Reduce Heart Failure Hospitalization Research Articles

Levosimendan in outpatients with advanced heart failure: Single-center experience of 200 intermittent perfusions

IntroductionPatients with advanced heart failure (HF) have high morbidity and mortality, with only a small proportion being eligible for advanced therapies. Intermittent outpatient levosimendan infusion has been shown to provide symptomatic relief and reduce the rate of HF events. Our aim was to assess the safety and efficacy of outpatient levosimendan administration in an advanced HF population. MethodsThis is a report of a single-center experience of consecutive advanced HF patients referred for intermittent intravenous outpatient administration of levosimendan, between January 2018 and March 2021. Baseline and follow-up evaluation included clinical assessment, laboratory tests, transthoracic echocardiography and cardiopulmonary exercise testing. Baseline and clinical follow-up data were compared using the Wilcoxon signed-rank test. ResultsA total of 24 patients (60.8 years, 83% male, mean left ventricular ejection fraction [LVEF] 24%), with a median of 1.5 HF hospitalizations in the previous six months, were referred for outpatient levosimendan pulses, the majority as a bridge to transplantation or due to clinical deterioration. At six-month follow-up there was a significant reduction in HF hospitalizations to 0.4±0.7 (p<0.001). NYHA class IV (52.2% to 12.5%, p=0.025) and NT-proBNP (8812.5 to 3807.4 pg/ml, p=0.038) were also significantly reduced. Exercise capacity was significantly improved, including peak oxygen uptake (p=0.043) and VE/VCO2 slope (p=0.040). LVEF improved from 24.0% to 29.7% (p=0.008). No serious adverse events were reported. ConclusionRepeated levosimendan administration in advanced HF patients is a safe procedure and was associated with a reduction in HF hospitalizations, functional and LVEF improvement, and reduction in NT-proBNP levels during follow-up.

SGLT2 Inhibition in Heart Failure with Preserved Ejection Fraction - The New Frontier.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with high morbidity and increasing socio-economic burden, compounded by the lack of effective treatment options available to treat this disease. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have previously been shown to improve cardiovascular and renal outcomes in patients with type 2 diabetes and patients with heart failure with reduced ejection fraction (HFrEF). Recent major clinical trials with SGLT2 inhibitors, both empagliflozin and dapagliflozin, have now demonstrated improved cardiovascular outcomes in patients with HFpEF and a significant reduction in heart failure hospitalization. Current evidence shows a potential for cardiovascular benefits with SGLT2 inhibition that is consistent across the spectrum of ejection fraction, age, New York Heart Association (NYHA) functional class, natriuretic peptide levels and diabetes status. Although the cardioprotective mechanisms behind SGLT2 inhibition remain unclear, ongoing clinical studies aim to clarify the role of SGLT2 inhibitors on biomarkers of cardiac metabolism, diastolic function and exercise capacity in HFpEF. This article analyzes current clinical evidence from randomized controlled trials and meta-analyses and explores the potential cardioprotective mechanisms of SGLT2 inhibitors, while also looking towards the future of SGLT2 inhibition in HFpEF.

PS-C19-1: EFFECTS OF COMBINED SODIUM-GLUCOSE CO-TRANSPORTER-2 INHIBITORS AND LOOP DIURETICS ON SYSTOLIC BLOOD PRESSURE: SYSTEMATIC REVIEW AND META-ANALYSIS

Background and Objective: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are considered a standard of care in patients with heart failure, chronic kidney disease (CKD), and diabetes. They have substantial positive effects on cardiovascular and renal outcomes including reducing heart failure hospitalization and slowing glomerular filtration rate (GFR) decline. Loop diuretics, on the other hand, are commonly prescribed to manage volume expansion in patients with CKD and heart failure. However, the effects of combining SGLT2 inhibitors with loop diuretics are not consistent across different clinical trials. The purpose of our meta-analysis is to investigate the effect of combined SGLT2 inhibitors and loop diuretics on systolic blood pressure. Method: Using Pubmed, Scopus, Web of Science, VHL, metaRegister of Controlled Trials (mRCT), and Clinical trials.gov, a systematic review and meta-analysis of literature on the effect of adding SGLT2 inhibitors to loop diuretics on blood pressure were conducted. The comprehensive review covered randomized controlled trials (RCTs), non-randomized studies, prospective, retrospective, and post hoc investigations examining the effect of SGLT2 inhibitors on systolic blood pressure in healthy and heart failure patients. The outcome was calculated using Cohen's d formula as the standardized mean difference between the first group (SGLT2 inhibitors plus loop diuretics) and the second group (loop diuretics alone). To ensure the data's validity, a sensitivity analysis was conducted using just RCTs. Results: Eleven studies with a total of 3343 participants met all the analysis's inclusion criteria. The pooled standardized mean difference for all studies was -0.17, indicating that SGLT2 inhibitors may have a little effect on blood pressure reduction (p value = 0.06). When RCTs were excluded from the analysis, the pooled standardized mean difference was -0.10 with a p value of 0.40. Conclusion: Compared to loop diuretic alone, SGLT2 inhibitors combined with loop diuretics are not associated with a significant reduction in systolic blood pressure in patients with heart failure.

