Cohort Of Heart Failure Patients Research Articles

Real-world eligibility for GLP1-ra therapy in a cohort of heart failure patients

Abstract Background GLP1-ra have demonstrated substantial cardiovascular (CV) benefits in diabetic and, more recently, non-diabetic patients, however their use in heart failure (HF) patients is still limited. Purpose To evaluate real-word eligibility to GLP1-ra in a cohort of HF patients. Methods Demographic and clinical data from HF patients evaluated at a single center HF unit from August 1st 2021 to November 29th 2023 were automatically retrieved from the electronic health record (EHR). Patients were deemed eligible to GLP1-ra based on (1) absence of ongoing treatment with GLP1-ra and (2) either having type 2 diabetes mellitus (T2DM) or satisfying the inclusion criteria of the SELECT trial or those of the STEP-HFpEF trial, which were adapted according to the available information. A sensitivity analysis lowering the body mass-index cut-off to >= 27 kg/m2 also for the STEP-HFpEF trial was performed. Results 1754 patients with an established diagnosis of HF were included; median age was 78.3 (IQR 70.7-83.8) years and 697 patients were female (39.7%). 6 patients had type 1 diabetes mellitus. Among the remaining 1749 patients, 633 (36.2%) patients had T2DM and 14 were already treated with GLP1-ra. Among 1116 patients without diabetes, 302 (27.1%) were eligible to receive GLP1-ra according to the inclusion criteria of the SELECT or STEP-HFpEF trials. 226 (20.2%) satisfied the SELECT trial inclusion criteria and among them 100 (44.8%) had HF with reduced ejection fraction, whereas 136 patients (12.2%) were eligible to receive GLP1-ra according to the STEP-HFpEF trial. Changing the BMI cut-off to >= 27 kg/mq, as in the SELECT trial, 219 patients (19.6%) according to the STEP-HFpEF inclusion criteria and 344 (30.8%) overall were found to be eligible for GLP1-ra therapy. Conclusion Real-word eligibility to GLP1-ra may reach up to 55% of HF patients according to diabetes status or trial inclusion criteria.

Incidence of atrial fibrillation detected by an insertable cardiac monitor in a large real-world cohort of heart failure patients with reduced and preserved ejection fraction

Abstract Background Subcutaneous implantable cardiac monitors (ICM) have the capability to detect atrial fibrillation (AF) episodes with high degree of accuracy [1]. Objective We investigated the incidence of AF in patients implanted with an ICM and a clinical history of heart failure (HF) with reduced or preserved left ventricular ejection fraction (LVEF). Methods Patients with history of HF admissions who were implanted with an ICM were identified from the aggregated and de-identified electronic health record (EHR) database during 2007-2021. The device collected data were merged with the EHR data to create a de-identified database of real-world patients. Patients were included if they had ≥180 days of device follow-up. ICMs detect AF based on incoherence of RR intervals and absence of single p-wave between two R-waves [1]. All ICM detected AF episodes stored with at least 30 seconds of ECG at onset were adjudicated using an artificial intelligence (AI) model. The AI model was previously trained and validated using over 60K manually adjudicated episodes and was shown to have an accuracy of over 97% [2]. ICM detected AF episodes with AI model based true probability of AF ≥ 0.9 was analyzed. The Kaplan-Meier incidence curves for AF incidence as a function of episode duration, clinical history of AF, and LVEF are reported. Results A total of 1020 LINQ ICM patients with history of HF admission prior to implant were identified from the deidentified real-world dataset. LVEF was available in 889 (87%) patients, of whom 394 (44%) had EF <50%, and 495 (56%) had EF≥50%. NYHA class was available in 296 (29%) patients, of whom 39 (13%) were class I, 126 (43%) were class II, 112 (38%) were class III, and 19 (6%) were class IV. Patients had an average age of 68±13 years with 52% being males and had clinical history of hypertension in 95%, diabetes in 56%, coronary artery disease in 75%, AF in 57%, stroke/TIA in 51%, and renal dysfunction in 53%. A total of 911 patients with ≥180 days of follow-up (average follow-up of 25.8 months) were included. A total of 8407 episodes from 358 patients were classified by the AI model as true AF. The incidence of AF as a function of episode duration, clinical history of AF and reduced vs preserved LVEF are shown in Figures A, B, and C respectively. Incidence of AF, as detected by an ICM over 42 months of follow-up, was estimated to be 38% to 46% depending on AF episode duration. Estimated 42-month AF incidence was 23% in patients with no clinical history of AF. The 42-month AF incidence was 44% vs 47% in HF patients with reduced versus preserved LVEF. Conclusion Incidence of AF, as detected by an ICM over 3 years of follow-up, was estimated to be in close to half of ICM patients with history of HF events. Close to one fourth of the patients with no prior clinical history of AF had newly detected AF. AF incidence was similar in HF patients with preserved versus reduced LVEF in this real-world cohort.

