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Background: It is unclear how metabolic syndrome (MetS) and diabetes affect Gal-3 (galectin 3) levels and the resulting implications for heart failure (HF) risk. We assessed relationships of MetS and diabetes with Gal-3, and their joint associations with incident HF., Methods and Results: We included 8445 participants without HF (mean age, 63 years; 59% men; 16% Black race) at ARIC (Atherosclerosis Risk in Communities) study visit 4 (1996-1999). We categorized participants as having MetS only, MetS with diabetes, or neither, and by quartiles of MetS severity Z score. We assessed cross-sectional associations of metabolic risk categories with high Gal-3 level (≥75th percentile) using logistic regression. We used Cox regression to evaluate combined associations of metabolic risk categories and Gal-3 quartiles with HF. In cross-sectional analyses, compared with no MetS and no diabetes, MetS only (odds ratio [OR], 1.24 [95% CI, 1.10-1.41]) and MetS with diabetes (OR, 1.59 [95% CI, 1.32-1.92]) were associated with elevated Gal-3. Over a median follow-up of 20.5 years, there were 1749 HF events. Compared with individuals with neither diabetes nor MetS and with Gal-3 in the lowest quartile, the combination of MetS with diabetes and Gal-3 ≥75th percentile was associated with a 4-fold higher HF risk (hazard ratio, 4.35 [95% CI, 3.30-5.73]). Gal-3 provided HF prognostic information above and beyond MetS, NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T, and CRP (C-reactive protein) (ΔC statistic for models with versus without Gal-3: 0.003; P =0.004)., Conclusions: MetS and diabetes are associated with elevated Gal-3. The HF risk significantly increased with the combination of greater metabolic risk and higher Gal-3.

Background: Among patients with heart failure (HF), fatigue is common and linked to quality of life and functional status. Fatigue is hypothesized to manifest as multiple types, with general and exertional components. Unique subtypes of fatigue in HF may require differential assessment and treatment to improve outcomes. We conducted this study to identify fatigue subtypes in persons with prevalent HF in the ARIC study (Atherosclerosis Risk in Communities) and describe the distribution of characteristics across subtypes., Methods: We performed a cross-sectional analysis of 1065 participants with prevalent HF at ARIC visit 5 (2011-2013). We measured exertional fatigue using the Modified Medical Research Council Breathlessness scale and general fatigue using the Patient Reported Outcomes Measurement Information System fatigue scale. We used latent class analysis to identify subtypes of fatigue. Number of classes was determined using model fit statistics, and classes were interpreted and assigned fatigue severity rating based on the conditional probability of endorsing survey items given class. We compared characteristics across classes using multinomial regression., Results: Overall, participants were 54% female and 38% Black with a mean age of 77. We identified 4 latent classes (fatigue subtypes): (1) high general/high exertional fatigue (18%), (2) high general/low exertional fatigue (27%), (3) moderate general/moderate exertional fatigue (20%), and (4) low/no general and exertional fatigue (35%). Female sex, Black race, lower education level, higher body mass index, increased depressive symptoms, and higher prevalence of diabetes were associated with higher levels of general and exertional fatigue., Conclusions: We identified unique subtypes of fatigue in patients with HF who have not been previously described. Within subtype, general and exertional fatigue were mostly concordant in severity, and exertional fatigue only occurred in conjunction with general fatigue, not alone. Further understanding these fatigue types and their relationships to outcomes may enhance our understanding of the symptom experience and inform prognostication and secondary prevention efforts for persons with HF., Competing Interests: Disclosures None.