Ambulatory Pulmonary Artery Pressure Monitoring Reduces Costs and Improves Outcomes in Symptomatic Heart Failure: A Single-Centre Canadian Experience

BackgroundPulmonary artery pressure (PAP) monitoring reduces heart failure (HF) hospitalizations (HFHs) and improves quality of life in New York Heart Association (NYHA) class III HF. We evaluated the impact of PAP monitoring on outcomes and health spending in a Canadian ambulatory HF cohort. MethodsTwenty NYHA III HF patients underwent wireless PAP implantation at Foothills Medical Centre, Calgary, Alberta. Baseline, and 3-, 6-, 9-, and 12-month assessments of laboratory parameters, hemodynamics, 6-minute walk text and Kansas City Cardiomyopathy Questionnaire scores were collected. Healthcare costs 1 year pre- and post-implantation were collected from administrative databases. ResultsMean age was 70.6 years; 45% were female. Results were as follows: an 88% reduction in emergency room visits (P = 0.0009); an 87% reduction in HFHs (P < 0.0003); a 29% reduction in heart function clinic visits (P = 0.033), and a 178% increase in nurse calls (P < 0.0002). Questionnaire and 6-minute walk test scores at baseline vs last follow-up were 45.4 vs 48.4 (P = 0.48) and 364.4 vs 402.8 m (P = 0.58), respectively. Mean PAP at baseline vs follow-up was 31.5 vs 24.8 mm Hg (P = 0.005). NYHA class improved by at least one class in 85% of patients. Mean measurable HF-related spending preimplantation was CAD$29,814 per patient per year and postimplantation was CAD$25,642 per patient per year (including device cost). ConclusionsPAP monitoring demonstrated reductions in HFHs, and emergency room and heart function clinic visits, with improvements in NYHA class. Although further economic evaluation is needed, these results support the use of PAP monitoring as an effective and cost-neutral tool in HF management in appropriately selected patients in a publicly funded healthcare system.

Reflecting on the advancements of HFrEF therapies over the last two decades and predicting what is yet to come.

What was once considered a topic best avoided, managing heart failure with reduced ejection fraction (HFrEF) has become the focus of many drug and device therapies. While the four pillars of guideline-directed medical therapies have successfully reduced heart failure hospitalizations, and some have even impacted cardiovascular mortality in randomized controlled trials (RCTs), patient-reported outcomes have emerged as important endpoints that merit greater emphasis in future studies. The prospect of an oral inotrope seems more probable now as targets for drug therapies have moved from neurohormonal modulation to intracellular mechanisms and direct cardiac myosin stimulation. While we have come a long way in safely providing durable mechanical circulatory support to patients with advanced HFrEF, several percutaneous device therapies have emerged, and many are under investigation. Biomarkers have shown promise in not only improving our ability to diagnose incident heart failure but also our potential to implicate specific pathophysiological pathways. The once-forgotten concept of discordance between pressure and volume, the forgotten splanchnic venous and lymphatic compartments, have all emerged as promising targets for diagnosing and treating heart failure in the not-so-distant future. The increase in heart failure-related cardiogenic shock (CS) has revived interest in defining optimal perfusion targets and designing RCTs in CS. Rapid developments in remote monitoring, telemedicine, and artificial intelligence promise to change the face of heart failure care. In this state-of-the-art review, we reminisce about the past, highlight the present, and predict what might be the future of HFrEF therapies.

Clin-STAR corner: Practice changing advances in cardiology.

Although cardiovascular disease is the leading cause of death and major disability in older adults, older patients have been consistently under-represented in most cardiovascular clinical trials. This article summarizes the results of four trials published from 2020 to 2022 with practice-changing implications directly applicable to the care of older adults. The key findings from these trials were that: (1) an initial conservative approach to managing selected patients with stable ischemic heart disease is reasonable, even in the setting of moderate or severe ischemia; (2) empagliflozin is effective in reducing heart failure hospitalizations in patients with heart failure and preserved ejection fraction, with or without diabetes; (3) an individually tailored physical rehabilitation program reduces deconditioning and functional decline in older patients hospitalized with heart failure; and (4) restricting dietary sodium intake to less than 1500 mg/day is unlikely to improve outcomes in most patients with heart failure.

