Novel Trial Design: CHIEF-HF.

BACKGROUND: The expense of clinical trials mandates new strategies to efficiently generate evidence and test novel therapies. In this context, we designed a decentralized, patient-centered randomized clinical trial leveraging mobile technologies, rather than in-person site visits, to test the efficacy of 12 weeks of canagliflozin for the treatment of heart failure, regardless of ejection fraction or diabetes status, on the reduction of heart failure symptoms. METHODS: One thousand nine hundred patients will be enrolled with a medical record-confirmed diagnosis of heart failure, stratified by reduced (≤40%) or preserved (>40%) ejection fraction and randomized 1:1 to 100 mg daily of canagliflozin or matching placebo. The primary outcome will be the 12-week change in the total symptom score of the Kansas City Cardiomyopathy Questionnaire. Secondary outcomes will be daily step count and other scales of the Kansas City Cardiomyopathy Questionnaire. RESULTS: The trial is currently enrolling, even in the era of the coronavirus disease 2019 (COVID-19) pandemic. CONCLUSIONS: CHIEF-HF (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure) is deploying a novel model of conducting a decentralized, patient-centered, randomized clinical trial for a new indication for canagliflozin to improve the symptoms of patients with heart failure. It can model a new method for more cost-effectively testing the efficacy of treatments using mobile technologies with patient-reported outcomes as the primary clinical end point of the trial. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04252287.

COVID-19 myocarditis and long-term heart failure sequelae.

PURPOSE OF REVIEW: The clinical syndrome of coronavirus disease 2019 (COVID-19) has become a global pandemic leading to significant morbidity and mortality. Cardiac dysfunction is commonly seen in these patients, often presenting as clinical heart failure. Accordingly, we aim to provide a comprehensive review on COVID-19 myocarditis and its long-term heart failure sequelae. RECENT FINDINGS: Several suspected cases of COVID-19 myocarditis have been reported. It is often not clear if the acute myocardial dysfunction is caused by myocarditis or secondary to generalized inflammatory state of cytokine release or microvascular thrombotic angiopathy. Ischemia may also need to be ruled out. Regardless, myocardial dysfunction in these patients is associated with poor overall prognosis. Laboratory testing, echocardiography, cardiac magnetic resonance imaging, and even endomyocardial biopsy may be needed for timely diagnosis. Several treatment strategies have been described, including both supportive and targeted therapies. SUMMARY: COVID-19 can cause a spectrum of ventricular dysfunction ranging from mild disease to fulminant myocarditis with hemodynamic instability. Future research is needed to understand the true prevalence of COVID-19 myocarditis, as well as to better define various diagnostic protocols and treatment strategies.

Efficacy of implantable haemodynamic monitoring in heart failure across ranges of ejection fraction: a systematic review and meta-analysis.

AIMS: We conducted a meta-analysis of randomised controlled trials (RCTs) of implantable haemodynamic monitoring (IHM)-guided care. METHODS: PubMed and Ovid MEDLINE were searched for RCTs of IHM in patients with heart failure (HF). Outcomes were examined in total (first and recurrent) event analyses. RESULTS: Five trials comparing IHM-guided care with standard care alone were identified and included 2710 patients across ejection fraction (EF) ranges. Data were available for 628 patients (23.2%) with heart failure with preserved ejection fraction (HFpEF) (EF ≥50%) and 2023 patients (74.6%) with heart failure with a reduced ejection fraction (HFrEF) (EF <50%). Chronicle, CardioMEMS and HeartPOD IHMs were used. In all patients, regardless of EF, IHM-guided care reduced total HF hospitalisations (HR 0.74, 95% CI 0.66 to 0.82) and total worsening HF events (HR 0.74, 95% CI 0.66 to 0.84). In patients with HFrEF, IHM-guided care reduced total worsening HF events (HR 0.75, 95% CI 0.66 to 0.86). The effect of IHM-guided care on total worsening HF events in patients with HFpEF was uncertain (fixed-effect model: HR 0.72, 95% CI 0.59 to 0.88; random-effects model: HR 0.60, 95% CI 0.32 to 1.14). IHM-guided care did not reduce mortality (HR 0.92, 95% CI 0.71 to 1.20). IHM-guided care reduced all-cause mortality and total worsening HF events (HR 0.80, 95% CI 0.72 to 0.88). CONCLUSIONS: In patients with HF across all EFs, IHM-guided care reduced total HF hospitalisations and worsening HF events. This benefit was consistent in patients with HFrEF but not consistent in HFpEF. Further trials with pre-specified analyses of patients with an EF of ≥50% are required. PROSPERO REGISTRATION NUMBER: CRD42021253905.