Comparative analysis of clinical outcomes in patients undergoing primary CRT implantation versus CRT upgrade: single center experience

Abstract Background As heart failure (HF) management evolves, cardiac resynchronization therapy (CRT) has emerged as a cornerstone intervention, improving left ventricular (LV) function and reducing morbidity and mortality. The Budapest trial specifically addressed upgrading from permanent pacemaker (PPM) to CRT, emphasizing the potential for improved clinical outcomes and quality of life in this population. The findings highlighted the impact of CRT upgrade and contribute valuable insights to the cardiac device strategies for HF patients. This study aims to compare clinical outcomes between patients undergoing primary CRT implantation and those undergoing CRT upgrade. Methods A retrospective analysis was conducted on a cohort of heart failure patients who received CRT devices between 2015 and 2019. Patients were categorized into two groups: those undergoing primary CRT implantation and those undergoing CRT upgrade. Clinical outcomes, including mortality rate, hospitalization for HF exacerbation, and improvements in left ventricular ejection fraction (LVEF), were assessed and compared between the two groups. Results A total of 847 patients were included in the study, with 74,5% (n=631) undergoing primary CRT implantation and 13,5% (n=114) receiving CRT upgrades. The mean age was 72±10 years-old and 57% (n=485) were women, and a mean follow-up time of 23±8 months. 33.7% (n=285) of the total were of ischemic etiology. The primary CRT implantation group demonstrated a mortality of 34% (n=215) and 13% (n=84) of hospitalization due to HF; NYHA functional class improvement in 58% (n=369), and 35,7% (n=225) were CRT responders with a mean LV ejection fraction (EF) improvement of ±10%, while the CRT upgrade group had a 31% (n=36) mortality and 19% (n=22) of hospitalization due to HF; NYHA functional class improvement in 60% (n=68), and 27% (n=31) were CRT responders with a mean LV EF improvement of 8,7%. There were no statistically significant differences regarding each endpoint, namely mortality, HF hospitalizations, NYHA functional class improvement, CRT responders and mean LVEF improvement. Conclusion A clear benefit from implantation of a primary CRT device implantation has already been demonstrated. However, recent trials revealed there was also benefit in upgrading from PPM to CRT patients with decrease LVEF, comparing with PPM. This study showed that the benefits from primary CRT were similar to the benefits from upgrading CRT, in terms of mortality reduction, HF hospitalizations, NYHA functional class improvement, CRT responders and mean LVEF improvement. Once again, just like in the most recent trials, this study demonstrates the clear benefit of upgrading from a PPM to CRT in patients with decreased LVEF.

Interventional rhythm control is associated with an improved long-term prognosis of patients with atrial fibrillation undergoing transcatheter edge-to-edge mitral valve repair

Abstract Background Atrial fibrillation (AF) is the most common concomitant disease in patients undergoing transcatheter edge-to-edge repair (TEER) for severe mitral regurgitation (MR) and detrimentally affects their long-term survival. While the prognostic improvement of catheter ablation (CA) of AF in the overall cohort of heart failure (HF) patients as well as that of surgical ablation of AF with concomitant MR surgery are well established, data on the outcomes of CA of AF in TEER patients are lacking. Methods In a multicenter retrospective observational cohort study, consecutive patients undergoing TEER were enrolled and long-term survival of patients receiving catheter ablation (CA) for AF was compared with that of patients on pharmacological AF treatment and with that of patients without a history of AF, using propensity score matching and multivariable Cox regression analyses. Results A total of 821 patients were identified who successfully underwent TEER procedure. Within this cohort, 608 (74.1%) had concomitant AF, of which 48 patients received CA. Patients with CA of AF showed significantly higher cumulative survival 5 years after the TEER procedure compared with propensity score-matched patients on pharmacological rhythm control of AF (64.6% [31/48] vs. 33.3% [64/192], p=0.01) or on rate control of AF (64.6% [31/48] vs. 25.0% [24/96], p=0.0015). Multivariable Cox regression analysis confirmed that CA of AF was independently associated with significantly better long-term outcome than pharmacological rhythm control and rate control of AF (hazard ratio [HR] 0.4, 95%-confidence interval [CI] 0.2-0.9, p=0.02 and HR 0.4, 95%-CI 0.2-0.7, p=0.004, respectively). CA even offsets the prognostic disadvantage of coexisting AF, as the cumulative survival 5 years after TEER intervention is not significantly different from propensity score-matched TEER patients without a history of AF (64.6% [31/48] vs. 38.9% [56/144], p=0.3). Conclusion Using established statistical methods of propensity score matching and multivariable Cox regression, we demonstrate a significantly improved long-term outcome of TEER patients undergoing CA of concomitant AF compared with pharmacological AF management. CA even offsets the prognostic disadvantage of coexisting AF, as the outcome is not significantly different from that of TEER patients without a history of AF. In light of the growing evidence of prognostic benefit and safety of CA of AF in the overall cohort of HF patients, our data, albeit not randomized, provide strong evidence for interventional rhythm control of AF as an essential part of a modern and holistic management of TEER patients. We alert to the importance of treating concomitant AF, as this is a very promising approach to improve the prognosis of this unique and continually growing HF population.Flow chart of the study designSurvival analyses of PSM cohorts

Catheter ablation of concomitant atrial fibrillation improves survival of patients undergoing transcatheter edge-to-edge mitral valve repair.