192 GLP1-RA AND HEART FAILURE-RELATED OUTCOMES IN PATIENTS WITH AND WITHOUT HISTORY OF HEART FAILURE: A SYSTEMATIC REVIEW AND METANALYSIS

Abstract Background GLP1-receptor agonists (GLP1-ra) are recently developed anti-diabetic drugs which have shown promising results in phase-3 cardiovascular (CV) outcomes trials in diabetic patients, demonstrating a reduction in major adverse cardiovascular events (MACE) and, possibly, in heart failure (HF) hospitalizations. However, whether these medications improve such outcomes in patients with a history of HF remains unknown. Methods All randomized, placebo-controlled trials of GLP1-ra (and predefined/post-hoc analysis) reporting CV outcomes stratified by HF history were searched in Pubmed from inception to August 31st, 2022. The primary outcome was HF hospitalizations. Secondary outcomes included MACE, CV death and a composite of HF hospitalization and CV death. The analysis was performed after stratifying for HF history. Odds-ratio (OR) and 95% confidence interval (CIs) were used as effect estimated and calculated via a random-effects model. P for interaction between subgroups were calculated via meta-regression analysis and a level of p&amp;lt;0.10 was considered as significant. Results Data from 6 trials and a total of 40300 patients (n=20127 GLP1-ra group, n=20173 placebo group) were included. GLP1-ra reduced HF hospitalizations in patients without HF history (OR 0.71, 95% CI 0.51-0.99) but had neutral effect on those with previous HF (OR 1.04, 95% CI 0.88–1.22, p-interaction=0.089). CV death was also reduced by intervention only in the group without history of HF (OR 0.81, 95% CI 0.71–0.92), as well as the composite of HF hospitalizations and CV death (OR 0.80, 95% CI 0.72–0.90). Indeed, no difference between treatment arms was found in the HF group for CV death (OR 0.99, 95% CI 0.82–1.18, p-interaction=0.18) and the composite of HF hospitalization or CV death (OR 1.02 95%CI 0.89–1.18, p-interaction=0.073). MACE reduction was similar in patients with (OR 0.87 95% CI 0.72–1.06) and without HF history (OR 0.84 95% CI 0.76–0.93, p-interaction = 0.75). Conclusion GLP1-ra do not reduce HF hospitalization and CV death in patients with history of HF, as the benefit on cardiovascular outcomes provided by this anti-diabetic class of drugs seems to be mainly limited to patients without HF history. Future studies focused on HF patients are needed to confirm such findings and clarify the limited efficacy of GLP1-ra in this relevant group of patients.

Clinical Outcomes in Conduction System Pacing Compared to Right Ventricular Pacing in Bradycardia

BackgroundConduction system pacing (CSP) provides more physiological ventricular activation than right ventricular pacing (RVP). ObjectivesThis study evaluated the differences in clinical outcomes in patients receiving CSP and RVP. MethodsConsecutive patients with pacemakers implanted for bradycardia from 2016 to 2021 in 2 centers were prospectively followed for the primary composite outcome of heart failure (HF) hospitalizations, upgrade to biventricular pacing, or all-cause mortality, stratified by ventricular pacing burden (Vp) . ResultsAmong 860 patients (mean age 74 ± 11 years, 48% female, 48% atrioventricular block), 628 received RVP and 231 received CSP (95 His-bundle pacing, 136 left bundle branch pacing). The primary outcome occurred in 217 (25%) patients, more commonly in patients with RVP than CSP (30% vs 13%, P < 0.001). In multivariable analyses, CSP was independently associated with 47% reduction of the primary outcome (adjusted hazard ratio [AHR]: 0.53; 95% CI: 0.29-0.97; P = 0.04) and HF hospitalization alone (AHR: 0.40; 95% CI: 0.17-0.95; P = 0.04), among only patients with Vp >20%. The incidence of the primary outcome was highest among RVP with Vp >20% and lowest in CSP with Vp >20% (35% vs 10%, P < 0.001). Compared with RVP with Vp >20%, both CSP with Vp >20% (AHR: 0.51; 95% CI: 0.28-0.91; P = 0.02) and all patients with Vp ≤20% (AHR: 0.73; 95% CI: 0.54-0.99; P = 0.04) were independently associated with reduced primary outcome, driven primarily by reductions in HF hospitalizations (P < 0.05). Event-free survival was similar between CSP with Vp >20% and those needing ≤20% Vp. ConclusionsCSP significantly reduced adverse clinical outcomes for bradycardic patients requiring ventricular pacing and should be the preferred pacing modality of choice.

