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Sarah Chuzi,1 Fabio Tavora,2 Marcelo Cruz,3 Ricardo Costa,3 Young Kwang Chae,3 Benedito A Carneiro,3 Francis J Giles3 1Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; 2Argos Laboratory, Messejana Heart and Lung Hospital, Fortaleza, Brazil; 3Developmental Therapeutics Program, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA Abstract: Immune checkpoint inhibitors, including cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death-1 (PD-1) inhibitors, represent an effective treatment modality for multiple malignancies. Despite the exciting clinical benefits, checkpoint inhibition is associated with a series of immune-related adverse events (irAEs), many of which can be life-threatening and result in significant treatment delays. Pneumonitis is an adverse event of special interest as it led to treatment-related deaths in early clinical trials. This review summarizes the incidence of pneumonitis during treatment with the different checkpoint inhibitors and discusses the prognostic significance of tumor type. The wide range of clinical, radiographic, and histologic characteristics of checkpoint inhibitor-related pneumonitis is reviewed and followed by guidance on the different management strategies. Keywords: immune checkpoint inhibitors, pneumonitis, anti-PD-1, anti-CTLA-4, immune-related adverse event

Abstract Background Relapse of major depressive disorder (MDD) is a common clinical problem. This study was designed to determine whether residual sleep disturbance (insomnia and hypersomnia) predict risk of relapse during the continuation and maintenance treatment of MDD. Methods A total of 570 patients with MDD were treated with open-label, flexible dose fluoxetine (range 20 to 60 mg; mean dose = 45.8 mg/day; SD = 15.1) for 12 weeks. Under double blind conditions, 262 patients who achieved clinical response were randomly assigned to continue fluoxetine or to switch to placebo for 52 weeks or until relapse. Residual sleep disturbance during the baseline visit of the double-blind phase was assessed using items 4, 5, 6 (insomnia) and 22, 23, 24 (hypersomnia) of the Hamilton Depression Rating Scale (HDRS). Survival analysis was utilized to determine the effect of residual sleep disturbance on risk of relapse. Results The severities of early (P > 0.05), middle (P > 0.05), late (P > 0.05), or total (P > 0.05) residual insomnia were not found to significantly predict risk of relapse during continuation and maintenance-phase treatment. Similarly, the severities of early bedtime (P > 0.05), oversleeping (P > 0.05), napping (P > 0.05), or total (P > 0.05) residual hypersomnia were not found to significantly predict risk of relapse during continuation and maintenance-phase treatment. Conclusion The present study did not identify the severity of residual sleep disturbance among fluoxetine responders to predict risk of MDD relapse. The size of our sample may have precluded us from identifying more modest effects of residual sleep disturbance on the risk of relapse in MDD patients. Future studies are needed to further explore the relationship between residual sleep disturbance and relapse in MDD. Trial Registration ClinicalTrials.gov Identifier: NCT00427128

Background: In October 2018, the US heart transplant (HT) allocation system was revised giving patients with left ventricular assist device (LVAD) intermediate priority status. Few studies have examined the impact of this policy change on outcomes among patients with LVAD. We sought to determine how the allocation change impacted waitlist and posttransplant mortality in patients with LVAD., Methods: We retrospectively assessed the United Network for Organ Sharing registry for patients with LVAD who were listed for or underwent HT between October 2016 and October 2021. We evaluated waitlist mortality using competing risks analysis and a multivariable Fine-Gray model, and posttransplant mortality using Kaplan-Meier survival analysis and a multivariate proportional hazards model., Results: We analyzed data from 3835 patients with LVAD listed for HT and 3486 patients with LVAD who underwent HT during the study period. Listing for HT preallocation change was significantly associated with an increased risk of waitlist mortality (Gray P =0.0058) compared with postallocation change. After adjustment for covariates, mortality differences by listing era were attenuated, but LVAD brand was significantly associated with waitlist mortality (HM3 versus HMII; hazard ratio, 0.38 [95% CI, 0.21-0.69]; P =0.002; HVAD versus HMII; hazard ratio, 0.79 [95% CI, 0.48-1.30]; P =0.36; overall P =0.004). In contrast, HT postallocation change was associated with increased posttransplant mortality (log-rank P =0.0172) compared with preallocation change. In a multivariable analysis, the association with posttransplant mortality between transplant eras was attenuated, but ischemic time (hazard ratio, 1.16 [95% CI, 1.07-1.26]; P <0.001) and status at time of HT (Status 1-3 versus 4; hazard ratio, 1.29 [95% CI, 1.04-1.61]; P =0.02) were significantly associated with posttransplant mortality., Conclusions: Among patients with LVAD, lower waitlist mortality postallocation change was likely driven by improved LVAD technology. Higher posttransplant mortality following the allocation change was largely attributable to longer ischemic times and patient acuity., Competing Interests: Dr Pham serves as a consultant for Abbott, Abiomed, and Medtronic. Dr Wilcox serves as a consultant for Amgen and Abbott and is on the advisory board of Cytokinetics. The other authors report no conflicts.

Competing Interests: Disclosures None.

Heart failure (HF) is characterized by significant symptoms, compromised quality of life, frequent hospital admissions, and high mortality; palliative care (PC) is therefore highly relevant for patients with HF and their clinicians. Multiple guidelines and consensus statements recommend the provision of PC alongside HF management. However, few resources exist to guide the integration of PC into HF care, both for primary PC (provided by HF clinicians in the course of HF care) and specialty PC (provided by PC specialists). Through this consensus statement, the Heart Failure Society of America aims to provide a contemporary, practical guide for clinicians and institutions for how PC should be operationalized in the context of comprehensive HF care. Key components of high-quality, integrated HF-PC are described, with a focus on clinical and operational considerations for providing primary and specialty PC, quality measurement and value demonstration, reimbursement and incentive concerns, and the provision of hospice care., Competing Interests: Declaration of competing interest Dr. Allen receives grant funding from NIH and PCORI; consultant fees from ACI Clinical, Boston Scientific, Cytokinetics, Novartis, Quidel, and UpToDate Dr. Kirkpatrick receives grant funding from NIH Dr. Feder receives grant funding from NIH Dr. Goldstein receives grant funding from NIH; consultant fees from Agilon health Dr. Groninger receives grant funding from NIH Dr. Lewis has received grant funding from the American Heart Association and the National Heart Lung and Blood Institute, and personal fees from Merck, Dal-Cor, Astra Zeneca, and Intellia. The remainder of the authors report no disclosures, (Copyright © 2024. Published by Elsevier Inc.)