Atrial fibrillation (AF) is the most common concomitant disease in patients undergoing transcatheter edge-to-edge repair (TEER) for mitral regurgitation (MR) and detrimentally affects their outcome. While there is increasing evidence for prognostic improvement and safety of catheter ablation (CA) of AF in the overall cohort of heart failure patients, corresponding data in TEER patients are lacking. To investigate the impact of treatment regimens for concomitant AF on survival of TEER patients. In a multicenter observational cohort study consecutive patients successfully undergoing TEER were analyzed and survival of patients receiving CA of concomitant AF was compared with that of patients on pharmacological AF treatment and with that of patients without a history of AF, using propensity score matching (PSM). A total of 821 patients were analyzed. Of these, 608 (74.1%) had concomitant AF, of whom 48 patients received CA. Patients with CA in AF showed significantly higher 3-year-survival after TEER compared to PSM-patients on pharmacological AF treatment (75.5% [36/48] vs. 49.4% [166/336], p = 0.009). The 3-year-survival after TEER of patients with concomitant AF treated with CA was not significantly different from PSM-patients without AF (75.5% [36/48] vs. 68.3% [98/144], p = 0.36). CA of AF is superior to pharmacotherapy as it significantly improves the survival of TEER patients in a PSM analysis. CA even offsets the prognostic disadvantage of coexisting AF in TEER patients. Given the growing evidence of prognostic benefits in the overall cohort of HF patients, our data point out the importance of treating concomitant AF and support CA as an essential part of a holistic management of TEER patients.

Short-term outcomes after sodium-glucose cotransporter-2 inhibitor initiation in a cohort of heart failure patients.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) decrease mortality and risk of hospitalization in patients with heart failure with reduced ejection fraction (HFrEF). SGLT2i have a natriuretic effect shortly after initiation, followed by a lasting osmotic diuretic effect. We sought to evaluate rates of acute kidney injury (AKI) and therapy discontinuation with SGLT2i initiation in a real-world cohort of HFrEF patients. We abstracted data on 200 patients with HFrEF initiated on a SGLT2i in the outpatient setting at the University of Michigan (between 1 July 2016 and 2 July 2022). Our co-primary endpoints were rate of AKI and discontinuation of SGLT2i. A total of 200 patients were included. The majority of patients were male (64%) with a mean left ventricular ejection fraction (LVEF) of 27%. One hundred and four (52%) patients had diabetes mellitus. Most patients exhibited New York Heart Association class II (51.5%) or III (33.5%) symptoms. The majority of patients (54%) were taking an angiotensin-receptor neprilysin inhibitor. The mean daily furosemide equivalent diuretic dose was 93.3mg. AKI occurred in 22 patients and 18 patients discontinued their SGLT2i. Yeast infection (n=6), hypotension (n=5), and AKI (n=4) were the most common reasons for discontinuation. Using receiver operating characteristic curve analysis, the strongest models for AKI were A1C [area underneath its curve (AUC)=75.8, empirical confidence interval (ECI) 66.5-83.5]; baseline serum creatinine (SCr) (AUC=72.0, ECI 65.7-78.7); LVEF (AUC=67.6, ECI 58.4-75.8); and furosemide equivalent diuretic dose (AUC=66.0, ECI 57.5-74.6). Similarly, the strongest positive models for SGLT2i discontinuation were A1C (AUC=81.1, ECI 74.8-87.2); baseline SCr (AUC=67.4, ECI 58.7-75.5); LVEF (AUC=68.7, ECI 58.9-76.5); and furosemide equivalent diuretic dose (AUC=67.2, ECI 58.2-76.0). A1C was the strongest model of AKI, and SGLT2i discontinuation in HFrEF patients started on SGLT2i. Glucosuria may be related to this effect. Patients with higher baseline SCr on higher doses of loop diuretics may be at greater risk of these outcomes. Future prospective studies will be needed to further evaluate these findings and other models of AKI and SGLT2i discontinuation to guide clinical use of SGLT2 inhibitors.

Exercise Oscillatory Ventilation Improves Heart Failure Prognostic Scores.

Several heart failure (HF) prognostic risk scores are available to guide the ideal time for listing candidates for a heart transplant (HTx). The detection of exercise oscillatory ventilation (EOV) during cardiopulmonary exercise testing (CPET) is associated with advanced HF and a worse prognosis, and yet it is not accounted for in these risk scores. Therefore, this study aimed to assess whether EOV further adds prognostic value to HF scores. A single-centre retrospective cohort study was undertaken of consecutive HF patients with reduced ejection fraction (HFrEF) who underwent CPET from 1996 to 2018. The Heart Failure Survival Score (HFSS), Seattle Heart Failure Model (SHFM), Meta-analysis Global Group In Chronic Heart Failure (MAGGIC), and Metabolic Exercise Cardiac Kidney Index (MECKI) were calculated. The added value of EOV on top of those scores was assessed using a Cox proportional hazard model. The added discriminative power was also assessed by receiver operating characteristic curve comparison. A total of 390 HF patients with a median age of 58 (IQR 50-65) years were investigated, of whom 78% were male and 54% had ischaemic heart disease. The median peak oxygen consumption was 15.7 mL/kg/min (IQR 12.8-20.1). Exercise oscillatory ventilation was detected in 153 (39.2%) patients. Over a median follow-up of 2 years, 61 patients died (49 due to a cardiovascular reason) and 54 had a HTx. Exercise oscillatory ventilation independently predicted the composite outcome of all-cause death and HTx. Furthermore, the presence of this ventilatory pattern significantly improved the prognostic performance of both HFSS and MAGGIC scores. Exercise oscillatory ventilation was often found in a cohort of HF patients with reduced LVEF who underwent CPET. It was found that EOV added further prognostic value to contemporary HF scores, suggesting that this easily obtained parameter should be included in future modified HF scores.