Early administration of ivabradine in patients admitted for acute decompensated heart failure.

Heart rate (HR) control is important in heart failure (HF) patients with reduced ejection fraction, and ivabradine is indicated for patients with chronic HF and sinus rhythm. However, ivabradine is limited in initiation of ivabradine at acute stage of HF. This multi-institutional retrospective study enrolled 30,639 patients who were admitted for HF from January 01, 2013 to December 31, 2018 at Chang Gung Memorial Hospitals. After applying selection criteria, the eligible patients were divided into ivabradine and non-ivabradine groups according to the initiation of ivabradine at the index hospitalization. HR, clinical outcomes including HF hospitalization, all-cause hospitalization, mortality, the composite of cardiovascular (CV) death or HF hospitalization and newly developed atrial fibrillation, and left ventricular ejection fraction (LVEF) and left atrium size were compared between the ivabradine and non-ivabradine groups after inverse probability of treatment weighting (IPTW) analysis after 12 months. The HR at admission in the ivabradine group (n = 433) was 99.04 ± 20.69/min, compared to 86.99 ± 20.34/min in the non-ivabradine group (n = 9,601). After IPTW, HR was lower in the ivabradine group than that in the non-ivabradine group after 12 months (74.14 ± 8.53 vs. 81.23 ± 16.79 bpm, p = 0.079). However, there were no significant differences in HF hospitalization (HR = 1.02; 95% CI, 0.38-2.79), all-cause hospitalization (HR = 0.95; 95% CI, 0.54-1.68), mortality (HR = 0.87; 95% CI, 0.69-1.08), the composite of CV death or HF hospitalization (HR = 0.87; 95% CI, 0.69-1.08) and newly developed AF between the two groups. In addition, LVEF increased with time in both groups, but there were no significant differences during the observation period. Ivabradine was beneficial in controlling HR when initiated in patients with acute stage of HF, but it did not seem to provide any benefits in reducing HF hospitalization, all-cause hospitalization, and mortality in 1 year after discharge.

Effectiveness of sacubitril-varsartan versus angiotensin converting enzyme inhibitors in patients hospitalized for acute heart failure: a retrospective cohort study of the RICA registry.

Sacubitril-valsartan has been shown to reduce hospitalizations and mortality in patients with heart failure (HF) and reduced ejection fraction. The PIONEER-HF trial demonstrated that initiation of the drug during acute HF hospitalization reduced NT-proBNP levels and a post-hoc analysis of the trial found a reduction in HF hospitalizations and deaths. Real-life studies in the elderly population are scarce. The aim of our study was to assess the effectiveness of sacubitril-valsartan versus angiotensin converting enzyme inhibitors (ACEI) in elderly patients who initiate this treatment during hospitalization for acute HF. We conducted a retrospective cohort study using the Spanish acute heart failure registry (RICA) comparing rehospitalizations and deaths at 3 months and 1 year among patients aged 70 years or older who had initiated treatment with sacubitril-valsartan during hospitalization for acute HF versus those treated with ACEI. One hundred and ninety-nine patients hospitalized between October 2016 and November 2020 were included, with a median age of 82 years and high rate of comorbidity. Of these, 107 were treated with sacubitril-valsartan and 92 with ACEI. The adjusted OR for readmission for HF at 3 months was 0.906 (95% CI: 0.241-3.404) and for the combined variable readmission for HF or death at 3 months was 0.696 (95% CI: 0.224-2.167). The adjusted OR for HF readmission at one year was 0.696 (95% CI: 0.224 -2.167). and for the combined variable HF readmission or death at one year 0.724 (95% CI: 0.325-1.612). Treatment with sacubitril-valsartan initiated early in hospitalization for HF in elderly patients with high comorbidity was associated with a trend towards a reduction in readmissions and death due to HF compared to treatment with ACEI, which did not reach statistical significance either at 3 months or 1 year of follow-up.

Artificial Intelligence, Wearables and Remote Monitoring for Heart Failure: Current and Future Applications.