Patients and clinicians in the cardiac intensive care unit (CICU) are often tasked with making high-stakes decisions about aggressive or life- sustaining therapies. Shared decision-making (SDM), a collaborative process where patients and clinicians work together to make medical decisions that are aligned with a patient's goals and values, is therefore highly relevant in the CICU, especially in the context of palliative or end-of-life decisions. Despite its importance, there are barriers to optimal integration and implementation of SDM. This review describes the fundamentals and models of SDM, the role of SDM in the CICU, and evidence-based strategies to promote SDM in the CICU., Competing Interests: Disclosure: SG is on the US Cardiology Review editorial board; this did not influence peer review. All other authors have no conflicts of interest to declare., (Copyright © The Author(s), 2024. Published by Radcliffe Group Ltd.)

It is unknown whether racial disparities in access to heart transplantation (HT) are amplified when coupled with substance use. We examined patients evaluated for HT over 8 years at an urban transplant center. We evaluated substance use and race/ethnicity as independent and interactive predictors of HT and left ventricular assist device (LVAD) implantation. Of 1,148 patients evaluated for HT, substance use was cited as an ineligibility factor in 151 (13%) patients, 16 (11%) of whom ultimately received HT. Significantly more non-Hispanic Black (NHB) patients were deemed ineligible due to substance use (n = 59, 19%) compared to other races/ethnicities (non-Hispanic white: n = 68, 12%; other race/ethnicity: n = 24, p = 0.002). No racial differences were observed in the likelihood of HT among patients initially excluded for substances, but more NHB patients ultimately received LVAD than the other racial groups. This study encourages greater awareness of the role of substance use and race in the HT evaluation., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Heart failure (HF) is characterized by significant symptoms, compromised quality of life, frequent hospital admissions, and high mortality, and is therefore well suited to palliative care (PC) intervention. This review elaborates the current PC needs of patients with HF across the spectrum of disease, including patients who undergo advanced HF surgical therapies, and reviews the current data and future directions for PC integration in HF care., Recent Findings: Patients with chronic HF, as well as those who are being evaluated for or who have undergone advanced HF surgical therapies such as left ventricular assist device or heart transplantation, have a number of PC needs, including decision-making, symptoms and quality of life, caregiver support, and end-of-life care. Available data primarily supports the use of PC interventions in chronic HF to improve quality of life and symptoms. PC skills and teams may also help address preparedness planning, adverse events, and psychosocial barriers in patients who have had HF surgeries, but more data are needed to determine association with outcomes., Summary: Patients with HF have tremendous PC needs across the spectrum of disease. Despite this, more data are needed to determine the optimal timing and structure of PC interventions in patients with chronic HF, left ventricular assist device, and heart transplantation. Future steps must be taken in clinical, research, and policy domains in order to optimize care., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Palliative care (PC) is an essential component of high-quality care for people with cardiovascular disease (CVD). However, little is known about the current state of PC education in CVD training, including attitudes toward integration of PC into training and implementation of PC by the program's leadership., Methods: We developed a nationwide, cross-sectional survey that queried education approaches, perspectives and barriers to PC education in general CVD fellowship training. The survey was distributed to 392 members of the American College of Cardiology Program Director (PD) listserv, representing 290 general CVD fellowships between 1/2023 and 4/2023. We performed descriptive and ꭕ 2 analyses of survey data., Results: Of the program's representatives, 56 completed the survey (response rate = 19.3%). Respondents identified themselves as current PDs (89%), associate PDs (8.9%) or former PDs (1.8%), representing a diverse range of program sizes and types and regions of the country. Respondents reported the use of informal bedside teaching (88%), formal didactics (59%), online or self-paced modules (13%), in-person simulation (11%), and clinical rotations (16%) to teach PC content. Most programs covered PC topics at least annually, although there was variability by topic. We found no associations between program demographics and type or frequency of PC education. Most respondents reported dissatisfaction with the quantity (62%) or quality (59%) of the PC education provided. Barriers to PC education included an overabundance of other content to cover (36%) and perceived lack of fellow (20%) or faculty (18%) interest. Comments demonstrated the importance of PC education in fellowship, the lack of a requirement to provide PC education, difficulty in covering all topics, and suggestions of how PC skills should be taught., Conclusions: In a national survey of CVD educational leadership concerning approaches to PC education in CVD training, respondents highlighted both challenges to implementation of formal PC curricula in cardiology training and opportunities for comprehensive PC education., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Clinical trials in heart transplantation (HT) recipients have largely focused on objective outcomes such as survival; however, there is a paucity of data regarding the use of patient-reported outcome measures (PROMs) in these studies. We aimed to characterize the use of PROMs in registered clinical studies of HT recipients., Methods: All clinical studies of adult HT recipients were queried from ClinicalTrials.gov and stratified by inclusion of PROMs. Studies reporting PROMs were identified via specific search terms using the "outcomes measures" field. Summary statistics compared characteristics of studies with and without PROMs., Results: Between November 1999 and August 2022, 227 studies of HT recipients were registered on ClinicalTrials.gov. PROMs were included in 11% ( n = 24/227) of studies. Studies reporting PROMs were more likely to be conducted outside of the United States (91.7% vs 54.2%, p < 0.001) and report a greater number of primary/secondary outcomes (PROMs: median 7 [interquartile ranges (IQR): 4, 9] vs no PROMs: median 3 [IQR: 2, 6]; p < 0.001). The majority of studies reporting PROMs (58.3%) were initiated after 2020. Twenty-one distinct PROM tools/domains were reported as outcome measures, with the Short Form Health Survey 36 being most frequently used ( n = 10/24). Thirteen of the 21 PROMs included questions assessing mental health, whereas only 3 PROM tools were cardiac-specific., Conclusions: About 1 in 10 registered clinical trials of HT recipients includes PROMs, and mental health is the most commonly assessed PROM domain. Development and validation of PROM tools is needed to fully assess health-related quality of life in HT recipients.