A network medicine approach to study comorbidities in heart failure with preserved ejection fraction

BackgroundComorbidities are expected to impact the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). However, comorbidity profiles are usually reduced to a few comorbid disorders. Systems medicine approaches can model phenome-wide comorbidity profiles to improve our understanding of HFpEF and infer associated genetic profiles.MethodsWe retrospectively explored 569 comorbidities in 29,047 HF patients, including 8062 HFpEF and 6585 HF with reduced ejection fraction (HFrEF) patients from a German university hospital. We assessed differences in comorbidity profiles between HF subtypes via multiple correspondence analysis. Then, we used machine learning classifiers to identify distinctive comorbidity profiles of HFpEF and HFrEF patients. Moreover, we built a comorbidity network (HFnet) to identify the main disease clusters that summarized the phenome-wide comorbidity. Lastly, we predicted novel gene candidates for HFpEF by linking the HFnet to a multilayer gene network, integrating multiple databases. To corroborate HFpEF candidate genes, we collected transcriptomic data in a murine HFpEF model. We compared predicted genes with the murine disease signature as well as with the literature.ResultsWe found a high degree of variance between the comorbidity profiles of HFpEF and HFrEF, while each was more similar to HFmrEF. The comorbidities present in HFpEF patients were more diverse than those in HFrEF and included neoplastic, osteologic and rheumatoid disorders. Disease communities in the HFnet captured important comorbidity concepts of HF patients which could be assigned to HF subtypes, age groups, and sex. Based on the HFpEF comorbidity profile, we predicted and recovered gene candidates, including genes involved in fibrosis (COL3A1, LOX, SMAD9, PTHL), hypertrophy (GATA5, MYH7), oxidative stress (NOS1, GSST1, XDH), and endoplasmic reticulum stress (ATF6). Finally, predicted genes were significantly overrepresented in the murine transcriptomic disease signature providing additional plausibility for their relevance.ConclusionsWe applied systems medicine concepts to analyze comorbidity profiles in a HF patient cohort. We were able to identify disease clusters that helped to characterize HF patients. We derived a distinct comorbidity profile for HFpEF, which was leveraged to suggest novel candidate genes via network propagation. The identification of distinctive comorbidity profiles and candidate genes from routine clinical data provides insights that may be leveraged to improve diagnosis and identify treatment targets for HFpEF patients.Graphical

CE-452776-1 EARLY INITIATION OF ARNI AND SGLT2I IS ASSOCIATED WITH DELAYED ATRIAL FIBRILLATION IN HEART FAILURE PATIENTS

Early use of mineralocorticoid receptor antagonists (MRA), sodium-glucose co-transporter inhibitors (SGLT2i) and angiotensin receptor-neprilysin inhibitors (ARNI) have shown benefit in major trials for heart failure patients and in other studies for recurrence of atrial fibrillation (AF) after ablation. Whether these medications and their resulting improved remodeling are associated with delayed onset of AF in a real-world heart failure cohort is unknown. We aimed to define the clinical phenotype of heart failure patients receiving early use (within 6 months) of MRA, SGLT2i, and ARNIs. We also investigated the association between use of these medications and time to first hospitalization with AF. We analyzed the electronic health records of the University of Pittsburgh Medical Center, a large multi-hospital system, between 2010 and 2022. Differences between baseline demographics, cardiovascular risk factors, and comorbidity burden were evaluated with t tests. Adjusted Cox proportional hazards models were performed to evaluate the association between early use of the medications and onset of AF for all heart failure patients and subgroups with reduced (HFrEF) and preserved (HFpEF) ejection fractions. Among 57689 patients, 2834 (5%) developed AF in the follow up period (median 3.3 years, IQR 4.7). A total 12015 (21%) had early initiation of MRA, 2259 (4%) SGLT2i, and 2909 (5%) ARNI. Patients receiving these medications were significantly more male with more commercial insurance, initial evaluation by cardiologists, and lower CHA2DS2VASC and Elixhauser comorbidity scores (table 1). In multivariate Cox models, delayed onset of AF hospitalization was associated with both use of early SGLT2i (HR 0.56, 95% CI 0.39-0.80, p<0.01) and ARNI (HR 0.52, 95% CI 0.39-0.70, p<0.001) but not MRA (figure 1). This trend was echoed in HFrEF patients (SGLT2i HR 0.46, 95% CI 0.24-0.89, p<0.05; ARNI HR 0.59, 95% CI 0.42-0.84, p<0.01) but associations were not significant in HFpEF. In a large, real-world cohort of heart failure patients, early use of ARNI and SGLT2i is significantly associated with delayed onset of AF. This association was driven largely by the HFrEF cohort. While only 5% of patients developed AF, early use of ARNI and SGLT2i in all indicated heart failure patients may decrease AF onset and morbidity in an already high-risk population.Tabled 1Table 1: Selected Baseline Characteristics of All Heart Failure Patients Receiving Early MRA, SGLT2i, and ARNI TherapyEarly Use of MRA-YESEarly Use of MRA-NOEarly Use of SGLT2i-YESEarly Use of SGLT2i-NOEarly Use of ARNI-YESEarly Use of ARNI-NOAge (mean±SD)67±14.172±13.865±12.671±14.065±13.571±14.0Male Sex (%)545061506550White Race (%)858987878488Commercial Insurance (%)242226222922Initial Evaluation by a Cardiologist (%)483947435540CHA2DS2VASC score (mean±SD)3.7±1.64.1±1.54.0±1.64.0±1.53.5±1.64.0±1.6Mean Elixhauser comorbidity score10.4119.210.91010.9Prior coronary revascularization (%)423346354735Confirmed HFrEF (%)301433165215Confirmed HFpEF (%)17231522423Early use of MRA (%)NANA48205619Early use of SGLT2i (%)93NANA273Early use of ARNI (%)14-NS3-NS35-NS4-NSNANANote: All pairs noted above are significant with p<0.01 except for those labeled "-NS", which are not significant. Open table in a new tab

