50], respectively). Infection rates did not differ between groups but was independently associated with OS (HR 2.31 [CI, 1.50, 3.54]). CONCLUSIONS: TPE is an important therapeutic modality in cardiac transplant patients. Prospective studies are needed to better define TPE's different roles in this patient population.

Unexpected abrupt increase in left ventricular assist device thrombosis.

BACKGROUND: We observed an apparent increase in the rate of device thrombosis among patients who received the HeartMate II left ventricular assist device, as compared with preapproval clinical-trial results and initial experience. We investigated the occurrence of pump thrombosis and elevated lactate dehydrogenase (LDH) levels, LDH levels presaging thrombosis (and associated hemolysis), and outcomes of different management strategies in a multi-institutional study. METHODS: We obtained data from 837 patients at three institutions, where 895 devices were implanted from 2004 through mid-2013; the mean (±SD) age of the patients was 55±14 years. The primary end point was confirmed pump thrombosis. Secondary end points were confirmed and suspected thrombosis, longitudinal LDH levels, and outcomes after pump thrombosis. RESULTS: A total of 72 pump thromboses were confirmed in 66 patients; an additional 36 thromboses in unique devices were suspected. Starting in approximately March 2011, the occurrence of confirmed pump thrombosis at 3 months after implantation increased from 2.2% (95% confidence interval [CI], 1.5 to 3.4) to 8.4% (95% CI, 5.0 to 13.9) by January 1, 2013. Before March 1, 2011, the median time from implantation to thrombosis was 18.6 months (95% CI, 0.5 to 52.7), and from March 2011 onward, it was 2.7 months (95% CI, 0.0 to 18.6). The occurrence of elevated LDH levels within 3 months after implantation mirrored that of thrombosis. Thrombosis was presaged by LDH levels that more than doubled, from 540 IU per liter to 1490 IU per liter, within the weeks before diagnosis. Thrombosis was managed by heart transplantation in 11 patients (1 patient died 31 days after transplantation) and by pump replacement in 21, with mortality equivalent to that among patients without thrombosis; among 40 thromboses in 40 patients who did not undergo transplantation or pump replacement, actuarial mortality was 48.2% (95% CI, 31.6 to 65.2) in the ensuing 6 months after pump thrombosis. CONCLUSIONS: The rate of pump thrombosis related to the use of the HeartMate II has been increasing at our centers and is associated with substantial morbidity and mortality.

Assessment of cardiac allograft systolic function by global longitudinal strain: From donor to recipient.

BACKGROUND: Cardiac allografts are routinely evaluated by left ventricular ejection fraction (LVEF) before and after transplantation. However, myocardial deformation analyses with LV global longitudinal strain (GLS) are more sensitive for detecting impaired LV myocardial systolic performance compared with LVEF. METHODS: We analyzed echocardiograms in 34 heart donor-recipient pairs transplanted at Duke University from 2000 to 2013. Assessments of allograft LV systolic function by LVEF and/or LV GLS were performed on echocardiograms obtained pre-explanation in donors and serially in corresponding recipients. RESULTS: Donors had a median LVEF of 55% (25th, 75th percentile, 54% to 60%). Median donor LV GLS was -14.6% (-13.7 to -17.3%); LV GLS was abnormal (ie, >-16%) in 68% of donors. Post-transplantation, LV GLS was further impaired at 6 weeks (median -11.8%; -11.0 to -13.4%) and 3 months (median -11.4%; -10.3 to -13.9%) before recovering to pretransplant levels in follow-up. Median LVEF remained ≥50% throughout follow-up. We found no association between donor LV GLS and post-transplant outcomes, including all-cause hospitalization and mortality. CONCLUSIONS: GLS demonstrates allograft LV systolic dysfunction in donors and recipients not detected by LVEF. The clinical implications of subclinical allograft dysfunction detected by LV GLS require further study.

Preoperative Determinants of Quality of Life and Functional Capacity Response to Left Ventricular Assist Device Therapy.