Competing Interests: Disclosures None.

Background: End-stage liver disease (ESLD) and heart failure (HF) often coexist and are associated with significant morbidity and mortality. However, the true incidence of HF among patients with ESLD remains understudied., Objective: This study aims to evaluate the association between ESLD and incident HF in a real-world clinical cohort., Design and Participants: A retrospective electronic health records database analysis of individuals with ESLD and frequency-matched controls without ESLD in a large integrated health system., Main Measures: The primary outcome was incident HF, which was defined by the International Classification of Disease codes and manually adjudicated by physician reviewers. The Kaplan-Meier method was used to estimate the cumulative incidence of HF. Multivariate proportional hazards models adjusted for shared metabolic factors (diabetes, hypertension, chronic kidney disease, coronary heart disease, body mass index) were used to compare the risk of HF in patients with and without ESLD., Key Results: Of 5004 patients (2502 with ESLD and 2502 without ESLD), the median (Q1-Q3) age was 57.0 (55.0-65.0) years, 59% were male, and 18% had diabetes. Over a median (Q1-Q3) follow-up of 2.3 (0.6-6.0) years, 121 incident HF cases occurred. Risk for incident HF was significantly higher for patients with ESLD compared with the non-ESLD group (adjusted HR: 4.67; 95% CI: 2.82-7.75; p < 0.001), with the majority of the ESLD group (70.7%) having HF with preserved ejection fraction (ejection fraction ≥ 50%)., Conclusion: ESLD was significantly associated with a higher risk of incident HF, independent of shared metabolic risk factors, with the predominant phenotype being HF with preserved ejection fraction., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background: Information about health-related quality of life (HRQOL) among caregivers of older patients with heart failure who receive heart transplantation (HT) and mechanical circulatory support (MCS) is sparse. We describe differences and factors associated with change in HRQOL before and early post-surgery among caregivers of older heart failure patients who underwent 3 surgical therapies: HT with pretransplant MCS (HT MCS), HT without pretransplant MCS (HT non-MCS), and long-term MCS., Methods: Caregivers of older patients (60-80 years) from 13 US sites completed the EQ-5D-3 L visual analog scale (0 [worst]-100 [best] imaginable health state) and dimensions before and 3 and 6 months post-surgery. Analyses included linear regression, t tests, and nonparametric tests., Results: Among 227 caregivers (HT MCS=54, HT non-MCS=76, long-term MCS=97; median age 62.7 years, 30% male, 84% White, 83% spouse/partner), EQ-5D visual analog scale scores were high before (84.8±14.1) and at 3 (84.7±13.0) and 6 (83.9±14.7) months post-surgery, without significant differences among groups or changes over time. Patient pulmonary hypertension presurgery (β=-13.72 [95% CI, -21.07 to -6.36]; P <0.001) and arrhythmia from 3 to 6 months post-operatively (β=-14.22 [95% CI, -27.41 to -1.02]; P =0.035) were associated with the largest decrements in caregiver HRQOL; patient marital/partner status (β=6.21 [95% CI, 1.34-11.08]; P =0.013) and presurgery coronary disease (β=8.98 [95% CI, 4.07-13.89]; P <0.001) were associated with the largest improvements., Conclusions: Caregivers of older patients undergoing heart failure surgeries reported overall high HRQOL before and early post-surgery. Understanding factors associated with caregiver HRQOL may inform decision-making and support needs., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02568930., Competing Interests: Disclosures Dr Jane received grant support from the American Heart Association and the National Institutes of Health; is a consultant for Amgen, Abbott, Abiomed, and Novartis; and is on the advisory board of Abiomed and Cytokinetics. Dr Kao participated in the advisory board for CareDx and Bioventrix. Dr Spertus is a consultant at Amgen, Novartis, Bayer, Myokardia, and Janssen; on the scientific advisory board of United HealthCare; on the board of directors of BlueCross BlueShield, Kansas City; and is the copyright holder to the Kansas City Cardiomyopathy Questionnaire. Dr Yancy received spousal employment from Abbott Labs Inc. Dr Petty received speaking honorarium from Abbott Inc. M. Murray is a consultant on a research project at GE Healthcare. Dr Silvestry is a consultant at Abiomed, Medtronic, Syncardia, and Abbott. Dr Kirklin is a director of the DCC for STS INTERMACS; and received grant support from the National Institutes of Health/National Institute on Aging. Dr Grady is a consultant at Amgen Inc; is a paid lecturer for the American Heart Association; and received grant support from the National Institutes of Health (National Institute on Aging and National Heart, Lung, and Blood Institute).

Background Accountable care organizations (ACOs) aim to improve health care quality and reduce costs, including among patients with heart failure (HF). However, variation across ACOs in admission rates for patients with HF and associated factors are not well described. Methods and Results We identified Medicare fee-for-service beneficiaries with HF who were assigned to a Medicare Shared Savings Program ACO in 2017 and survived ≥30 days into 2018. We calculated risk-standardized acute admission rates across ACOs, assigned ACOs to 1 of 3 performance categories, and examined associations between ACO characteristics and performance categories. Among 1 232 222 beneficiaries with HF, 283 795 (mean age, 81 years; 54% women; 86% White; 78% urban) were assigned to 1 of 467 Medicare Shared Savings Program ACOs. Across ACOs, the median risk-standardized acute admission rate was 87 admissions per 100 people, ranging from 61 (minimum) to 109 (maximum) admissions per 100 beneficiaries. Compared to the overall average, 13% of ACOs performed better on risk-standardized acute admission rates, 72% were no different, and 14% performed worse. Most ACOs with better performance had fewer Black beneficiaries and were not hospital affiliated. Most ACOs that performed worse than average were large, located in the Northeast, had a hospital affiliation, and had a lower proportion of primary care providers. Conclusions Admissions are common among beneficiaries with HF in ACOs, and there is variation in risk-standardized acute admission rates across ACOs. ACO performance was associated with certain ACO characteristics. Future studies should attempt to elucidate the relationship between ACO structure and characteristics and admission risk.