Background: Diabetes exerts adverse effects on the heart, and a longer diabetes duration is associated with greater heart failure risk. We studied diabetes duration and subclinical myocardial injury, as reflected by high-sensitivity cardiac troponin (hs-cTnT)., Methods: We analyzed 9052 participants without heart failure or coronary heart disease (mean age 63 years, 58% female, 21% Black, 15% with diabetes) at The Atherosclerosis Risk in Communities Study (ARIC) Visit 4 (1996 to 1998). Diabetes duration was calculated based on diabetes status at Visits 1 (1987 to 1989) through 4, or using self-reported age of diabetes diagnosis prior to Visit 1. We used multinomial logistic regression to determine the association of diabetes duration with increased (≥14 ng/L) or detectable (≥6 ng/L) Visit 4 hs-cTnT, relative to undetectable hs-cTnT, adjusted for demographics and cardiovascular risk factors., Results: The prevalence of increased Visit 4 hs-cTnT was higher in persons with longer diabetes duration, from 12% for those with diabetes 0 to <5 years up to 31% among those with diabetes for ≥15 years (P for trend <0.0001). New onset diabetes at Visit 4 was associated with 1.92× higher relative risk (95% CI, 1.27-2.91) of increased hs-cTnT than no diabetes. Longer diabetes duration was associated with greater myocardial injury, with duration ≥15 years associated with 9.29× higher risk (95% CI, 5.65-15.29) for increased hs-cTnT and 2.07× (95% CI, 1.24-3.16) for detectable hs-cTnT, compared to no diabetes., Conclusions: Longer diabetes duration is strongly associated with subclinical myocardial injury. Interventional studies are needed to assess whether the prevention and delay of diabetes onset can mitigate early myocardial damage., (© American Association for Clinical Chemistry 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: More than 80% of adult patients diagnosed with cancer survive long term. Long-term complications of cancer and its therapies may increase the risk of cardiovascular disease (CVD), but prospective studies using adjudicated cancer and CVD events are lacking., Objectives: The aim of this study was to assess the risk of CVD in cancer survivors in a prospective community-based study., Methods: We included 12,414 ARIC (Atherosclerosis Risk In Communities) study participants. Cancer diagnoses were ascertained via linkage with state registries supplemented with medical records. Incident CVD outcomes were coronary heart disease (CHD), heart failure (HF), stroke, and a composite of these. We used multivariable Poisson and Cox regressions to estimate the association of cancer with incident CVD., Results: Mean age was 54 years, 55% were female, and 25% were Black. A total of 3,250 participants (25%) had incident cancer over a median 13.6 years of follow-up. Age-adjusted incidence rates of CVD (per 1,000 person-years) were 23.1 (95% CI: 24.7-29.1) for cancer survivors and 12.0 (95% CI: 11.5-12.4) for subjects without cancer. After adjustment for cardiovascular risk factors, cancer survivors had significantly higher risks of CVD (HR: 1.37; 95% CI: 1.26-1.50), HF (HR: 1.52; 95% CI: 1.38-1.68), and stroke (HR: 1.22; 95% CI: 1.03-1.44), but not CHD (HR: 1.11; 95% CI: 0.97-1.28). Breast, lung, colorectal, and hematologic/lymphatic cancers, but not prostate cancer, were significantly associated with CVD risk., Conclusions: Compared with persons without cancer, adult cancer survivors have significantly higher risk of CVD, especially HF, independent of traditional cardiovascular risk factors. There is an unmet need to define strategies for CVD prevention in this high-risk population., Competing Interests: Funding Support and Author Disclosures The ARIC study has been supported with federal funds from the National Heart, Lung, and Blood Institute (NHLBI), the National Institutes of Health (NIH), and the Department of Health and Human Services under contract numbers 75N92022D00001, 75N92022D00002, 75N92022D00003, 75N92022D00004, and 75N92022D00005. Studies on cancer in the ARIC study are also supported by the National Cancer Institute (grant U01CA164975). This research was additionally supported by a Cancer Center Support Grant from the National Cancer Institute (grant P30 CA006973). Ms Daya was supported by NIH/NHLBI grant T32HL007024. Dr Selvin was supported by NIH/National Institute of Diabetes and Digestive and Kidney Diseases grants K24 HL152440 and R01 DK089174. Dr Ndumele was supported by NIH/NHLBI grant R01 HL146907 and American Heart Association grant 