Hospitalization For Failure Research Articles

Comparative analysis of renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitor and mineralocorticoid receptor antagonists in heart failure with mildly reduced ejection fraction

Abstract Background Apart from sodium-glucose co-transporter 2 inhibitors, the efficacy of renin–angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI)j8788 as well as mineralocorticoid receptor antagonist (MRA) in patients with heart failure with mildly reduced ejection fraction remains uncertain. We assessed the association between these medications and outcomes in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Methods Patients with HFmrEF from our university hospital-integrated Medical Database were included. Associations between the medications and cardiovascular mortality/heart failure hospitalization were evaluated using Cox regressions in a 1:1 propensity score-matched cohort. Inverse probability of treatment weighting was employed to balance baseline patient characteristics. Results Of 2584 patients with HFmrEF, 17% received MRA and 43% received RASI/ARNI. Predictors of MRA use included older age, slightly higher ejection fraction, lower NT-proBNP level, and eGFR >60 mL/min/1.73 m^2. Predictors of RASI/ARNI use included higher body mass index, lower NT-proBNP level, normal uric acid level, normal potassium level, and eGFR >60 mL/min/1.73 m^2. MRA use was not associated with a lower risk of cardiovascular death and hospitalization for heart failure (hazard ratio [HR] = 0.89, 95% confidence interval [CI]: 0.78–1.02 and HR = 1.01, 95% CI: 0.94–1.09, respectively). Conversely, RASI/ARNI use was associated with a lower risk of cardiovascular death but not hospitalization for heart failure (HR = 0.82, 95% CI: 0.71–0.94 and HR = 0.995, 95% CI: 0.924–1.07, respectively). Notably, landmark analysis revealed no significant difference in the risk of outcomes when the follow-up duration exceeded two years. Conclusions The effect of MRA on cardiovascular death and hospitalization for heart failure was neutral, whereas RASI/ARNI was associated with a lower risk of cardiovascular death. Our findings suggest that RASi use may be more beneficial than MRA use in patients with HFmrEF.

Clinical Factors Affecting Survival in Patients with Congenitally Corrected Transposition of the Great Arteries: A Systematic Review and Meta-Analysis.

Background: Congenitally corrected transposition of the great arteries (cc-TGA) is a defect characterized by arterio-ventricular and atrioventricular disconcordance. Most patients have co-existing cardiac abnormalities that warrant further treatment. Some patients do not require surgical intervention, but most undergo physiological repair or anatomical surgery, which enables them to reach adulthood. Aims: We aimed to evaluate mortality risk factors in patients with cc-TGA. Results: We searched the PubMed database and included 10 retrospective cohort studies with at least a 5-year follow-up time with an end-point of cardiovascular death a minimum of 30 days after surgery. We enrolled 532 patients, and 83 met the end-point of cardiovascular death or equivalent event. As a risk factor for long-term mortality, we identified New York Heart Association (NYHA) class ≥III/heart failure hospitalization (OR = 10.53; 95% CI, 3.17-34.98) and systemic ventricle dysfunction (SVD; OR = 4.95; 95% CI, 2.55-9.64). We did not show history of supraventricular arrhythmia (OR = 2.78; 95% CI, 0.94-8.24), systemic valve regurgitation ≥moderate (SVR; OR = 4.02; 95% Cl, 0.84-19.18), and pacemaker implantation (OR = 1.48; 95% Cl, 0.12-18.82) to affect the long-term survival. In operated patients only, SVD (OR = 4.69; 95% CI, 2.06-10.71) and SVR (OR = 3.85; 95% CI, 1.5-9.85) showed a statistically significant impact on survival. Conclusions: The risk factors for long-term mortality for the entire cc-TGA population are NYHA class ≥III/heart failure hospitalization and systemic ventricle dysfunction. In operated patients, systemic ventricle dysfunction and at least moderate systemic valve regurgitation were found to affect survival.

Comparative cardiovascular benefits of individual SGLT2 inhibitors in type 2 diabetes and heart failure: a systematic review and network meta-analysis of randomized controlled trials.

In patients with type 2 diabetes (T2D) and a history of heart failure (HF), sodium-glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated cardiovascular (CV) benefits. However, the comparative efficacy of individual SGLT2is remains uncertain. This network meta-analysis (NMA) compared the efficacy and safety of five SGLT2is (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and sotagliflozin) on CV outcomes in these patients. PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched up to September 23, 2022, to identify all randomized controlled trials (RCTs) comparing SGLT2is to placebo in T2D patients with HF. The main outcomes included composite CV death/heart failure hospitalization (HFH), HFH, CV death, all-cause mortality, and adverse events. Pairwise and NMA approaches were applied. Our analysis included 11 RCTs with a total of 20,438 patients with T2D and HF. All SGLT2is significantly reduced HFH compared to standard of care (SoC) alone. "Add-on" SGLT2is, except ertugliflozin, significantly reduced composite CV death/HFH relative to SoC alone. Moreover, canagliflozin had lower composite CV death/HFH compared to dapagliflozin. Based on the surface under the cumulative ranking curve (SUCRA), the top-ranked SGLT2is for reducing HFH were canagliflozin (95.5%), sotagliflozin (66.0%), and empagliflozin (57.2%). Head-to-head comparisons found no significant differences between individual SGLT2is in reducing CV death. "Add-on" SGLT2is reduced all-cause mortality compared with SoC alone, although only dapagliflozin was statistically significant. No SGLT2is were significantly associated with serious adverse events. A sensitivity analysis focusing on HF-specific trials found that dapagliflozin, empagliflozin, and sotagliflozin significantly reduced composite CV death/HFH, consistent with the main analysis. However, no significant differences were identified from their head-to-head comparisons in the NMA. The SUCRA indicated that sotagliflozin had the highest probability of reducing composite CV death/HFH (97.6%), followed by empagliflozin (58.4%) and dapagliflozin (44.0%). SGLT2is significantly reduce the composite CV death/HFH outcome. Among them, canagliflozin may be considered the preferred treatment for patients with diabetes and a history of heart failure, but it may also be associated with an increased risk of any adverse events compared to other SGLT2is. However, a sensitivity analysis focusing on HF-specific trials identified sotagliflozin as the most likely agent to reduce CV death/HFH, followed by empagliflozin and dapagliflozin. https://www.crd.york.ac.uk/prospero/, identifier CRD42022353754.