Acute heart failure due to COVID-19 related myocardial injury and de novo hypertensive cardiomyopathy: a challenging diagnosis.

We report a COVID-19 case with acute heart and kidney failure in a healthy young male. Echocardiography showed severe systolic and diastolic left ventricle dysfunction, with diffuse myocardial thickening. Cardiac MRI showed aspects of focal myocarditis, and hypertensive cardiomyopathy. Renal biopsy demonstrated limited acute tubular injury, and hypertensive kidney disease. Coronary angiography excluded critical stenoses. Unlike what we initially suspected, myocardial inflammation had a limited extent in our patient; severe hypertension causing cardiomyopathy and multi-organ damage, not diagnosed before, was primarily responsible for severe illness. Correct diagnosis and guidelines-directed treatment allowed a favorable course.

Recent Advances in Remote Pulmonary Artery Pressure Monitoring for Patients with Chronic Heart Failure: Current Evidence and Future Perspectives.

Chronic heart failure (HF) is associated with high hospital admission rates and has an enormous burden on hospital resources worldwide. Ideally, detection of worsening HF in an early phase would allow physicians to intervene timely and proactively in order to prevent HF-related hospitalizations, a concept better known as remote hemodynamic monitoring. After years of research, remote monitoring of pulmonary artery pressures (PAP) has emerged as the most successful technique for ambulatory hemodynamic monitoring in HF patients to date. Currently, the CardioMEMS and Cordella HF systems have been tested for pulmonary artery pressure monitoring and the body of evidence has been growing rapidly over the past years. However, several ongoing studies are aiming to fill the gap in evidence that is still very clinically relevant, especially for the European setting. In this comprehensive review, we provide an overview of all available evidence for PAP monitoring as well as a detailed discussion of currently ongoing studies and future perspectives for this promising technique that is likely to impact HF care worldwide.

Rethinking heart failure: patient classification and treatment.

INTRODUCTION: Approaches to treating heart failure (HF), understanding of the most timely and effective interventions, and identification of appropriate patient subpopulations must evolve. HF has emerged as a chronic condition that needs to be managed on multiple fronts. Hospital resources are more limited than ever due to various factors that directly impact staff and hospital space available to manage and treat patients with HF. As a result, there is increasing attention to the current state of this progressive disease and ways to improve patient outcomes. PURPOSE: This paper examines HF and the current and future treatment landscape, the need to reevaluate terms and definitions, and the opportunity to treat HF with the right treatment at the right time. Treatments in development and potential new investigational therapies are also discussed. CONCLUSION: To meet the current challenge, HF treatment must adapt. For other disease states, we have more personalized, nimble, and timely treatment strategies that harness windows of opportunity to help maximize outcomes and reduce overwhelming costs to the health care system. HF treatment is evolving with new guidelines and treatments that hold the promise of greater personalization through additions to existing treatments that are directed by medical guidelines, since each patient is unique and requires more than a one-size-fits-all approach. In addition, advances in remote monitoring, in-home care, and telemedicine are creating a more individualized treatment approach. Therefore, it becomes critical for all health care decision makers to be aware of the tools and resources available in treatment guidelines, individualized treatment options, telemedicine, and other ways of expanding the existing toolbox to enhance patient centricity in HF treatment.

The Effect of COVID-19 on Long-Term Cardiac Function in Patients With Chronic Heart Failure.