20SFRN35120152. The 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: The influence of diabetes on progression from preclinical heart failure (HF) stages to overt HF is poorly understood., Objectives: The purpose of this study was to characterize the influence of diabetes on the progression from preclinical HF stages (A or B based on the 2021 Universal Definition) to overt HF., Methods: We included 4,774 adults with preclinical HF (stage A [n = 1,551] or B [n = 3,223]) who attended the ARIC (Atherosclerosis Risk In Communities) study Visit 5 (2011-2013). Within each stage (A or B), we assessed the associations of diabetes and glycemic control (hemoglobin A 1C [HbA 1C ] <7% vs ≥7%) with progression to HF, and of cross-categories of HF stages (A vs B), diabetes, and glycemic control with incident HF., Results: Among the participants (mean age 75.4 years, 58% women, 20% Black), there were 470 HF events during 8.6 years of follow-up. Stage B participants with HbA 1C  ≥7% experienced clinical HF at a younger age than those with controlled diabetes or without diabetes (mean age 80 years vs 83 years vs 82 years; P < 0.001). HbA 1C  ≥7% was more strongly associated with HF in stage B (HR: 1.83; 95% CI: 1.33-2.51) compared with stage A (HR: 1.52; 95% CI: 0.53-4.38). In cross-categories of preclinical HF stage and HbA 1C , participants with stage B and HbA 1C  ≥7% had increased risk of HF progression compared with stage A without diabetes (HR: 7.56; 95% CI: 4.68-12.20)., Conclusions: Among older adults with preclinical HF stages, uncontrolled diabetes was associated with substantial risk of HF progression. Our results suggest that targeting diabetes early in the HF process is critical., Competing Interests: Funding Support and Author Disclosures The ARIC study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Department of Health and Human Services, under Contract nos. (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I). Dr Echouffo-Tcheugui was supported by NIH/NHLBI grant K23 HL153774. Dr Ndumele was supported by NIH grant R01HL146907. Dr Shah was supported by NIH/NHLBI grants R01HL135008, R01HL143224, R01HL150342, R01HL148218, and K24HL152008; has received research support not related to this study from Novartis and Philips Ultrasound; and has received consulting fees from Philips Ultrasound and Edwards Lifesciences. Dr Selvin was supported by NIH/NHLBI grant K24 HL152440 and NIH/NIDDK grant R01DK089174; and has received payments from Wolters Kluwer for chapters and laboratory monographs in UpToDate on measurements of glycemic control and screening tests for type 2 diabetes. The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 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 Laboratory data suggest obesity is linked to myocardial inflammation and fibrosis, but clinical data are limited. We aimed to examine the association of obesity with galectin-3, a biomarker of cardiac inflammation and fibrosis, and the related implications for heart failure (HF) risk. Methods and Results We evaluated 8687 participants (mean age 63 years; 21% Black) at ARIC (Atherosclerosis Risk in Communities) Visit 4 (1996-1998) who were free of heart disease. We used adjusted logistic regression to estimate the association of body mass index (BMI) categories with elevated galectin-3 (≥75th sex-specific percentile) overall and across demographic subgroups, with tests for interaction. We used Cox proportional hazards models to assess the combined associations of galectin-3 and BMI with incident HF (through December 31, 2019). Higher BMI was associated with higher odds of elevated galectin-3 (odds ratio [OR], 2.32; 95% CI, 1.88-2.86) for severe obesity ([BMI ≥35 kg/m 2 ] versus normal weight [BMI 18.5-<25 kg/m 2 ]). There were stronger associations of BMI with elevated galectin-3 among women versus men and White versus Black participants (both P -for-interaction <0.05). Elevated galectin-3 was similarly associated with incident HF among people with and without obesity (HR, 1.49; 95% CI, 1.18-1.88; and HR, 1.71; 95% CI, 1.38-2.11, respectively). People with severe obesity and elevated galectin-3 had >4-fold higher risk of HF (HR, 4.19; 95% CI, 2.98-5.88) than those with normal weight and galectin-3 <25th percentile. Conclusions Obesity is strongly associated with elevated galectin-3. Additionally, the combination of obesity and elevated galectin-3 is associated with marked HF risk, underscoring the importance of elucidating pathways linking obesity with cardiac inflammation and fibrosis.