BACKGROUND: Left ventricular assist devices (LVADs) improve survival, quality of life (QOL), and functional capacity (FC) among patients with end-stage heart failure. Few data are available regarding characteristics associated with QOL and FC response. METHODS AND RESULTS: Patients enrolled in the Heartmate II clinical trials that were alive with ongoing LVAD support at 6 months were included. QOL response criteria included scoring above the lowest quartile on either the Minnesota Living With Heart Failure Questionnaire or the Kansas City Cardiomyopathy Questionnaire. FC responder criteria included improvement in 6-minute walk distance (6MWD) >70 meters from baseline, a 6MWD >220 meters at 6 months, or New York Heart Association functional class I or II. Independent variables associated with QOL nonresponse included history of diabetes (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.20-2.78), lower mean pulmonary arterial pressure (OR 0.97, 95% CI 0.95-0.99), or a Heartmate II right ventricular risk score >2 (OR 1.77, 95% CI 1.00-3.12). Variables associated with FC nonresponse included history of COPD (OR 1.92, 95% CI 1.22-3.03) or diabetes (OR 1.52, 95% CI 1.01-2.27). Compared with responders, QOL and FC nonresponders had reduced long-term survival. CONCLUSIONS: Preoperative comorbidities, including diabetes, COPD, and right heart failure, may limit the QOL and FC response to LVAD therapy and should be considered during the shared decision-making process.

Elevated Cardiac Troponin I in Preservation Solution Is Associated With Primary Graft Dysfunction.

BACKGROUND: Although primary graft dysfunction (PGD) is a leading cause of mortality and morbidity early post-heart transplant, relatively little is known regarding mechanisms involved in PGD development. METHODS AND RESULTS: We examined the relationship between cardiac troponin I (cTnI) concentrations in the preservation solution from 43 heart transplant procedures and the development of PGD. Donor hearts were flushed with cold preservation solution (University of Wisconsin [UW] or Custodiol) and stored in the same solution. cTnI concentrations were measured utilizing the i-STAT System and normalized to left ventricular mass. Recipient medical records were reviewed to determine PGD according to the 2014 ISHLT consensus conference. Nineteen patients developed PGD following cardiac transplantation. For both UW and Custodiol, normalized cTnI levels were significantly increased (P = .031 and .034, respectively) for those cases that developed PGD versus no PGD. cTnI levels correlated with duration of ischemic time in the UW group, but not for the Custodiol group. Donor age and donor cTnI (obtained prior to organ procurement) did not correlate with preservation cTnI levels in either UW or Custodiol. CONCLUSIONS: Increased preservation solution cTnI is associated with the development of PGD suggesting preservation injury may be a dominant mechanism for the development of PGD.

Hemodynamic Predictors of Heart Failure Morbidity and Mortality: Fluid or Flow?

BACKGROUND: Patients with advanced heart failure may continue for prolonged times with persistent hemodynamic abnormalities; intermediate- and long-term outcomes of these patients are unknown. METHODS AND RESULTS: We used ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial data to examine characteristics and outcomes of patients with invasive hemodynamic monitoring during an acute heart failure hospitalization. Patients were stratified by final measurement of cardiac index (CI; L/min/m2) and pulmonary capillary wedge pressure (PCWP; mmHg) before catheter removal. The study groups were CI ≥ 2/PCWP < 20 (n = 74), CI ≥ 2/PCWP ≥ 20 (n = 37), CI < 2/PCWP < 20 (n = 23), and CI < 2/PCWP ≥ 20 (n = 17). Final CI was not associated with the combined risk of death, cardiovascular hospitalization, and transplantation (hazard ratio [HR]1.03, 95% confidence interval 0.96-1.11 per 0.2 L/min/m2 decrease, P = .39), but final PCWP ≥ 20 mmHg was associated with increased risk of these events (HR 2.03, 95% confidence interval 1.31-3.15, P < .01), as was higher final right atrial pressure (HR 1.09, 95% confidence interval 1.06-1.12 per mmHg increase, P < .01). CONCLUSION: Final PCWP and final right atrial pressure were stronger predictors of postdischarge outcomes than CI in patients with advanced heart failure. The ability to lower filling pressures appears to be more prognostically important than improving CI in the management of patients with advanced heart failure. ClinicalTrials.govIdentifier: NCT00000619.

A team-based approach to patients in cardiogenic shock.

Cardiogenic shock is a common clinical condition with high in-hospital mortality. Early application of appropriate interventions for cardiogenic shock-including medical therapies, revascularization, temporary hemodynamic support devices, and durable mechanical circulatory support-may improve outcomes. The number and complexity of therapies for cardiogenic shock are increasing, making time-dependent decision-making more challenging. A multidisciplinary cardiogenic shock team is recommended to guide the rapid and efficient use of these available treatments. © 2015 Wiley Periodicals, Inc.