Aim      To evaluate functional changes in the heart in the long-term following COVID-19 in patients with chronic heart failure (CHF).Material and methods  Case reports of 54 patients aged 69.1±9.7 years who had COVID-19 from January 2021 through January 2022 and had been previously diagnosed with NYHA functional class II-III CHF were studied. Two comparison groups were isolated: HF with LV EF >50 % (n=39) and <50 % (n=15). Echocardiography was used to evaluate changes in LV EF and pulmonary artery systolic pressure (PASP) 5-6 months following COVID-19.Results In all CHF patients after COVID-19 at 5.8 months on average, LV EF decreased (median difference, 2.5 %; 95 % confidence interval (CI): 6.99×10-5- 4.99) and PASP increased (median difference, 8 mm Hg; 95 % CI: 4.5-12.9). In the HF group with LV EF <50 %, the decrease in EF was greater than in the group with LV EF >50 % (6.9 and 0.7 %, respectively; p=0.037); furthermore, the CHF phenotype did not influence the change in PASP (p=0.4). The one-factor regression analysis showed that the dynamics of LV EF decrease was significantly influenced by the baseline decrease in LV EF, whereas the change in PASP was influenced by the dynamics of LV EF decrease, presence of dyslipidemia, and statin treatment. Furthermore, the multifactorial analysis showed that prognostically significant factors for long-term changes in LV EF following COVID-19 were male gender (odds ratio (OR), 5.92; 95 % CI: 1.31-26.75; p=0.014), LV EF at baseline <50 % (OR, 0.88; 95 % CI: 0.8-0.96; p<0.001); changes in PASP depended on the presence of dyslipidemia (OR, 0.08; 95 % CI: 0.01-0.84; p=0.018).Conclusion      This study showed that COVID-19 in the long term can influence the course of CHF; in this process, HF patients with EF <50 % have progression of systolic dysfunction and PASP, whereas patients with EF >50 % have an isolated increase in PASP.

Proteomic profiling of epicardial fat in heart failure with preserved versus reduced and mildly reduced ejection fraction.

In order to explore the proteomic signatures of epicardial adipose tissue (EAT) related to the mechanism of heart failure with reduced and mildly reduced ejection fraction (HFrEF/HFmrEF) and heart failure (HF) with preserved ejection fraction (HFpEF), a comprehensive proteomic analysis of EAT was made in HFrEF/HFmrEF (n = 5) and HFpEF (n = 5) patients with liquid chromatography-tandem mass spectrometry experiments. The selected differential proteins were verified between HFrEF/HFmrEF (n = 20) and HFpEF (n = 40) by ELISA (enzyme-linked immunosorbent assay). A total of 599 EAT proteins were significantly different in expression between HFrEF/HFmrEF and HFpEF. Among the 599 proteins, 58 proteins increased in HFrEF/HFmrEF compared to HFpEF, whereas 541 proteins decreased in HFrEF/HFmrEF. Of these proteins, TGM2 in EAT was down-regulated in HFrEF/HFmrEF patients and was confirmed to decrease in circulating plasma of the HFrEF/HFmrEF group (p = 0.019). Multivariate logistic regression analysis confirmed plasma TGM2 could be an independent predictor of HFrEF/HFmrEF (p = 0.033). Receiver operating curve analysis indicated that the combination of TGM2 and Gensini score improved the diagnostic value of HFrEF/HFmrEF (p = 0.002). In summary, for the first time, we described the proteome in EAT in both HFpEF and HFrEF/HFmrEF and identified a comprehensive dimension of potential targets for the mechanism behind the EF spectrum. Exploring the role of EAT may offer potential targets for preventive intervention of HF.

Natriuretic Peptides as Biomarkers: Narrative Review and Considerations in Cardiovascular and Respiratory Dysfunctions.

Natriuretic peptides (NPs) encompass a family of structurally related hormone/paracrine factors acting through the natriuretic peptide system regulating cell proliferation, vessel tone, inflammatory processes, neurohumoral pathways, fluids, and electrolyte balance. The three most studied peptides are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-Type natriuretic peptide (CNP). ANP and BNP are the most relevant NPs as biomarkers for the diagnosis and prognosis of heart failure and underlying cardiovascular diseases, such as cardiac valvular dysfunction, hypertension, coronary artery disease, myocardial infarction, persistent arrhythmias, and cardiomyopathies. Cardiac dysfunctions related to cardiomyocytes stretching in the atria and ventricles are primary elicitors of ANP and BNP release, respectively. ANP and BNP would serve as biomarkers for differentiating cardiac versus noncardiac causes of dyspnea and as a tool for measuring the prognosis of patients with heart failure; nevertheless, BNP has been shown with the highest predictive value, particularly related to pulmonary disorders. Plasma BNP has been reported to help differentiate cardiac from pulmonary etiologies of dyspnea in adults and neonates. Studies have shown that COVID-19 infection also increases serum levels of N-terminal pro b-type natriuretic peptide (NT-proBNP) and BNP. This narrative review assesses aspects of ANP and BNP on their physiology, and predictive values as biomarkers. We present an overview of the NPs' synthesis, structure, storage, and release, as well as receptors and physiological roles. Following, considerations focus on ANP versus BNP, comparing their relevance in settings and diseases associated with respiratory dysfunctions. Finally, we compiled data from guidelines for using BNP as a biomarker in dyspneic patients with cardiac dysfunction, including its considerations in COVID-19.