Background: Multiple guidelines recommend specialty palliative care (PC) for patients with heart failure (HF), including patients with left ventricular assist devices (LVADs). However, the degree of integration and clinicians' perceptions of PC in HF care remain incompletely characterized., Methods and Results: A 36-item survey was sent to 2109 members of the Heart Failure Society of America. Eighty respondents (53% physicians), including 51 respondents from at least 42 medical centers, completed the survey, with the majority practicing in urban (76%) academic medical centers (62%) that implanted LVADs (81%). Among the 42 unique medical centers identified, respondents reported both independent (40%) and integrated (40%) outpatient PC clinic models, whereas 12% reported not having outpatient PC at their institutions. A minority (12%) reported that their institution used triggered PC referrals based on objective clinical data. Of respondents from LVAD sites, the majority reported that a clinician from the PC team was required to see all patients prior to implantation, but there was variability in practices. Among all respondents, the most common reasons for PC referral in HF were poor prognosis, consideration of advanced cardiac therapies or other high-risk procedures and advance-care planning or goals-of-care discussions. The most frequent perceived barriers to PC consultation included lack of PC clinicians, unpredictable HF clinical trajectories and limited understanding of how PC can complement traditional HF care., Conclusion: PC integration and clinician perceptions of services vary in HF care. More research and guidance regarding evidence-based models of PC delivery in HF are needed., (Published by Elsevier Inc.)

Objectives: This study aims to examine a novel patient-centered metric of time spent engaging in left ventricular assist device (LVAD)-related clinical care outside the home., Background: Although LVAD implantation can improve survival and functional capacity in patients with advanced heart failure, this may occur at the expense of significant time spent engaging in LVAD-related health care activities., Methods: The authors retrospectively assessed consecutive patients at a single center who received a continuous-flow LVAD between May 9, 2008, and December 31, 2019, and queried health care encounters after implantation, including all inpatient encounters and LVAD-related ambulatory encounters. Patient-level time metrics were determined, including the total number of days with any health care encounter, and the total estimated time spent receiving care. The primary outcome was the proportion (%) of days alive with an LVAD spent engaged in at least 1 health care encounter. The secondary outcome was the proportion (%) of total time alive with an LVAD spent receiving care., Results: Among 373 patients, the median number of days alive with LVAD was 390 (IQR: 158-840 days). Patients had a median number of 88 (IQR: 45-161) days with ≥1 health care encounter, accounting for 23.2% (IQR: 16.3%-32.4%) of their days alive with an LVAD. A median 6.0% (IQR: 2.1%-14.1%) and 15.0% (IQR: 10.7%-20.0%) of total days alive were spent in inpatient and ambulatory encounters, respectively. Patients spent a median of 592 (IQR: 197-1,257) hours receiving care, accounting for 5.6% (IQR: 2.2%-12.7%) of their total time alive with an LVAD., Conclusions: LVAD patients spent more than 1 of every 5 days engaging in health care. Our findings may inform strategies to improve efficiency of postdischarge care delivery and expectations for post-treatment care., Competing Interests: Funding Support and Author Disclosures Research reported in this publication was supported, in part, by Northwestern University Clinical and Translational Sciences Institute’s Enterprise Data Warehouse. Dr Ahmad has received consulting fees from Amgen, Teladoc Linvongo, and Pfizer unrelated to this manuscript. Dr Allen has received grant funding from the AHA, NIH, and PCORI; and has received consultative fees from Abbott, ACI Clinical, Boston Scientific, Cytokinetics, and Novartis. Dr Grady has received consulting fees from Amgen, and has received grant funding from the NHLBI and NIH. Dr Rich has received consulting fees from Abbott. Dr Pham serves as a consultant for MedTronic, Abbott, and Abiomed. Dr Wilcox has received grant funding from the AHA and NIH; has received consulting fees from Amgen, Abbott, Abiomed, and Novartis; and serves on the scientific advisory boards for Abiomed and Cytokinetics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background Patients with left ventricular assist devices (LVADs) implanted as destination therapy may receive suboptimal preparation for and care at the end of life, but there is limited understanding of the reasons for these shortcomings. Exploring perceptions of individuals (caregivers and clinicians) who are closely involved in the end-of-life experience with patients with destination therapy LVADs can help identify key opportunities for improving care. Methods and Results We conducted semistructured qualitative interviews with 7 bereaved caregivers of patients with destination therapy LVADs and 10 interdisciplinary LVAD clinicians. Interviews explored perceptions of preparing for end of life, communicating about end of life, and providing and receiving end-of-life care, and were analyzed using a 2-step team-based inductive approach to coding and analysis. Six themes pertaining to end-of-life experiences were derived: (1) timing end-of-life discussions in the setting of unpredictable illness trajectories, (2) prioritizing end-of-life preparation and decision-making, (3) communicating uncertainty while providing support and hope, (4) lack of consensus on responsibility for end-of-life discussions, (5) perception of the LVAD team as invincible, and (6) divergent perceptions of LVAD withdrawal. Conclusions This study revealed 6 unique aspects of end-of-life care for patients with destination therapy LVADs as reported by clinicians and caregivers. Themes coalesced around communication, team-based care, and challenges unique to patients with LVADs at end of life. Programmatic changes may address some aspects, including training clinicians in LVAD-specific communication skills. Other aspects, such as standardizing the role of the palliative care team and developing practical interventions that enable timely advance care planning during LVAD care, will require multifaceted interventions.