Angiotensin receptor-neprilysin inhibitors (ARNIs) greatly benefit functional capacity and longevity in heart failure with reduced ejection fraction (HFrEF). Angiotensin receptor-neprilysin inhibitors remain underutilized and unstudied, however, in left ventricular assist device (LVAD) recipients, in spite of their underlying HFrEF. In this case series, we studied the feasibility and short-term efficacy of ARNI utilization in 21 LVAD patients. Angiotensin receptor-neprilysin inhibitor initiation was successful in most, resulting in significant consolidation of blood pressure (BP) medical management and marked improvements in both functional capacity and diuretic requirements. Angiotensin receptor-neprilysin inhibitors are safe, feasible, and within a short timeframe benefit BP and heart failure control in LVAD recipients., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

Objectives: This study assessed the association of diabetes duration with incident heart failure (HF)., Background: Diabetes increases HF risk. However, the independent effect of diabetes duration on incident HF is unknown., Methods: We included 9,734 participants (mean age 63 years, 58% women, 22% Black) at ARIC (Atherosclerosis Risk In Communities) Visit 4 (1996-1998) without HF or coronary heart disease. We calculated diabetes duration at Visit 4 (baseline), utilizing diabetes status at the first 4 ARIC visits spaced 3 years apart, and self-reported diagnosis date for those with diabetes diagnosed before Visit 1. We used Cox regression to estimate associations of diabetes duration with incident HF, accounting for intercurrent coronary heart disease and other risk factors. We performed analyses stratified by age (<65 years or ≥65 years), race, sex, and glycemic control (hemoglobin A 1C [HbA 1C ] consistently <7%, vs HbA 1C  ≥7%), with tests for interaction., Results: Over 22.5 years of follow-up, there were 1,968 HF events. Compared to those without diabetes, HF risk rose with longer diabetes duration, with the highest risk among those with ≥15 y diabetes duration (HR: 2.82; 95% CI: 2.25-3.63). Each 5-year increase in diabetes duration was associated with a 17% (95% CI: 11-22) relative increase in HF risk. Similar results were observed across HF subtypes. The HF and diabetes duration associations were stronger among those aged <65 years, those with HbA 1C  ≥7%, those with a body mass index ≥30 kg/m 2 , women, and Blacks (all P interactions <0.05)., Conclusions: Delaying diabetes onset may augment HF prevention efforts, and therapies to improve HF outcomes might target those with long diabetes duration., Competing Interests: Funding Support and Author Disclosures The ARIC study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), and Department of Health and Human Services, under Contract nos. HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I. The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Tcheugui was supported by National Institutes of Health (NIH)/NHLBI grant K23 HL153774. Dr Hamo was supported by NIH/NHLBI grant number T32 HL007024. Dr Selvin was supported by NIH/National Institute of Diabetes and Digestive and Kidney Diseases grants K24 HL152440 and R01DK089174, and American Heart Association grant 20SFRN35120152. Dr Ndumele was supported by NIH grant R01HL146907 and American Heart Association grant 20SFRN35120152. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background Greater physical activity (PA) is associated with lower heart failure (HF) risk. However, it is unclear whether this inverse association exists across all subgroups at high risk for HF, particularly among those with preexisting atherosclerotic cardiovascular disease. Methods and Results We followed 13 810 ARIC (Atherosclerosis Risk in Communities) study participants (mean age 55 years, 54% women, 26% black) without HF at baseline (visit 1; 1987-1989). PA was assessed using a modified Baecke questionnaire and categorized according to American Heart Association guidelines: recommended, intermediate, or poor. We constructed Cox models to estimate associations between PA categories and incident HF within each high-risk subgroup at baseline, with tests for interaction. We performed additional analyses modeling incident coronary heart disease as a time-varying covariate. Over a median of 26 years of follow-up, there were 2994 HF events. Compared with poor PA, recommended PA was associated with lower HF risk among participants with hypertension, obesity, diabetes mellitus, and metabolic syndrome (all P <0.01), but not among those with prevalent atherosclerotic cardiovascular disease (coronary heart disease, stroke, or peripheral arterial disease) (hazard ratio, 0.91; 95% CI, 0.74-1.13 [ P interaction=0.02]). Recommended PA was associated with lower risk of incident coronary heart disease (hazard ratio, 0.79; 95% CI, 0.72-0.86), but not with lower HF risk in those with interim coronary heart disease events (hazard ratio, 0.90; 95% CI, 0.78-1.04 [ P interaction=0.04]). Conclusions PA was associated with decreased HF risk in patients with hypertension, obesity, diabetes mellitus, and metabolic syndrome. Despite a myriad of benefits in patients with atherosclerotic cardiovascular disease, PA may have weaker associations with HF prevention after ischemic disease is established.