Substantial milestones have been attained in the field of heart failure (HF) diagnostics and therapeutics in the past several years that have translated into decreased mortality but a paradoxical increase in HF-related hospitalizations. With increasing data digitalization and access, remote monitoring via wearables and implantables have the potential to transform ambulatory care workflow, with a particular focus on reducing HF hospitalizations. Additionally, artificial intelligence and machine learning (AI/ML) have been increasingly employed at multiple stages of healthcare due to their power in assimilating and integrating multidimensional multimodal data and the creation of accurate prediction models. With the ever-increasing troves of data, the implementation of AI/ML algorithms could help improve workflow and outcomes of HF patients, especially time series data collected via remote monitoring. In this review, we sought to describe the basics of AI/ML algorithms with a focus on time series forecasting and the current state of AI/ML within the context of wearable technology in HF, followed by a discussion of the present limitations, including data integration, privacy, and challenges specific to AI/ML application within healthcare.

Sodium-Glucose Co-transporter 2 Inhibitors/Gliflozins: A New Miracle Therapy for Heart Failure Patients Irrespective of Diabetes Status?

Despite the existence of effective medicines, heart failure continues to be the largest cause of illness and death worldwide. As a prospective family of drugs with potential cardiovascular advantages in non-diabetic patients, sodium-glucose co-transporter 2 inhibitors (SGLT2-I) have recently come to the forefront. In this comprehensive study, we assessed the favorable cardiovascular outcomes of SGLT2-I in three sizable, randomized trials with both diabetic and non-diabetic populations. The results from these studies revealed a substantial reduction in heart failurehospitalizations and cardiovascular and all-cause deaths. To further support our assertion that SGLT2-I has the potential to be a novel addition to the standard treatment plan for heart failure, we also tried to assemble several post hoc and prespecified studies of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) study. The details of two clinical investigations that supported their use in acute decompensated heart failure were also examined, along with the most plausible mechanism of action generating their cardioprotective effects. Additionally, positive cardiovascular advantages were addressed in chronic heart failure with both preserved and reduced ejection fractions. The role of SGLT2-I in ST-elevation myocardial infarction (STEMI) and hypertrophic cardiomyopathy (HOCM) patients is currently being studied, and this research has the potential to be revolutionary. The purpose of this systematic review is to compile all information that supports the use of this life-saving drug in patients who do not have diabetes so that cardiac care can be improved globally.

Left bundle branch area pacing: A promising modality for cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is recognized as the first-line management for patients with heart failure (HF) and conduction disorders. As a conventional mode for delivering CRT, biventricular pacing (BVP) improves cardiac function and reduces HF hospitalizations and mortality, but there are still limitations given the high incidence of a lack of response rates. Alternative pacing methods are needed either for primary or rescue therapy. In recent years, conduction system pacing (CSP) has emerged as a more physiological pacing modality for simultaneous stimulation of the ventricles, including His bundle pacing (HBP) and left bundle branch pacing (LBBP). CSP activates the His-Purkinje system, allowing normal ventricular stimulation. However, HBP is technically challenging with a relatively low success rate, high pacing threshold, and failure to correct distal conduction abnormalities. Therefore, LBBP stands out as a novel ideal physiological pacing modality for CRT. Several non-randomized studies compared the feasibility and safety of LBBP with BVP and concluded that LBBP is superior to BVP for delivering CRT with a narrower QRS and greater improvements in left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) functional class. Concurrently, some studies showed lower and stable pacing thresholds and greater improvement of B-type natriuretic peptide (BNP) levels, as well as better mechanical synchronization and efficiency. LBBP ensures better ventricular electromechanical resynchronization than BVP. In this review, we discuss current knowledge of LBBP, compare LBBP with BVP, and explore the potential of LBBP to serve as an alternative primary therapy to realize cardiac resynchronization.

Abstract 10399: Population-Level Implications of Empagliflozin for Heart Failure With Preserved Ejection Fraction in the United States