Abstract P180: Disparities in Occurrence of Stroke Among Heart Failure Patients- A Case Control Study Evaluating Impact of Community Socioeconomic Distress Index

Introduction: Ischemic stroke is common complication among heart failure patients. Community-level socio-economic distress has been linked to adverse clinical outcomes in prior research. However, few to no studies have examined the relationship between neighborhood level socio-economic distress and stroke within a population of heart failure patients exclusively. Hypothesis: Odds of stroke among patients with heart failure are higher in neighborhoods with increased socio-economic distress, controlling for patient demographic and clinical comorbidities. Methods: Two separate cohorts of heart failure patients were assembled using ICD9/10 codes to identify all patients with a heart failure diagnosis seen at West Virginia University Hospital Systems (WVU Medicine) between 2008 and 2020 and Charleston Area Medical Center (CAMC) between 2017 and 2020. Cases were defined as heart failure patients with a diagnosis of ischemic stroke. Controls were defined as heart failure patients without a diagnosis of stroke and were matched to cases 4:1 on five-year age grouping and sex at birth. Distressed communities index (DCI) was linked to clinical data by patient zip code of residence. Neighborhoods with a DCI above 75 were classified as distressed, while those below were noted as non-distressed. Multivariable conditional logistic regression was used to identify significant associations at the 95% confidence level within each cohort separately. Results: In total there were 26,532 unique heart failure patients in the WVU Medicine cohort and 20,070 in the CAMC cohort. Of these, 10.3% (n=2,741) of the WVU Medicine cohort and 4.5% (n=900) of the CAMC cohort met the case definition of having had a diagnosis of stroke. Among patients in the WVU Medicine cohort with heart failure who experienced a stroke, 47.1% (n=1,291) were male and had an average age of 72.4 (± 12.9). In the CAMC cohort, among heart failure patients who experienced a stroke, 51.1% (n=460) were male and the average age was 70.9 (± 11.8). After controlling for demographics and clinical comorbidities, conditional logistic regression analyses identified a statistically significant association between neighborhood-level socio-economic distress in both the WVU Medicine cohort (OR = 1.31; 95% CI = 1.20 - 1.44) and the CAMC cohort (OR = 1.29; 95% CI = 1.027 - 1.454). Conclusion: Neighborhood-level socio-economic distress was associated with prevalence of stroke among heart failure patients. This is a critical finding for rural states, such as West Virginia, as it has the ability to inform placement of new satellite clinics among large hospital systems, or government funded clinics, such as federally qualified health centers, to address inequities in care for patients living in medically underserved communities.

Challenges of Sodium-glucose Transporter-2 Inhibitors Use in a low Socioeconomic Setting

Background: Sodium-glucose transporter-2 (SGLT2) inhibitors have shown efficacy in reducing major adverse cardiovascular events and hospitalizations for heart failure in patients with type 2 diabetes mellitus and concomitant heart failure. Aim: To compare the short-term effectiveness between empagliflozin and dapagliflozin. Methods: A single-center observational cohort study was implemented in a Dominican tertiary-care center, where patients with heart failure and reduced ejection fraction were divided into two groups and treated with different SGLT2 inhibitor molecules, empagliflozin and dapagliflozin. Two-step cluster analysis was conducted for the interim analysis of the study. Results: We enrolled a total of 60 patients, with a median age of 69. The majority of these were men (70%) and comprised 75.0% of the Dapagliflozin 10 mg group and 62.5% of the Empagliflozin 10 mg group. Most participants (61.7%) were categorized as NYHA-II in functional class. The main cause of heart failure was ischemic (55%), while the predominant state of the disease was chronic with 65% patients in this group. Conclusion: This preliminary manuscript evaluated the effectiveness of SGLT2 inhibitors in a Dominican heart failure patient cohort, finding notable gender, age, and risk factor variations, and emphasizing the need for standardized research methods in future investigations.

The Role of Daily Implant-Based Multiparametric Telemonitoring in Patients with a Ventricular Assist Device.