Background Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is characterized by high arrhythmic burden and progressive heart failure, which can prompt referral for heart transplantation. Cardiopulmonary exercise testing (CPET) has an established role in risk stratification for advanced heart failure therapies, but has not been described in ARVC/D. This study sought to determine the safety and prognostic utility of CPET in patients with ARVC/D. Methods and Results Using the Johns Hopkins ARVC/D Registry, we examined patients with ARVC/D undergoing CPET. Baseline characteristics and transplant-free survival were compared on the basis of peak oxygen consumption (pVO2) (≤14 or >14 mL/kg per minute) and ventilatory efficiency (Ve/VCO 2 slope ≤34 or >34). Thirty-eight patients underwent 50 CPETs. There were no sustained arrhythmic events. Twenty-nine patients achieved a maximal test. Patients with pVO2 ≤14 mL/kg per minute were more often men ( P =0.042) compared with patients with pVO2 >14 mL/kg per minute. Patients with Ve/VCO 2 slope >34 tended to have more moderate/severe right ventricular dilation (7/9 [78%] versus 10/26 [38%]; P =0.060) and clinical heart failure (8/9 [89%] versus 13/26 [50%]; P =0.056) compared with patients with Ve/VCO 2 slope ≤34. Patients who underwent heart transplantation were more likely to have clinical heart failure (10/10 [100%] versus 13/28 [46%]; P =0.003). Patients with Ve/VCO 2 slope >34 had worse transplant-free survival compared with patients with Ve/VCO 2 slope ≤34 (n=35; hazard ratio, 6.57 [95% CI, 1.28-33.72]; log-rank P =0.010), whereas transplant-free survival was similar on the basis of pVO2 groups (n=29; hazard ratio, 3.38 [95% CI, 0.75-15.19]; log-rank P =0.092). Conclusions CPET is safe to perform in patients with ARVC/D. Ve/VCO 2 slope may be used for risk stratification and guide referral for heart transplantation in ARVC/D.

Introduction: Physical activity (PA) is inversely associated with risk of heart failure and cardiovascular disease (CVD), whereas increased left ventricular (LV) mass and mass to volume (m:v) ratio are unfavorable CVD risk factors. We assessed whether changes in leisure time PA were associated with longitudinal changes in cardiac structure in a community-based population., Methods: We included 2779 Multi-Ethnic Study of Atherosclerosis participants, free of baseline CVD, who had available data on PA and cardiac magnetic resonance imaging at examinations 1 (2000-2002) and 5 (2010-2012). Physical activity was measured by a Typical Week PA Survey and converted to MET-minutes per week of moderate+vigorous activity. We used linear mixed effect models to estimate the associations of baseline and change in PA with baseline and change in cardiac structure, adjusting for CVD risk factors and body size., Results: At baseline, the mean age was 59 yr, 53% were women, and 58% of nonwhite race/ethnicity. During average 10-yr follow-up, and after accounting for baseline PA levels, the highest quintiles of PA increase were significantly associated with increases in LV mass (2.3 g; 95% confidence interval [CI], 0.4-4.2), LV end-diastolic volume (4.7 mL; 95% CI, 2.4-7.0), and stroke volume (3.3 mL; 95% CI, 1.6-5.1), but lower M:V ratio (-2.9; 95% CI, -5.0 to -0.8) compared with the lowest quintiles. Increasing exercise PA was associated with increases in LV diameter and reductions in M:V ratio, whereas occupational PA was associated with increases in m:v ratio. Increasing PA over 10 yr was also associated with greater risk of eccentric dilated LV hypertrophy at examination 5., Conclusions: After accounting for baseline PA, greater positive changes in leisure-time PA levels were associated with a more eccentric-type of LV remodeling pattern over 10 yr. The clinical implications of such findings remain to be determined.

Background: Higher physical activity (PA) is associated with lower heart failure (HF) risk; however, the effect of changes in PA on HF risk is unknown., Methods: We evaluated 11 351 ARIC study (Atherosclerosis Risk in Communities) participants (mean age 60 years) who attended visit 3 (1993-1995) and did not have a history of cardiovascular disease. Exercise PA was assessed using a modified Baecke questionnaire and categorized according to American Heart Association guidelines as recommended, intermediate, or poor. We used Cox regression models to characterize the association of 6-year changes in PA between the first (1987-1989) and third ARIC visits and HF risk., Results: During a median of 19 years of follow-up, 1750 HF events occurred. Compared with those with poor activity at both visits, the lowest HF risk was seen for those with persistently recommended activity (hazard ratio, 0.69; 95% confidence interval, 0.60-0.80). However, those whose PA increased from poor to recommended also had reduced HF risk (hazard ratio, 0.77; 95% confidence interval 0.63-0.93). Among participants with poor baseline activity, each 1 SD higher PA at 6 years (512.5 METS*minutes/week, corresponding to ≈30 minutes of brisk walking 4 times per week) was associated with significantly lower future HF risk (hazard ratio, 0.89, 95% confidence interval, 0.82-0.96)., Conclusions: Although maintaining recommended activity levels is associated with the lowest HF risk, initiating and increasing PA, even in late middle age, are also linked to lower HF risk. Augmenting PA may be an important component of strategies to prevent HF., (© 2018 American Heart Association, Inc.)