Introduction: The indication for empagliflozin has been expanded to patients with heart failure (HF) and left ventricular ejection fraction (LVEF) &gt;40% after findings of significant reduction in HF hospitalizations (HFH) and cardiovascular mortality (CVM) in the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction) trial. Objective: To quantify the estimated United States population-level impact of reducing worsening HF events with empagliflozin in LVEF &gt;40%. Methods: A projected adult HF population (age &gt;18) eligible for empagliflozin, obtained using weighted data from the National Health and Nutritional Examination Survey (2015-2018) was mapped onto newly eligible LVEF distributions, &gt;40% overall and those &gt;40% to 65% from the Get With The Guidelines Heart Failure registry. Number needed to treat (NNT) at 3 years for worsening HF events (urgent HF visits, total HFH and CVM) and total HFH, were calculated using rate difference from the EMPEROR program to estimate population-level treatment effects. Results: A projected 4,794,524 adults with HF are eligible for empagliflozin therapy. The population was predominantly male (57%) and white (67%), with a mean age of 66 years. Of this total population, 2,619,248 would be estimated as newly eligible with LVEF &gt;40% and 2,310,960 with LVEF &gt;40% to 65%. A projected 923,426 (95% CI, 769,893 – 1,076,959) worsening HF events would be prevented across the LVEF spectrum with empagliflozin over 3 years, out of which 301,738 (95%CI: 251,570, 351,906) and 295,341 (95%CI: 246,236 – 344,446) would be prevented in LVEF &gt;40% and LVEF &gt;40% to 65% subgroups, respectively. Moreover, an estimated 614,179 (95% CI, 512,063 – 716295) total HFH events would be prevented across the LVEF spectrum, out of which 201,159 (95%CI: 167,713 – 234,604) and 218,386 (95%CI: 182,076 – 254,696) total HFH events would be prevented in LVEF &gt;40% and LVEF &gt;40% to 65% subgroups, respectively. Conclusions: In addition to the proven benefit in HF with LVEF ≤40%, optimal implementation of empagliflozin in the US for treatment of HF with LVEF &gt;40% has the potential to prevent/postpone an additional 300,000 worsening HF events over 3 years.

Abstract 11497: Mineralocorticoid Receptor Antagonists and Atrial Fibrillation: A Systematic Review and Meta-Analysis

Introduction: Medical therapies to prevent atrial fibrillation (AF) episodes and to reduce heart failure (HF) or cardiovascular (CV) death in patients with AF are limited. The role of mineralocorticoid receptor antagonists (MRAs) in this population is unclear. Objectives: We aimed to assess whether the effect of MRAs (e.g. spironolactone, eplerenone, finerenone) in reducing cardiovascular events differs in patients with and without AF, and to evaluate the efficacy of MRAs in reducing AF events. Methods: We searched MEDLINE, Embase, and CENTRAL to March 2022 for randomized controlled trials (RCT) comparing an MRA to placebo or usual care in patients with established cardiovascular disease or risk factors. Pairs of reviewers systematically screened the eligible studies and used random-effects models to combine data. Results: We identified 6 RCTs including 7,245 participants (1,791 with AF and 5,454 without AF) that assessed the effect of MRAs on a composite of HF hospitalization or CV death (Figure). MRAs had similar efficacy for reducing HF hospitalization/CV death in patients with a history of AF (HR 0.86, 95% CI: 0.52-1.42; I 2 =71%) as compared to those without a history of AF (HR 0.77, 95% CI: 0.62-0.96; I 2 =58%) - P for subgroup differences=0.69. There was no evidence of difference in the efficacy of MRAs in reducing HF hospitalization (P for subgroup differences=0.93) and CV death (P for subgroup differences=0.41) in patients with and without AF. We identified 21 RCTs including 22,126 participants that reported on the occurrence of AF events. MRAs significantly reduced AF events (RR 0.78, 95% CI: 0.71-0.87; I 2 =0%). This effect was similar for reducing both new-onset AF (RR 0.81, 95% CI: 0.64-1.01; I 2 =32%) and recurrent AF episodes (RR 0.77, 95% CI: 0.67-0.88; I 2 =0%) - P for subgroup differences=0.71. Conclusions: MRAs reduce HF hospitalization or CV death to a similar extent in patients with and without AF. In addition, MRAs may prevent new-onset and recurrent AF events.

ODP054 The Impact of SGLT2-inhibitors on Renin-Aldosterone axis and Adrenal Incidentaloma's work up: Case study and literature review