Frequency and Type of Outpatient Visits for Patients With Cardiovascular Ambulatory-Care Sensitive Conditions During the COVID-19 Pandemic and Subsequent Outcomes: A Retrospective Cohort Study.

Background Because the impact of changes in how outpatient care was delivered during the COVID-19 pandemic is uncertain, we designed this study to examine the frequency and type of outpatient visits between March 1, 2019 to February 29, 2020 (prepandemic) and from March 1, 2020 to February 28, 2021 (pandemic) and specifically compared outcomes after virtual versus in-person outpatient visits during the pandemic. Methods and Results Population-based retrospective cohort study of all 3.8 million adults in Alberta, Canada. We examined all physician visits and 30- and 90-day outcomes, with a focus on those adults with the cardiovascular ambulatory-care sensitive conditions heart failure, hypertension, and diabetes. Our primary outcome was emergency department visit or hospitalization, evaluated using survival analysis accounting for competing risk of death. Although in-person outpatient visits decreased by 38.9% in the year after March 1, 2020 (10 142 184 versus 16 592 599 in the prior year), the introduction of virtual visits (7 152 147; 41.4% of total) meant that total outpatient visits increased by 4.1% in the first year of the pandemic for Albertan adults. Outpatient visit frequency (albeit 41.4% virtual, 58.6% in-person) and prescribing patterns were stable in the first year after pandemic onset for patients with the cardiovascular ambulatory-care sensitive conditions we examined, but laboratory test frequency declined by 20% (serum creatinine) to 47% (glycosylated hemoglobin). In the first year of the pandemic, virtual outpatient visits were associated with fewer subsequent emergency department visits or hospitalizations (compared with in-person visits) for patients with heart failure (adjusted hazard ratio [aHR], 0.90 [95% CI, 0.85-0.96] at 30 days and 0.96 [95% CI, 0.92-1.00] at 90 days), hypertension (aHR, 0.88 [95% CI, 0.85-0.91] and 0.93 [95% CI, 0.91-0.95] at 30 and 90 days), or diabetes (aHR, 0.90 [95% CI, 0.87-0.93] and 0.93 [95% CI, 0.91-0.95] at 30 and 90 days). Conclusions The adoption and rapid uptake of virtual outpatient care during the COVID-19 pandemic did not negatively impact frequency of follow-up, prescribing, or short-term outcomes, and could have potentially positively impacted some of these for adults with heart failure, diabetes, or hypertension in a setting where there was an active reimbursement policy for virtual visits. Given declines in laboratory monitoring and screening activities, further research is needed to evaluate whether long-term outcomes will differ.

COVID-19, Heart Failure Hospitalizations, and Outcomes: A Nationwide Analysis.

Heart Failure (HF) patients are at a higher risk of adverse events associated with Coronavirus disease 2019 (COVID-19). Large population-based reports of the impact of COVID-19 on patients hospitalized with HF are limited. The National Inpatient Sample database was queried for HF admissions during 2020 in the United States (US), with and without a diagnosis of COVID-19 based on ICD-10-CM U07. Propensity score matching was used to match patients across age, race, sex, and comorbidities. Multivariate logistic regression analysis was used to identify predictors of mortality. A weighted total of 1,110,085 hospitalizations for HF were identified of which 7,905 patients (0.71%) had a concomitant diagnosis of COVID-19. After propensity matching, HF patients with COVID-19 had higher rate of in-hospital mortality (8.2% vs 3.7%; odds ratio [OR]: 2.33 [95% confidence interval [CI]: 1.69, 3.21]; P< 0.001), cardiac arrest (2.9% vs 1.1%, OR 2.21 [95% CI: 1.24,3.93]; P<0.001), and pulmonary embolism (1.0% vs 0.4%; OR 2.68 [95% CI: 1.05, 6.90]; P = 0.0329). During hospitalizations for HF, COVID-19 was also found to be an independent predictor of mortality. Further, increasing age, arrythmias, and chronic kidney disease were independent predictors of mortality in HF patients with COVID-19. COVID-19 is associated with increased in-hospital mortality, longer hospital stays, higher cost of hospitalization and increased risk of adverse outcomes in patients admitted with HF.