Left ventricular assist device (LVAD) implantation and survival is increasing. With patients living longer on device support, LVAD-related healthcare costs and hospitalizations, including those for volume overload, are on the rise as well. The Johns Hopkins Heart Failure Bridge Clinic (HFBC), a HF-trained Nurse Practitioner (NP) led clinic with ability to administer outpatient intravenous (IV) diuretics, has resulted in significant reductions in HF readmission rates. We developed a protocol for LVAD patient assessment and management via the HFBC, and describe our initial experience regarding the role and efficacy of this unique program in outpatient management of HF in LVAD patients. LVAD patients were evaluated by an LVAD provider and subsequently referred to the diuresis clinic for volume overload thought not to be related to an LVAD issue. If seen in the diuresis clinic, patients then had repeat evaluation with the LVAD/HF team within one week. Baseline characteristics and HF outcomes were assessed. Nineteen LVAD patients were seen in the diuresis clinic a total of 65 times. IV furosemide was administered 31 times to 13 patients (mean dose 80 ± 23.5 mg). Urine output during first in clinic void after IV diuretic was 125 ± 53 mL. At 30 of 65 (46%) visits, oral diuretic dose was uptitrated. Potassium was given at 18 of the 65 (27.7%) visits. There were no significant changes in blood pressure, renal function, or electrolytes post diuresis. Only 1 of 65 patient visits resulted in direct hospital admission (hyponatremia). All other visits discharged to home in improved/stable condition and avoidance of hospitalization for heart failure. During follow up, only 6 of 19 patients were hospitalized for a primary diagnosis of volume overload. We describe successful implementation of an outpatient IV diuresis protocol for treatment of HF in LVAD patients. The strategy has major implications in reducing LVAD-related HF hospitalizations and healthcare utilization [ABSTRACT FROM AUTHOR]

Angiotensin receptor neprilysin inhibitors (ARNIs) are not routinely used in patients following left ventricular assist device (LVAD) implantation. At our center, we have increasingly adopted ARNI use in LVAD patients. The objective of this study was to investigate the effects of ARNI therapy on LVAD patients. Stable LVAD outpatients with hypertension and persistent heart failure symptoms were initiated on ARNI therapy at our center. We retrospectively reviewed medication requirements and clinical parameters pre- and 3-months post-ARNI initiation. Twenty stable LVAD outpatients were initiated on sacubitril-valsartan in an effort to improve blood pressure control and heart failure symptoms. Of these 20 patients, 10 (50%) were maintained on 24/26 mg BID dosing, 6 (30%) were uptitrated to 49/51 mg BID, and 4 (20%) to 97/103 mg BID. Three months following ARNI initiation, mean arterial pressure improved from 92±24 to 75±19 mm Hg (P<0.001). ARNI allowed for significant dose reduction in calcium channel blocker dose burden (nifedipine 56±60 to 30±48 mg/day, P=0.02; amlodipine 3±4 to 0±2 mg/day, P=0.06). ARNI also facilitated a significant reduction in loop diuretic requirement (furosemide equivalent of 132±136 to 80±65.6 mg/day, P=0.004). There was an overall improvement in New York Heart Association Functional Class (2.6±0.8 to 1.6±0.7, P<0.001). Renal function did not appreciably change (Creatinine 1.3±0.5 to 1.3±0.3 mg/dl, P=0.76). There was a trend towards reduced left ventricular diastolic diameter (6.1±1.0 to 5.7±1.1 cm, P=0.13). Six patients experienced an unremitting side effect requiring ARNI cessation (dizziness/hypotension, 3; LVAD suction, 2; cough, 1). ARNI can improve blood pressure, decrease diuretic requirement, and improve functional capacity in LVAD patients. LVAD speed and medication adjustments may be necessary following ARNI initiation, and in some instances, side effects can limit the ability to sustain ARNI therapy in the setting of LVAD. [ABSTRACT FROM AUTHOR]