Place of death is a key indicator of quality of end-of-life care, and most people with a terminal diagnosis prefer to die at home. Home has surpassed the hospital as the most common location of all-cause and total cancer-related deaths in the United States. However, trends in place of death due to hepatocellular carcinoma (HCC), which is uniquely comanaged by hepatologists and oncologists, have not been described. We analysed US death certificate data from 2003 to 2018 for the proportion of deaths over time at medical facilities, nursing facilities, hospice facilities and home, for HCC and non-HCC cancer. The proportion of deaths increased from 0.6% to 15.2% in hospice facilities (P trend < 0.0001) but did not change at home. In multivariable analysis, persons with HCC were more likely than persons with non-HCC cancer to die in medical facilities, while persons with HCC were less likely to die at home., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Left ventricular longitudinal strain (LVLS) performed using subcostal windows is a novel alternative for patients who require strain imaging but have poor apical windows. We investigated the reproducibility and inter-vendor variability of subcostal LVLS. One hundred and twenty-four echocardiographic studies were analysed from 73 women with early stage HER2-positive breast cancer. Speckle tracking strain was performed offline using EchoPAC and TomTec on subcostal 4-chamber and 3-chamber views to obtain subcostal 4-chamber (SC4&#95;LS) and 3-chamber (SC3&#95;LS) LVLS which was then averaged (SCav&#95;LS). Reproducibility of subcostal single chamber and averaged LVLS were assessed. Measurements between platforms were compared. Strain was reported in absolute magnitude. EchoPAC measurements of SC3&#95;LS (20.5 ± 2.4% vs. 21.2 ± 2.5%, p = 0.002) and SCav&#95;LS (20.9 ± 2.1% vs. 21.2 ± 2.1%, p = 0.02) were lower than TomTec measurements while SC4&#95;LS was similar (21.3 ± 2.7% vs. 21.3 ± 2.5%, p = 0.94). Mean differences between EchoPAC and TomTec were ≤ 0.6% strain units for all subcostal LVLS measurements; SCav&#95;LS showed the narrowest limits of agreement (LOA) (mean difference - 0.3%, LOA - 3.2 to 2.6%). EchoPAC and TomTec measurements of SCav&#95;LS showed good correlation (r = 0.76, p < 0.001). Intra-observer and inter-observer analysis showed good reproducibility. Inter-observer variability was lower than inter-vendor variability; SCav&#95;LS was most reproducible: inter-observer relative mean error was 3.6% for EchoPAC and 4.3% for TomTec and inter-observer LOA were ± 2.1% for EchoPAC and ± 2.6% for TomTec. Averaged subcostal LVLS was highly reproducible with inter-observer variability comparable to GLS. Inter-vendor differences in averaged subcostal LVLS were small but statistically significant.

Competing Interests: Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

The US Food and Drug Administration issued a black box warning in 2012 regarding the association of statin use with cognitive impairment. This may deter patients and practitioners from using statins for guideline-directed indications. Large studies have not shown an increase in cognitive impairment with statin use. MEDLINE, EMBASE, and Cochrane databases were searched up to October 2019. We present an up-to-date systematic review of randomized controlled trials (RCTs) and prospective observational studies examining the association between statin use and cognitive status in a population aged ≥60 years. Twenty-four studies with 1,404,459 participants were included in the review. Twenty-one were prospective observational studies, and 3 were RCTs. All 3 RCTs, which ranged from 3.2 to 5.6 years of follow-up, showed no significant association between statin use and adverse cognitive effects (odds ratio [OR] 1.03 [0.82-1.30]) and (OR 1.0 [0.61-1.65]). The mean difference in the Mini-Mental State Examination was insignificant (0.06 [-0.04 to 0.16]) in the third RCT. The follow-up for observational studies ranged from 3 to 15 years. Ten observational studies showed reduced incidence of dementia. Seven showed no association with incident dementia. Three studies showed decline in cognition was similar, whereas one showed slower decline with statin use. There was no evidence of adverse cognitive effects, including incidence of dementia, deterioration in global cognition, or specific cognitive domains associated with statin use in individuals aged ≥60 years. Future studies should examine this association in studies with longer follow-up periods., (Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: The location of death is an important component of end-of-life care. However, contemporary trends in the location of death for cardiovascular deaths related to heart failure (CV-HF) and comparison to cancer deaths have not been fully examined., Methods: We analyzed data from the Centers for Disease Control and Prevention's Control Wide-Ranging Online Data for Epidemiologic Research database between 2003 and 2017 to identify location of death for CV-HF and cancer deaths. The proportions of deaths that occurred in a hospice facility, home, and medical facility were tested for trends using linear regression. Odds ratios were calculated to determine the odds of death occurring in a hospice facility or home (versus a medical facility) stratified by sex and race., Results: We identified 2 940 920 CV-HF and 8 852 066 cancer deaths. Increases were noted in the proportion of CV-HF deaths in hospice facilities (0.2% to 8.2%; P trend <0.001) and at home (20.6% to 30.7%; P trend <0.001), whereas decreases were noted in the proportion of deaths in medical facilities (44.5% to 31.0%; P trend <0.001) and nursing homes (30.8% to 25.7%; P trend <0.001). The odds of dying in a hospice facility (odds ratio, 1.79 [1.75-1.82]) or at home (odds ratio, 1.55 [1.53-1.56]) versus a medical facility was higher for whites versus blacks. The rate of increase in proportion of deaths in hospice facilities was higher for cancer deaths (β=1.05 [95% CI, 0.97-1.12]) than for CV-HF deaths (β=0.61 [95% CI, 0.58-0.64])., Conclusions: The proportion of CV-HF deaths occurring in hospice facilities is increasing but remains low. Disparities are noted whereby whites are more likely to die in hospice facilities or at home versus medical facilities compared with blacks. More research is needed to determine end-of-life preferences for patients with HF and identify the basis for these differences in location of death.

Purpose of Review: Patients with heart failure (HF) have an increased symptom burden and complex psychosocial and decision-making needs that necessitate the integration of palliative care. However, in the current era, palliative care is frequently evoked for these patients only at the end-of-life or in the inpatient setting; rarely is palliative care proactively utilized in outpatients with HF. The purpose of this review is to evaluate the current state of palliative care and heart failure and to provide a roadmap for the integration of palliative care into outpatient HF care., Recent Findings: Recent studies, including PAL-HF, CASA, and SWAP-HF, have demonstrated that structured palliative care interventions may improve quality of life, depression, anxiety, understanding of prognosis, and well-being in HF. HF is associated with high mortality risk, significant symptom burden, and impaired quality of life. Palliative care can meet many of these needs; however, in the current era, palliative care consultations in HF occur late in the disease course and too often in the inpatient setting. Primary palliative care should be provided to all outpatients with heart failure based on their needs, with referral to secondary palliative care provided based on certain triggers and milestones.