Longitudinal HbA1c trajectory modelling reveals the association of HbA1c and risk of hospitalization for heart failure for patients with type 2 diabetes mellitus.

BACKGROUND: Inconsistent conclusions in past studies on the association between poor glycaemic control and the risk of hospitalization for heart failure (HHF) have been reported largely due to the analysis of non-trajectory-based HbA1c values. Trajectory analysis can incorporate the effects of HbA1c variability across time, which may better elucidate its association with macrovascular complications. Furthermore, studies analysing the relationship between HbA1c trajectories from diabetes diagnosis and the occurrence of HHF are scarce. METHODS: This is a prospective cohort study of the SingHealth Diabetes Registry (SDR). 17,389 patients diagnosed with type 2 diabetes mellitus (T2DM) from 2013 to 2016 with clinical records extending to the end of 2019 were included in the latent class growth analysis to extract longitudinal HbA1c trajectories. Association between HbA1c trajectories and risk of first known HHF is quantified with the Cox Proportional Hazards (PH) model. RESULTS: 5 distinct HbA1c trajectories were identified as 1. low stable (36.1%), 2. elevated stable (40.4%), 3. high decreasing (3.5%), 4. high with a sharp decline (10.8%), and 5. moderate decreasing (9.2%) over the study period of 7 years. Poorly controlled HbA1c trajectories (Classes 3, 4, and 5) are associated with a higher risk of HHF. Using the diabetes diagnosis time instead of a commonly used pre-defined study start time or time from recruitment has an impact on HbA1c clustering results. CONCLUSIONS: Findings suggest that tracking the evolution of HbA1c with time has its importance in assessing the HHF risk of T2DM patients, and T2DM diagnosis time as a baseline is strongly recommended in HbA1c trajectory modelling. To the authors' knowledge, this is the first study to identify an association between HbA1c trajectories and HHF occurrence from diabetes diagnosis time.

The Utility of Home Sleep Apnea Testing in the Advanced Heart Failure Populations.

Untreated sleep disorders form a risk of coronary artery disease, hypertension, obesity, and diabetes mellitus. Access to polysomnography is limited, especially during the COVID-19 pandemic, with home sleep apnea testing (HSAT) being a potentially viable alternative. We describe an HSAT protocol in patients with advanced heart failure (HF). In a single-center, observational analysis between 2019 and 2021 in patients with advanced HF and heart transplant (HT), 135 screened positive on the STOP-Bang sleep survey and underwent a validated HSAT (WatchPAT, ZOLL-Itamar). HSAT was successful in 123 patients (97.6%), of whom 112 (91.1%; 84 HF and 28 HT) tested positive for sleep apnea. A total of 91% of sleep apnea cases were obstructive, and 63% were moderate to severe. Multivariable linear regression showed that the apnea hypopnea index was 34% lower in the HT group than in the HF group (p = 0.046) after adjusting for gender, and that this effect persisted in White patients but not among African-Americans. Patient characteristics were similar between groups, with coronary artery disease, diabetes mellitus, and hypertension as the most prevalent co-morbidities. In conclusion, sleep apnea remains prevalent in patients with HF with a high co-morbidity burden. HSAT is a feasible and effective tool for screening and diagnosis in this population.

Developing a contemporary community clinic for patients with heart failure with preserved ejection fraction within the current National Health Service model.