Abstract Introduction SGLT2 inhibitors (SGLT2i) are being increasingly used in patients with Type 2 DM given their glycemic effects along with cardio-protective and reno-protective effects. SGLT2i exert these effects through various mechanisms, mainly through the RAAS (Renin-Angiotensin-Aldosterone System) with diuresis, leading to transient elevation of renin levels with minimal effect on aldosterone levels. We present a case where elevated aldosterone levels improved stoppage of SGLT2i. Case 52 year male with history of GERD and Sleep apnea who was referred for evaluation of right adrenal incidentaloma of 2 cm found on CT abdomen in 12/2019 as part of renal stone work up. Initial work up in 3/2020 showed elevated aldosterone of 87.1, renin of 2.3 with ratio of 37.9. Repeat work up in 7/2020 showed elevated aldosterone of 66 with renin levels of 2. High urine aldosterone of 64.7 was noted but urine sodium of 171 mg only. Urine metanephrine and normetanephrine levels were in the reference range. He was started on spironolactone considering hyperaldosteronism and mild hypertension, but developed hyperglycemia and type 2 diabetes mellitus which was initially treated with insulin and later switched to Jardiance. Follow up CT abdomen with adrenal protocol in 8/2020 showed stable right adrenal nodule, consistent with adrenal adenoma. His repeat aldosterone levels remained elevated at 70 with renin levels of 2.8 in 6/2021 after holding spironolactone for 2 weeks. Patient was advised to stop Jardiance as well as continue holding Spironolactone in 9/2021 and repeated labs showed an improvement in aldosterone levels of 43 in 10/2021 and 21 in 12/2021 with renin levels of 2.79 and 2.95 respectively. Discussion SGLT2 inhibitors are known to reduce heart failure hospitalization in the clinical trials. Use of SGLT2i leads to early diuresis with natriuresis and systemic RAAS activation rather than intra-renal RAAS activation. Effects are mainly mediated through transient natriuresis with volume depletion in short term, leading to RAAS activation with transient renin elevation but no significant effects on aldosterone levels, possibly due to other controlling factors like ACTH and K levels along with circadian rhythm. Our case presents unique scenario where elevated aldosterone with normal (non-suppressed) renin levels were noted in the context of adrenal incidentaloma work up and Jardiance use. Even though the improvement of aldosterone levels might be related to multiple factors but with increasing use of SGLT2i, much attention should be paid to the impact of these agents on renin-aldosterone axis and possible need of holding these agents if elevated renin-aldosterone levels are noted. Presentation: No date and time listed

Catheter ablation improves cardiovascular outcomes in patients with atrial fibrillation and heart failure: a meta-analysis of randomized controlled trials.

The effect of atrial fibrillation catheter ablation on cardiovascular outcomes in heart failure is an important outstanding research question. We undertook a meta-analysis of randomized controlled trials comparing ablation to medical therapy in patients with AF and heart failure. We systematically identified all trials comparing catheter ablation to medical therapy in patients with heart failure and atrial fibrillation. The pre-specified primary endpoint was all-cause mortality in trials with at least 2 years of follow-up. The secondary endpoint was heart failure hospitalization. Sensitivity analyses were performed for trials with any follow-up and trials deemed at low risk of bias. Eight trials (1390 patients) were included. Seven hundred and seven patients were randomized to catheter ablation and 683 to medical therapy. In the primary analysis (three trials, n = 977), catheter ablation reduced mortality compared with medical therapy [relative risk (RR): 0.61, 95% confidence interval (CI): 0.44 to 0.84, P = 0.003]. Catheter ablation also reduced heart failure hospitalizations compared with medical therapy (RR: 0.60, 95% CI: 0.49-0.74, P < 0.001). The effect on stroke was not statistically significant (RR: 0.62, 95% CI: 0.28-1.37, P = 0.237). There was low heterogeneity between studies. Sensitivity analyses were consistent with the primary analyses. In patients with atrial fibrillation and heart failure, catheter ablation reduces mortality and the occurrence of heart failure hospitalizations.

Reduction in heart failure hospitalizations by sacubitril/valsartan; a post-hoc analysis of the PARALLAX trial

Abstract Background The PARALLAX trial recently showed a significant reduction in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations by angiotensin receptor neprilysin inhibition with sacubitril/valsartan (S/V) compared to standard medical therapy (SMT) in patients with heart failure and ejection fraction ≥40%. As NT-proBNP reductions have been associated with a reduction in future heart failure hospitalizations (HHF), we aimed to investigate the impact of S/V on this endpoint in comparison to standard medical therapy. Methods The PARALLAX study was a 24-week, randomized, active-controlled, parallel group study to evaluate S/V compared to SMT for comorbidities. Eligible patients were stratified into three strata according to their individual RASi treatment (ACEi, ARB, ACEi/ARB-naïve) and randomized within each stratum 1:1 to S/V (N=1281; target dose (td), 97/103 mg b.i.d.) or individual comparator (N=1285; enalapril (td 10 mg b.i.d), valsartan (160 mg b.i.d.), or placebo). Hospitalizations for cardiac failure reported as serious adverse events by investigators were analysed in this post-oc secondary analysis. Results 2566 patients with heart failure and LVEF ≥40%, were randomized to receive either S/V or SMT according to RASi stratum (n=1,016 ACE inhibitor stratum, n=1,174 ARB stratum, n=326 no RAS stratum). After 12 weeks, adjusted geometric mean ratio of NT-proBNP showed a 16.4% greater reduction sith S/V vs. SMT (p&amp;lt;0.0001). S/V reduced the risk for cardiac failure events leading to hospitalization by 51% (hazard ratio (HR) 0.49; 95% CI 0.30, 0.81; p=0.005). Similar results were obtained in all three strata: HR 0.55 (0.25–1.19) in ACE inhibitor stratum, HR 0.50 (024–1.02) in ARB stratum and HR 0.37 (0.10–1.38) in no RAS stratum. Conclusion The significant reduction of NT-proBNP plasma levels by S/V in comparison to SMT in PARALLAX was associated with a significant reduction in heart failure hospitalisations. These results, together with evidence from the PARAGON trial, support the use of S/V in HFpEF for avoiding heart failure hospitalizations. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novartis