Context: Early integration of palliative care (PC) into adult oncology practice has been shown to improve quality of life and health care utilization; however, little is known about PC in young adults with cancer. Objectives: Our primary objective was to determine rates and timing of PC consultation in young adult patients with advanced solid tumor cancer at a single institution. Methods: We conducted a retrospective analysis of young adults of age 18-39 years with advanced solid tumor malignancy at an urban academic medical center between June 1, 2014 and June 30, 2015. Results: Of 129 patients identified, 70 of 129 (54%) had a PC consult and 34 of 70 were inpatient-only consults. PC consults occurred for a median of 104 days before death, and for those with inpatient-only consults, PC consults occurred for a median of 18 days. Patients with worse recent Eastern Cooperative Oncology Group (ECOG) performance status were more likely to have had a PC consult ( p  < 0.001). Of the patients who died during the study period, patients with PC consults were more likely to have been hospitalized (72% vs. 47%), in the intensive care unit (21% vs. 0%), in the emergency room (ER) (72% vs. 47%), and have received chemotherapy (17% vs. 0%) within 30 days of death compared with those who did not have a consult; however, these differences were not statistically significant. Conclusion: In this analysis, over half of young adults with advanced solid tumors received PC consults. PC consult typically occurred for one year after diagnosis and about three months before death. Additional research is needed to identify how to better integrate PC early in this patient population and assess the resulting impact.

Importance: The number of patients living with end-stage heart failure is steadily growing, and ambulatory intravenous inotropic support is increasingly offered as a palliative therapy. However, the optimal ways to initiate, manage, and discuss the risks and benefits of palliative inotropes in the current era of heart failure care are unclear., Observations: The initiation of palliative inotropes requires an understanding of clinical, psychosocial, and economic factors, as well as the changing risk-to-benefit calculus. While earlier studies suggested that outpatient inotrope therapy provided symptomatic benefit at the expense of reduced survival, recent data suggest that the survival of patients receiving chronic inotropes may be improving over time, perhaps owing to the use of implantable cardioverter defibrillators, concurrent guideline-directed medical therapy, or lower doses of inotropes. The use of heart failure therapies, such as β-blockade, among patients receiving palliative inotropes is controversial but may be appropriate in select situations., Conclusions and Relevance: The role of palliative inotropes is changing in tandem with advances in chronic heart failure care. However, there remains a profound lack of data and guidance on the effect of palliative inotropes on quality of life and mortality and little consensus on how this therapy can be optimally used in contemporary practice. This review provides a framework for the prescription and management of palliative inotropes, including a discussion of potential risks and benefits and a roadmap for how to initiate, maintain, and wean them.

These 4 hypothetical cases highlight some of the new features in the 2018 American Heart Association/American College of Cardiology multisociety cholesterol management guidelines. Topics include management issues in a secondary prevention patient judged to be at very high risk of another event, a patient with familial hypercholesterolemia with a low-density lipoprotein cholesterol level of 190 mg/dL or greater (to convert to millimoles per liter, multiply by 0.0259), a primary prevention patient with intermediate (7.5%-19.9%) 10-year atherosclerotic cardiovascular risk, and a patient who has statin-associated adverse effects. A multiple-choice format is used to engage clinicians in selecting the best choice based on guidance from the new 2018 cholesterol management guidelines.

Background: Strain imaging is a robust clinical tool in cardiac surveillance of patients with breast cancer. However, image quality and therefore ability to accurately measure strain are often limited in this patient group because of tissue expanders, implants, and/or flap reconstruction. The aim of the present study was to evaluate the feasibility of measuring left ventricular longitudinal strain (LVLS) in the echocardiographic subcostal view in female patients with breast cancer., Methods: A total of 110 studies from 68 female patients with breast cancer were included. The feasibility of LVLS speckle-tracking measurements in the apical three-chamber (3C) and four-chamber (4C) views and in the subcostal 3C and 4C views was evaluated. The LVLS speckle-tracking measurements obtained in these two echocardiographic views were compared using intraclass correlation coefficients and Bland-Altman analyses., Results: The feasibility of LVLS in the apical 3C and 4C views was 98.1% and 98.1%, respectively. In comparison, the feasibility of LVLS in the subcostal 3C and 4C views was 93.6% and 96.3%, respectively. A high degree of reliability was found between apical and subcostal LVLS 3C and 4C measurements. For the 3C view, the average measure intraclass correlation coefficient was 0.81 (95% CI, 0.72-0.88). For the 4C view, the average measure intraclass correlation coefficient was 0.80 (95% CI, 0.70-0.87). Bland-Altman analysis showed good agreement between apical and subcostal measurements in both the 3C and 4C views., Conclusions: Subcostal 3C and 4C LVLS can be reliably measured, with good agreement with conventional LVLS from the apical views, in female patients with breast cancer. Importantly, the subcostal view may provide a novel alternative for trending LVLS in patients with breast cancer who have technically limited apical windows., (Copyright © 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Introduction: In 2013, the Centers for Medicare and Medicaid Services issued a mandate requiring that all patients undergoing destination therapy ventricular assist device (DT VAD) implantation have access to a palliative care team before surgery. Subsequently, many VAD programs implemented a mandatory preimplantation palliative care consultation for patients considering DT VAD. However, little is known about the quality of these consults., Methods: All patients undergoing DT VAD implantation at Northwestern Memorial Hospital from October 30, 2013 (the Centers for Medicare and Medicaid Services decision date), through March 1, 2018, were included. Palliative care consultation notes were qualitatively analyzed for elements of "palliative care assessment" and preparedness planning., Results: Sixty-eight preimplantation palliative care consultations were analyzed. Fifty-six percent of the consults occurred in the intensive care unit, and the median time from consult to VAD implant was six days. General palliative care elements were infrequently discussed. Furthermore, the elements of preparedness planning-device failure, post-VAD health-related quality of life, device complications, and progressive comorbidities-were discussed in only 10%, 54%, 49%, and 12% of consultations, respectively., Conclusions: One-time preimplantation palliative care consultations at our institution do not lead to completion of preparedness planning or even general palliative care assessment. Further work is needed to determine the most effective way to integrate palliative care into preimplantation care., (Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Inpatient telemetry monitoring is a commonly used technology designed to detect and monitor life-threatening arrhythmias. However, residents are rarely educated in the proper use and interpretation of telemetry monitoring., Methods: We developed a training module containing an educational video, PowerPoint presentation, and hands-on interactive learning session with a telemetry expert. The module highlights proper use of telemetry monitoring, recognition of telemetry artifact, and interrogation of telemetry to identify clinically significant arrhythmias. Learners completed pre- and postcurriculum knowledge-based assessments and a postcurriculum survey on their experience with the module. In total, the educational curriculum had three 60-minute sessions., Results: Thirty-two residents participated in the training module. Residents scored higher on the posttest (77% ± 12%) than on the pretest (70% ± 12%), t (31) = -4.3, p < .001. Wilcoxon signed rank tests indicated PGY-3s performed better on the posttest ( Mdn = 0.86) than on the pretest ( Mdn = 0.72), z = -2.19, p = .031. PGY-2s also performed better on the posttest ( Mdn = 0.86) than on the pretest ( Mdn = 0.76), z = -2.04, p = .042. There was no difference between pretest ( Mdn = 0.66) and posttest ( Mdn = 0.71) scores for PGY-1s, z = -1.50, p = .142. The majority of residents reported that the telemetry curriculum boosted their self-confidence, helped prepare them to analyze telemetry on their patients, and should be a required component of the residency., Discussion: This module represents a new paradigm for teaching residents how to successfully and confidently interpret and use inpatient telemetry., Competing Interests: None to report.