The telemonitoring of heart failure (HF) patients is becoming increasingly important. This study aimed to evaluate the benefit of telemonitoring in end-stage HF patients with a ventricular-assistance device (VAD). A total of 26 HF-patients (66 ± 11 years, 88% male) on VAD therapy with an implantable cardioverter-defibrillator (ICD) or a cardiac resynchronization defibrillator (CRT-D) including telemonitoring function were enrolled. The long-term follow-up data (4.10 ± 2.58 years) were assessed. All the patients (n = 26, 100%) received daily ICD/CRT-D telemonitoring. In most of the patients (73%, n = 19), the telemedical center had to take action for a mean of three times. An acute alert due to sustained ventricular arrhythmias (VAs) occurred in 12 patients (63%) with 50% of them (n = 6) requiring ICD shock delivery. Eight patients (67%) were hospitalized due to symptomatic VAs. In 11 patients (92%), immediate medication adjustments were recommended. Relevant lead issues were revealed in thirteen patients (50%), with six patients (46%) undergoing consecutive lead revisions. Most of the events (83%) were detected within 24 h. Daily telemonitoring significantly reduced the number of in-hospital device controls by 44% (p &lt; 0.01). The telemonitoring ensured that cardiac arrhythmias and device/lead problems were identified early, allowing pre-emptive and prompt interventions. In addition, the telemonitoring significantly reduced the number of in-hospital device controls in this cohort of HF patients.

1111 INTACT FIBROBLAST GROWTH FACTOR 23 TESTED BY A FULLY AUTOMATED ASSAY: CLINICAL CORRELATES AND PROGNOSTIC VALUE IN CHRONIC SYSTOLIC HEART FAILURE

Abstract Background and aims Fibroblast growth factor-23 (FGF23) has been associated with left ventricular (LV) hypertrophy, fibrosis, and heart failure (HF). We aimed to investigate the clinical correlates and prognostic value of intact FGF23 (iFGF23) in HF patients. Methods Patients with systolic HF (left ventricular ejection fraction – LVEF &amp;lt;50%) were prospectively enrolled. iFGF23 was tested with a fully automated immuno-chemiluminescent assay. Patients were divided into iFGF23 tertiles and followed-up for all-cause death, cardiac death, and the composite of all-cause death and HF hospitalizations. Results We enrolled 150 patients (82% males; median age 65 years). First, second, and third iFGF23 tertiles were &amp;lt;35.2 pg/mL, 35.2-50.9 pg/mL, and &amp;gt;50.9 pg/mL. Patients in the upper iFGF23 tertile had lower LVEF (p=0.014), higher N-terminal pro-B-type natriuretic peptide (NT-proBNP, p=0.001), and lower peak VO2 (p&amp;lt;0.001). Plasma phosphate, estimated glomerular filtration rate (eGFR), and LV mass index were independently associated with higher iFGF23 levels (all p&amp;lt;0.05). Patients in the upper tertile were at higher risk of all-cause death (p=0.001), cardiac death (p=0.001), and of the composite of all-cause death and HF hospitalizations (p=0.003). iFGF-23 was an independent predictor of all the endpoints after adjustment for age, LVEF, eGFR, and NT-proBNP. Conclusions Circulating iFGF23 is associated with renal dysfunction, disease severity and outcome in systolic HF. Figure. Prognostic impact of FGF23 levels in patients with systolic heart failure (HF). In a cohort of HF patients with systolic dysfunction, higher iFGF23 levels (marker of increased cardiac fibrosis and hypertrophy) were associated with a more severe disease, as expressed by lower left ventricular systolic function, higher circulating levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), lower oxygen consumption at cardiopulmonary exercise test and worse renal function. Moreover, iFGF23 elevation identified patients at higher risk for all-cause and cardiac mortality, and HF hospitalization.

Abstract 10390: Using a Trial Modelling Framework to Emulate a Target Trial Evaluating Revascularisation Strategies in Patients With Heart Failure

Introduction: We developed a novel trial modelling framework which utilises real world data to emulate a target trial and estimate key parameters to support trial planning. We applied this framework using the UK Hospital Episode Statistics (HES), which captures all admissions at NHS hospitals in England, and reported the findings of an emulated target trial evaluating revascularisation strategies in heart failure (HF) patients with coronary artery disease. Methods: Phenotyping algorithms derived from the target trial protocol were applied to HES, to identify HF patients who had coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA). Trial participants are often different from the target trial population due to voluntary basis of participation. The HES-derived cohort was matched on baseline features (age, gender, comorbidities) to an existing trial (STICH) which targeted the same high-risk population, so that the matched cohort mimics a likely trial population. Treatment effects were estimated using instrumental variable analysis (IVA) and meta-learning models to adjust for confounding. Results: A total of 13,519 HF patients undergoing revascularisation during April 2009 and March 2015 met the eligibility criteria. This HF patient cohort was matched with the STICH cohort, resulting in 2046 patients in the study cohort. The 5-year composite outcome of all-cause mortality or cardiovascular hospitalisation was observed in 51.1% of HF patients who had CABG and 70.0% in those who had PTCA. IVA showed that CABG was associated with a lower risk of the composite outcome (risk difference -16.2%, 95%CI: -20.6% to -11.8%). This was consistent with the treatment effects derived from other machine learning models. Our analyses also identified a trend in greater treatment effects being observed in the matched cohort than unmatched cohort. This suggests that a clinical trial may over-estimate treatment effects when compared to the actual treatment benefit observed in clinical practice. Conclusions: The framework provides a structured process to emulate a trial and anticipate findings of the trial. Our analyses showed that CABG is associated with a greater long-term benefit in HF patients requiring revascularisation.