Efficacy of sodium glucose cotransporter 2 inhibitors for heart failure with preserved and mildly reduced ejection fraction: a systematic review and meta-analysis

Abstract Background SGLT2 inhibition has been a breakthrough approach in the treatment for heart failure. A recent guideline has recommended SGLT2i for the treatment of patients with HFrEF to reduce the risk of HF hospitalization and death, regardless of presence of type 2 diabetes (1). However, its benefit in HFpEF and HFmrEF have yet to be established. Purpose We evaluated the cardiovascular outcomes of SGLT2i for HFpEF and HFmrEF. Methods Randomized controlled trials on SGLT2i versus placebo in patients with left ventricular ejection fraction of more than 40% reporting CV outcomes were searched using Pubmed, CENTRAL, and ScienceDirect. Primary outcome was the composite of hospitalization for heart failure or CV death. Secondary outcomes were the individual HHF, CV death, as well as all-cause mortality. Pooled hazard ratios with 95% confidence intervals were used as effect estimates using fixed-effects model. Results Six studies were included with a total of 10,450 patients. In the combined HFmrEF and HFpEF population, there was a significant reduction in composite of cardiovascular death and heart failure hospitalization in the SGLT2i group (HR 0.79, 95% CI 0.71–0.88, p&amp;lt;0.0001) compared to placebo, driven by a significant reduction in heart failure hospitalization (HR 0.73, 95% CI 0.63–0.84, p&amp;lt;0.00001). In the distinct HFpEF population, there was a significant reduction in composite of cardiovascular death and heart failure hospitalization in the SGLT2i group (HR 0.75, 95% CI 0.63–0.88, p=0.0007) compared to placebo. Conclusion SGLT2i provides significant risk reduction in HF hospitalization or CV death among patients with HFpEF compared to placebo. Funding Acknowledgement Type of funding sources: None.

Impact of sodium-glucose co-transporter 2 inhibitors on cardiovascular outcomes in patients with chronic kidney disease: Hong Kong-wide, observational, propensity score matched analysis

Abstract Purpose The impact of SGLT2i on patients with advanced chronic kidney disease (CKD) is limited. We aimed to compare hospitalization for heart failure (HHF) and cardiovascular (CV) death between new users of SGLT2i versus non-users across the spectrum of CKD stages. Methods We retrospectively analyzed 22,657 patients with CKD who were prescribed SGLT2i between August 2015 and August 2020 in 16 public hospitals in Hong Kong. Propensity-matched cohorts of SGLT2i users and non-users (n=3,704 per group) were generated on the basis of age, gender, baseline eGFR, co-morbidities and medications. Time to HHF and CV death was analyzed using COX proportional hazards model. Subgroup analysis was performed to detect heterogeneity of effect across stages of CKD. Results Of the whole cohort (N=22,657), the percentage of SGLT2i users in CKD stage G1 to G5 were 82.1%, 49.0%, 19.8%, 10.3%, 4.3%, and 1.6%, respectively. SGLT2i users and non-users groups were well balanced at baseline (mean age 64.7±12.7, female 37.1%), with a median follow-up of 2.8 (IQR: 1.1–5.1) years (22876.5 person-years). Overall, SGLT2i was associated with reduced risk of HHF (Hazards Ratio (HR) 0.12 (95% CI (0.10–0.16) and CV death (HR 0.17 (95% CI (0.12–0.25), compared with non-users. Subgroup analysis demonstrated benefit of SGLT2i on CV death in G3 to G5 groups but not in patients in earlier CKD stages (P for interaction &amp;lt;0.001) (Table). Reduction in risk of HHF was comparable across all CKD stages (P for interaction = 0.1). Conclusion Utilization of SGLT2i was associated with significant reduction in HHF and CV death in patients with moderate to severe CKD in a real-world setting. Our results suggest significant heterogeneity in CV death reduction with the largest benefit in patients with stage G3a and more advanced CKD. Funding Acknowledgement Type of funding sources: None.