Background: Mastery learning in health professions education requires learners to learn and undergo assessment until they demonstrate a high level of competence. Setting defensible standards is key to accurately assessing educational outcomes in mastery learning. The Mastery Angoff method was proposed recently to set a minimum passing standard (MPS) for mastery learning curricula. However, it is unknown whether prior knowledge of trainee performance affects judges' decisions about setting an MPS using the Mastery Angoff method., Objective: We sought to determine the effect of introducing baseline data about trainee performance on faculty judges' decisions about the Mastery Angoff MPS for a written examination., Methods: We developed a mastery learning curriculum to train internal medicine residents and cardiology fellows about the correct interpretation of inpatient telemetry monitoring. All learners were required to meet or exceed an MPS on a 35-item written examination at the end of training. The MPS was set in 2017 by judges who used the item-based Mastery Angoff method without prior examinee performance information. The judges subsequently reevaluated the test items after receiving baseline data about trainee performance collected during pilot testing. Mastery Angoff MPSs with and without baseline performance data were compared., Results: Twelve judges participated in the standard-setting exercise. The initial MPS was similar to the repeat MPS set after judges received trainee performance data (86.2% versus 86.9%, P  = .23)., Conclusions: Prior knowledge about medical trainee performance data did not affect MPS as determined by the Mastery Angoff procedure., Competing Interests: Conflict of interest: The authors declare they have no competing interests.

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm that is associated with diminished quality of life, thrombohemorrhagic complications, and transformation to myelofibrosis (MF) and acute leukemia (AML). The important recent discoveries of driver mutations, including the calreticulin gene in addition to JAK2 and MPL, have led to a greater understanding of disease pathogenesis and set the stage for the advent of more sophisticated prognostic, diagnostic, and therapeutic strategies. In this paper we summarize recent studies describing the molecular basis of ET. We review the prognostic importance of establishing a 'true' ET diagnosis, as well as risk factors for the development of adverse outcomes including thrombosis, AML (2% risk at 15 years), and MF (9% risk at 15 years). Finally, we discuss the decision to initiate treatment and assess the quality of evidence supporting the use of established, available therapies as well as novel treatments. Special situations, such as pregnancy, familial ET, and extreme thrombocytosis will also be discussed.

Context: Elderly subjects have reduced mitochondrial function. However, it remains unclear whether the decline in mitochondrial function begins earlier in the life span., Objective: The objective of the study was to determine skeletal muscle mitochondrial oxidative phosphorylation by (31)phosphorous-magnetic resonance spectroscopy (MRS) across a variety of age groups., Design: This was a cross-sectional study of 121 healthy normal-weight and overweight individuals from age 8 to 55 yr., Setting: The study was conducted at a single university medical center in Boston, MA., Participants: Participants included 68 children and 53 adults from the Boston community., Interventions and Main Outcome Measures: Phosphocreatine (PCr) recovery was evaluated by (31)phosphorous-MRS after submaximal exercise. Subjects were also evaluated with anthropometric measurements, metabolic profiles, and measures of physical activity., Results: PCr recovery determined by (31)phosphorous-MRS is positively associated with age in univariate analysis in a cohort of individuals aged 8-55 yr (r = +0.55, P < 0.0001). Stratification of subjects into four age groups (prepubertal and early pubertal children, pubertal and postpubertal children < 18 yr, young adults aged 18-39 yr, and middle aged adults aged 40-55 yr) demonstrates prolongation of PCr recovery with increasing age across the four groups (P < 0.0001 by ANOVA). The relationship between PCr recovery and age remains strong when controlling for gender; race; ethnicity; body mass index; measures of physical activity and inactivity; and anthropometric, nutritional, and metabolic parameters (P < 0.004)., Conclusions: Skeletal muscle PCr recovery measured by (31)phosphorous-MRS is prolonged with age, even in children and young adults.