Acute Decompensated Heart Failure in Patients With and Without COVID-19 — The Experience of a Romanian Center

Abstract Objective Our goal was to characterize a cohort of heart failure patients with and without COVID-19 in terms of demographics, comorbid conditions, treatment regimens, lab test results and outcome. Methods We performed a retrospective, unicentric, cohort study on consecutive patients admitted to our department between September and December 2021. Results We enrolled a total of 76 HF patients – 65.3% COVID-19 (+). The median age was 72 years with a female predominance (59.2%). The median length of hospitalization was 13 days, longer for COVID-19 (+). Only 20.7% of all patients were fully vaccinated. COVID-19 (+) patients had higher ICU admission rates and mortality (in-hospital and at follow-up). The most common associated conditions were HTN (78.9%), T2DM (38.2%), cancer (18.4%), CAD (17.1%), late-stage CKD (16.7%), AF (14.5%) and stroke (11.8%). Patients with a history of stroke were more likely to require ICU management. At-home treatment with ACEi/ARB/ARNi made no difference for COVID-19 severity (p = 0.393), mechanical ventilation (p = 0.101) or mortality (in-hospital: p = 0.316; follow-up: p = 0.563); however, ICU admission rates were lower in these patients (p = 0.023). Conclusion Heart failure with preserved ejection fraction and low symptom severity were common findings among COVID-19 positive patients. However, COVID-19 positive patients were hospitalized for longer, required more ICU care and had higher mortality both in-hospital and at follow-up.

Risks and benefits of urinary catheterisation during inpatient diuretic therapy for acute heart failure: a retrospective, non-inferiority, cohort study

ObjectivesPatients with acute congestive heart failure (HF) regularly undergo urinary catheterisation (UC) at hospital admission. We hypothesised that UC has no clinical benefits with regard to weight loss during inpatient...

Sphingomyelinase activity promotes atrophy and attenuates force in human muscle fibres and is elevated in heart failure patients.

BackgroundActivation of sphingomyelinase (SMase) as a result of a general inflammatory response has been implicated as a mechanism underlying disease‐related loss of skeletal muscle mass and function in several clinical conditions including heart failure. Here, for the first time, we characterize the effects of SMase activity on human muscle fibre contractile function and assess skeletal muscle SMase activity in heart failure patients.MethodsThe effects of SMase on force production and intracellular Ca2+ handling were investigated in single intact human muscle fibres. Additional mechanistic studies were performed in single mouse toe muscle fibres. RNA sequencing was performed in human muscle bundles exposed to SMase. Intramuscular SMase activity was measured from heart failure patients (n = 61, age 69 ± 0.8 years, NYHA III‐IV, ejection fraction 25 ± 1.0%, peak VO2 14.4 ± 0.6 mL × kg × min) and healthy age‐matched control subjects (n = 10, age 71 ± 2.2 years, ejection fraction 60 ± 1.2%, peak VO2 25.8 ± 1.1 mL × kg × min). SMase activity was related to circulatory factors known to be associated with progression and disease severity in heart failure.ResultsSphingomyelinase reduced muscle fibre force production (−30%, P < 0.05) by impairing sarcoplasmic reticulum (SR) Ca2+ release (P < 0.05) and reducing myofibrillar Ca2+ sensitivity. In human muscle bundles exposed to SMase, RNA sequencing analysis revealed 180 and 291 genes as up‐regulated and down‐regulated, respectively, at a FDR of 1%. Gene‐set enrichment analysis identified ‘proteasome degradation’ as an up‐regulated pathway (average fold‐change 1.1, P = 0.008), while the pathway ‘cytoplasmic ribosomal proteins’ (average fold‐change 0.8, P < 0.0001) and factors involving proliferation of muscle cells (average fold‐change 0.8, P = 0.0002) where identified as down‐regulated. Intramuscular SMase activity was ~20% higher (P < 0.05) in human heart failure patients than in age‐matched healthy controls and was positively correlated with markers of disease severity and progression, and with several circulating inflammatory proteins, including TNF‐receptor 1 and 2. In a longitudinal cohort of heart failure patients (n = 6, mean follow‐up time 2.5 ± 0.2 years), SMase activity was demonstrated to increase by 30% (P < 0.05) with duration of disease.ConclusionsThe present findings implicate activation of skeletal muscle SMase as a mechanism underlying human heart failure‐related loss of muscle mass and function. Moreover, our findings strengthen the idea that SMase activation may underpin disease‐related loss of muscle mass and function in other clinical conditions, acting as a common patophysiological mechanism for the myopathy often reported in diseases associated with a systemic inflammatory response.

Our Continued Experience With Using Watchpat® (itamar Medical, Ltd.), Home Sleep Testing For The Diagnosis Of Sleep Apnea In Heart Failure And Orthotopic Heart Transplant Patients.