INTRODUCTION: The diagnostic and therapeutic arsenal for heart failure with preserved ejection (HFpEF) has expanded. With novel therapies (eg, sodium-glucose co-transporter 2 inhibitors) and firmer recommendations to optimise non-cardiac comorbidities, it is unclear if outpatient HFpEF models can adequately deliver this. We; therefore, evaluated the efficacy of an existing dedicated HFpEF clinic to find innovative ways to design a more comprehensive model tailored to the modern era of HFpEF. METHODS: A single-centre retrospective analysis of 202 HFpEF outpatients was performed over 12 months before the COVID-19 pandemic. Baseline characteristics, clinic activities (eg, medication changes, lifestyle modifications, management of comorbidities) and follow-up arrangements were compared between a HFpEF and general cardiology clinic to assess their impact on mortality and morbidity at 6 and 12 months. RESULTS: Between the two clinic groups, the sample population was evenly matched with a typical HFpEF profile (mean age 79±9.6 years, 55% female and a high prevalence of cardiometabolic comorbidities). While follow-up practices were similar, the HFpEF clinic delivered significantly more interventions on lifestyle changes, blood pressure and heart rate control (p<0.0001) compared with the general clinic. Despite this, no significant differences in all-cause hospitalisation and mortality were observed. This may be attributed to the fact that clinic activities were primarily cardiology-focused. Importantly, non-cardiovascular admissions accounted for >60% of hospitalisation, including causes of recurrent admissions. CONCLUSION: This study suggests that existing general and emerging dedicated HFpEF clinics may not be adequate in addressing the multifaceted aspects of HFpEF as clinic activities concentrated primarily on cardiological measures. Although the small cohort and short follow-up period are important limitations, this study reminds clinicians that HFpEF patients are more at risk of non-cardiac than HF-related events. We have therefore proposed a pragmatic framework that can comprehensively deliver the modern guideline-directed recommendations and management of non-cardiac comorbidities through a multidisciplinary approach.

The Combination Clinical Value of Plasma Brain Natriuretic Peptide and Serum HbAlc in the Diagnosis of Chronic Pulmonary Heart Disease.

Objective: To analyze the combination clinical value of plasma brain natriuretic peptide and serum glycated hemoglobin (HbAlc) in chronic pulmonary heart disease. Methods: A total of 200 patients with chronic pulmonary heart disease admitted to our hospital from January 2021 to January 2022 were selected as the observation group, and 200 healthy subjects were selected as the control group during the same period. All subjects were examined by an ECG vector map and plasma BNP, and HbAlc levels were detected to analyze the value and clinical significance of each index in single diagnosis and combined diagnosis. Results: Plasma BNP and HbAlc levels in the observation group were significantly higher than those in the control group (P < 0.05). There were 154 BNP positive, 146 HbAlc positive, 164 parallel combined diagnosis positive, and 132 serial combined diagnosis positive. Sensitivity of series combination diagnosis was significantly higher than other indexes (P < 0.05); especially, parallel combination diagnosis was significantly higher than other indexes (P < 0.05). Besides, area under the ROC curve of parallel combination diagnosis and series combination diagnosis was significantly higher than that of each index alone diagnosis (P < 0.05). Conclusion: In the diagnosis of chronic pulmonary heart disease, the combination of plasma BNP and HbAlc can effectively improve the diagnostic specificity and sensitivity, as well as improve the area under the ROC curve.

Comment to "Chronic disease management in heart failure: focus on telemedicine and remote monitoring".

No abstract present.

A multicenter program for electronic health record screening for patients with heart failure with preserved ejection fraction: Lessons from the DELIVER-EHR initiative.

Efficiency in clinical trial recruitment and enrollment remains a major challenge in many areas of clinical medicine. In particular, despite the prevalence of heart failure with preserved ejection fraction (HFpEF), identifying patients with HFpEF for clinical trials has proven to be especially challenging. In this manuscript, we review strategies for contemporary clinical trial recruitment and present insights from the results of the DELIVER Electronic Health Record (EHR) Screening Initiative. The DELIVER trial was designed to evaluate the effects of dapagliflozin on clinical outcomes in patients with HFpEF. Within this trial, the multicenter DELIVER EHR Screening Initiative utilized EHR-based techniques in order to improve recruitment at selected sites in the United States. For this initiative, we developed and deployed a computable phenotype from the trial's eligibility criteria along with additional EHR tools at interested sites. Sites were then surveyed at the end of the program regarding lessons learned. Six sites were recruited, trained, and supported to utilize the EHR methodology and computable phenotype. Sites found the initiative to be helpful in identifying eligible patients and cited the individualized expert technical support as a critical factor in utilizing the program effectively. We found that the major challenge of implementation was the process of converting traditional inclusion/exclusion criteria into a computable phenotype within an established and ongoing trial. Other significant challenges noted by sites were the following: impact of the COVID-19 pandemic, engagement/support by local institutions, and limited availability of internal EHR experts/resources to execute programming. The study represents a proof-of-concept in the ability to utilize EHR-based tools in clinical trial recruitment for patients with HFpEF and provides important lessons for future initiatives. ClinicalTrials.gov Identifier: NCT03619213.