The objective of this study was to assess the relationship between early changes in anxiety/somatization symptoms and treatment outcome among major depressive disorder patients during a 12-week trial of fluoxetine. We also examined the relationship between anxious depression and treatment response. Five hundred and ten major depressive disorder patients received 12 weeks of fluoxetine with flexible dosing [target dosages: 10 mg/day (week 1), 20 mg/day (weeks 2-4), 40 mg/day (weeks 4-8), and 60 mg/day (weeks 5-12)]. We assessed the relationship between early changes in 17-item Hamilton Rating Scale for Depression (HAMD-17)-anxiety/somatization factor items and depressive remission, as well as whether anxious depression at baseline predicted remission at study endpoint. Baseline HAMD-17 scores were considered as covariates and the Bonferroni correction (P < or = 0.008) was used for multiple comparisons. Adjusting for baseline HAMD-17 scores, patients who experienced greater early improvement in somatic symptoms (gastrointestinal) were significantly more likely to attain remission (HAMD-17 <8) at endpoint than those without early improvement (P=0.006). Early changes in the remaining items did not predict remission, nor did anxious depression at baseline. In conclusion, among the anxiety/somatization factor items, only early changes in somatic symptoms (gastrointestinal) predicted remission. Future studies are warranted to further investigate this relationship as well as that between anxious depression and treatment outcome.

Background: Developing the means to identify smokers at high risk for relapse could advance relapse prevention therapy. We hypothesized that functional magnetic resonance imaging (fMRI) reactivity to smoking-related cues, measured before a quit attempt, could identify smokers with heightened relapse vulnerability., Methods: Before quitting smoking, 21 nicotine-dependent women underwent fMRI during which smoking-related and neutral images were shown. These smokers also were tested for possible attentional biases to smoking-related words using a computerized emotional Stroop (ES) task previously found to predict relapse. Smokers then made a quit attempt and were grouped based on outcomes (abstinence vs. slip: smoking > or = 1 cigarette after attaining abstinence). Prequit fMRI and ES measurements in these groups were compared., Results: Slip subjects had heightened fMRI reactivity to smoking-related images in brain regions implicated in emotion, interoceptive awareness, and motor planning and execution. Insula and dorsal anterior cingulate cortex (dACC) reactivity induced by smoking images correlated with an attentional bias to smoking-related words. A discriminant analysis of ES and fMRI data predicted outcomes with 79% accuracy. Additionally, smokers who slipped had decreased fMRI functional connectivity between an insula-containing network and brain regions involved in cognitive control, including the dACC and dorsal lateral prefrontal cortex, possibly reflecting reduced top-down control of cue-induced emotions., Conclusions: These findings suggest that the insula and dACC are important substrates of smoking relapse vulnerability. The data also suggest that relapse-vulnerable smokers can be identified before quit attempts, which could enable personalized treatment, improve tobacco-dependence treatment outcomes, and reduce smoking-related morbidity and mortality., (Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Relapse of major depressive disorder (MDD) is a common clinical problem. Identifying relapse predictors could lead to strategies that reduce relapse risk. This study is designed to determine whether residual symptoms predict relapse risk during the continuation/maintenance treatment of MDD. 570 MDD patients received open-label fluoxetine for 12 weeks. Under double blind conditions, 262 patients who responded by week 12 were randomly assigned to continue fluoxetine or switch to placebo for 52 weeks or until relapse. Residual symptoms were measured using the Symptom Checklist-90 and the Symptom Questionnaire. The relationship between residual symptom severity and relapse risk was assessed. Without adjusting for overall residual symptom severity, a greater severity of residual obsessive-compulsive and phobic anxiety symptoms predicted greater relapse risk. After adjusting for overall residual symptom severity, only severity of phobic anxiety symptoms predicted relapse risk. The predictive value of phobic anxiety symptoms with respect to relapse risk was independent of treatment assignment. The results indicated that there may be a specific pattern of residual symptoms associated with depressive relapse during antidepressant continuation/maintenance, which is unrelated to treatment assignment. Future studies are needed to further explore the relationship between residual symptoms and relapse risk in MDD., Clinical Implications: (1) It is important to treat residual symptoms among antidepressant responders/remitters in order to decrease relapse risk. (2) Clinicians should target residual phobic anxiety symptoms in order to decrease relapse risk. (3) Clinicians should target residual obsessive-compulsive symptoms in order to decrease relapse risk., Limitations: (1) limited generalizability due to inclusion/exclusion criteria; (2) lack of active comparator treatment group; (3) post hoc analysis.

Background: Relapse of major depressive disorder (MDD) is a common clinical problem. This study was designed to determine whether residual sleep disturbance (insomnia and hypersomnia) predict risk of relapse during the continuation and maintenance treatment of MDD., Methods: A total of 570 patients with MDD were treated with open-label, flexible dose fluoxetine (range 20 to 60 mg; mean dose = 45.8 mg/day; SD = 15.1) for 12 weeks. Under double blind conditions, 262 patients who achieved clinical response were randomly assigned to continue fluoxetine or to switch to placebo for 52 weeks or until relapse. Residual sleep disturbance during the baseline visit of the double-blind phase was assessed using items 4, 5, 6 (insomnia) and 22, 23, 24 (hypersomnia) of the Hamilton Depression Rating Scale (HDRS). Survival analysis was utilized to determine the effect of residual sleep disturbance on risk of relapse., Results: The severities of early (P > 0.05), middle (P > 0.05), late (P > 0.05), or total (P > 0.05) residual insomnia were not found to significantly predict risk of relapse during continuation and maintenance-phase treatment. Similarly, the severities of early bedtime (P > 0.05), oversleeping (P > 0.05), napping (P > 0.05), or total (P > 0.05) residual hypersomnia were not found to significantly predict risk of relapse during continuation and maintenance-phase treatment., Conclusion: The present study did not identify the severity of residual sleep disturbance among fluoxetine responders to predict risk of MDD relapse. The size of our sample may have precluded us from identifying more modest effects of residual sleep disturbance on the risk of relapse in MDD patients. Future studies are needed to further explore the relationship between residual sleep disturbance and relapse in MDD., Trial Registration: ClinicalTrials.gov Identifier: NCT00427128.