<h3>Introduction</h3> Untreated sleep disorders are well known to significantly increase risk of coronary artery disease (CAD), hypertension (HTN), obesity, diabetes (DM), anxiety and depression. Despite maximal medical therapy, approximately 50% of patients with heart failure (HF) have moderate-to-severe sleep apnea (SA). Moreover, obstructive sleep apnea (OSA) has also been described in cardiac transplant recipients (OHT) as a significant risk factor for late graft dysfunction, thus screening and diagnosis is critical^. Access to in-lab polysomnography (PSG) has been limited throughout the pandemic leading to more reliance on home sleep testing. WatchPAT® Home Sleep Testing (WPHST) has been validated to accurately detect both obstructive as well as central sleep apnea (CSA) in the general population yet there is limited data to date that support its use in advanced HF/OHT patients. <h3>Objective</h3> Herein we describe our prospective utilization of WPHST highlighting differences in sleep apnea patterns in our HF and OHT population. <h3>Methods</h3> This is a single center, prospective, observational analysis, beginning February 22, 2020 through April 7, 2021. 50 consecutive patients that screened positive on the STOP-BANG® sleep apnea screen questionnaire were consented and assigned to WPHST and analyzed for comorbidities, and SA patterns and severity. <h3>Results</h3> Of the 50 patients enrolled, 48 patients (n=38 HF and n=10 OHT) were included in the analysis (1 failed study in each arm). Baseline characteristics were equivalent; mean age of 60 years, BMI 28.6 kg/m2, and 75% were male. A high prevalence of co-morbid conditions included CAD 52%, DM 50% and HTN 98%, (fig 1). Central/Mixed Sleep apnea accounted for 10.4% of the total cohort. Apnea Hypopnea Index (AHI) was significantly greater in the HF patient cohort vs OHT (p=0.02). However, no statistical differences were noted in nocturnal 02 sat (p=0.49). REM% was lower in the OHT compared to the HF cohort (p=0.049). <h3>Conclusion</h3> : In this limited prospective study AHI was significantly higher in the HF cohort compared to OHT. More importantly, WPHST has contributed to greater access to sleep diagnostics for high-risk patient populations throughout the pandemic. Continued work on short- and long-term outcomes is warranted.

The GENICA project - a prospective cohort of heart failure patients with a comprehensive ambulatory approach aiming better outcomes: study protocol.

Heart failure (HF) is a syndrome increasing worldwide, and literature shows that the hospitalizations are associated with greater mortality rates. A patient-centered method combined with optimized medical treatment and palliative care may improve HF outcomes, and some advocate a multifaceted approach to achieve a perfect management of chronic HF (CHF). The objective of this study was to present the study protocol of GENICA project which aims to optimize the ambulatory approach of CHF patients, and reduce their re-hospitalization, emergency readmission, and global death rate. Prospective cohort including patients referred to HF consultation and collecting sociodemographic, clinical, and analytical variables among others. The outcomes will be mortality, re-hospitalization, and emergency readmission rates. The association between the independent variables and outcomes will be assessed by logistic regression. Comparison between GENICA patients and controls will be made by χ2 test. Significance at p level of less than 0.05. GENICA will offer a wide range of longitudinal data with evidence that will influence future healthcare of CHF patients at an ambulatory basis. GENICA will provide practical evidence of real HF patient's profile and develop workable decision algorithms, which will influence future ambulatory care of CHF. HF patients will be safer at home and will keep stability for longer periods, consuming less health resources and slow the progression of the disease. Being a matched cohort, GENICA benefits from an accuracy similar to that of randomized controlled trials, without the need to perform a rigorous allocation of the intervention. Being prospective there's no problem about response bias. CHF should be approached with a multidisciplinary and multifaceted strategy privileging the outpatient setting, including home monitoring, and GENICA is the paramount protocol enabling this. GENICA may come to show health policy makers that the asset is not to divide and rule, but to converge strategies, therapies, and knowledge.

Obesity and Uncontrolled Diabetes Predict Depression in HF Patients.

Background and aim: Heart failure (HF) is a clinical syndrome associated with poor quality of life and prognosis, and premature mortality. The aim of this study was to assess the prevalence of depression and its risk factors in HF patients. Methods: The study included 151 HF patients (mean age of 66.6 ± 11 years, 52.3% female). Based on ejection fraction (EF), the study cohort was divided into the following two groups: group-I: HFpEF patients (EF ≥ 50%, n = 47) and group-II: HFrEF patients (EF < 40%, n = 104). For the enrolled patients, demographic, clinic and echocardiographic indices, and depression scale results were collected. Results: The patients with HF and depression were older, mostly females, more obese, and had a higher glycemic level and higher NYHA functional class compared with the patients without depression (p < 0.05 for all). The left ventricle (LV) and left atrial (LA) dimensions were larger, and EF was lower, in patients with depression compared to those without depression (p < 0.05 for all), while the right ventricle (RV) measurements did not differ (p > 0.05). The same parameters remained significantly different when the patients were divided into HFpEF and HFrEF. The depression scale correlated with glycemic level (r = 0.51, p = 0.01), obesity (rpb = 0.53, p = 0.001), age (r = 0.47, p = 0.02), and severity of NYHA class (rpb = 0.54, p = 0.001). On a multivariate model, BMI ≥ 30 kg/m2, OR 1.890 (1.199 to 3.551; 0.02) glycemic level ≥ 8.5 mmol/L, OR 2.802 (1.709 to 5.077; p = 0.01), and NYHA class > 2, OR 2.103 (1.389 to 4.700; p = 0.01), proved to be the most powerful independent predictors of depression, in the group as a whole. Obesity and uncontrolled diabetes predicted depression, irrespective of EF. Conclusions: In this modest cohort of HF patients, obesity and uncontrolled diabetes were independent predictors of depression, irrespective of LV systolic function. This emphasizes the important role of medical education for better control of such risk factors.