Validating the association between a composite metric of guideline-directed medical therapy (GDMT) and clinical outcomes for patients with heart failure with reduced ejection fraction (HFrEF)

Abstract Introduction A composite metric to characterize the overall quality of GDMT for patients with HFrEF is important to evaluate quality-of-care and for clinical research. Purpose We sought to evaluate the associations between GDMT scores and cardiovascular outcomes amongst patients with recently-diagnosed HFrEF within a large national integrated health system within the United States. Methods We identified a cohort of patients with recent-onset HFrEF who received care within the Veterans Affairs system between January 2013 and June 2019. We excluded patients with systolic blood pressure <100mmHg or glomerular filtration rate <30 mL/min/1.73m2. We identified active medical therapy based on the last medication fill 90-180 days after the index date (first date with documented HF diagnosis and EF≤40%). We calculated three different GDMT scores: the original Heart Failure Collaboratory Score, the 4-Pillar Intensification Score, and a modified 4-Pillar Intensification Score that included continuous scoring to further incentivize dose uptitration (Figure 1). Using a landmark analysis, we evaluated the association between a 1 standard deviation (SD) change in the GDMT scores at 6 months with the following outcomes: all-cause death, cardiovascular death, and the composite of cardiovascular death/heart failure hospitalization. We repeated the analyses with adjustment for comorbidities and vital signs. Results Among 108,752 patients with recent-onset HFrEF, the mean age was 70.0 years (SD: 11.1) and 97.6% were men. Treatment rates were the following: evidence-based beta-blockers – 55.2%, renin-angiotensin system inhibitors – 60.2%, angiotensin neprilysin inhibitors – 2.9%, mineralocorticoid receptor antagonists – 17.6%, sodium glucose transporter 2 inhibitors – 0.7%, hydralazine/nitrates – 4.9%, and ivabradine – 0.1%. A one standard deviation increase in each of the GDMT scores was associated with improved clinical outcomes (Table 1). Figure 1 illustrates the association between the modified 4-Pillar Intensification Score and the composite of cardiovascular death/heart failure hospitalization. These associations were attenuated but remained significant with comorbidity adjustment. Results also remained consistent when the study period was restricted to 2016 or later and with inclusion of the last prescription fill between 1-180 days post-index date. Conclusion Our study suggests that GDMT scores are consistently associated with clinical outcomes among patients with HFrEF.

Clinical factors affecting survival in patients with D-transposition of the great arteries after atrial switch repair: A meta-analysis.

Atrial switch repair (AtrSR) was the initial operation method in patients with D-transposition of the great arteries (D-TGA) constituting the right ventricle as a systemic one. Currently, it has been replaced with arterial switch operation (ASO), but the cohort of adults after AtrSR is still large and requires strict cardiological management of late complications. For this reason, we aimed to evaluate potential long-term mortality risk factors in patients with D-TGA after AtrSR (either Mustard or Senning procedures) Methods: We searched the MEDLINE database for suitable trials. We included 22 retrospective and prospective cohort studies of patients with D-TGA with at least 5 years mean/median follow-up time after Mustard or Senning procedures, with an endpoint of non-sudden cardiac death (n-SCD) and sudden cardiac death (SCD) after at least 30 days following surgery. A total of 2912 patients were enrolled, of whom 351 met the combined endpoint of n-SCD/SCD. The long-term mortality risk factors were New York Heart Association (NYHA) class ≥III/heart failure hospitalization (odds ratio [OR], 7.25; 95% confidence interval [CI], 2.67-19.7), tricuspid valve regurgitation (OR, 4.64; 95% CI, 1.95-11.05), Mustard procedure (OR, 2.15; 95% CI, 1.37-3.35), complex D-TGA (OR, 2.41; 95% CI, 1.31-4.43), and right ventricular dysfunction (OR, 1.94; 95% CI, 0.99-3.79). Supraventricular arrhythmia (SVT; OR, 2.07; 95% CI, 0.88-4.85) and pacemaker implantation (OR, 2.37; 95% CI, 0.48-11.69) did not affect long-term survival in this group of patients. In an additional analysis, SVT showed a statistically significant impact on SCD (OR, 2.74; 95% CI, 1.36-5.53) but not on n-SCD (OR, 1.5; 95% CI, 0.37-6.0). This meta-analysis demonstrated that at least moderate tricuspid valve regurgitation, NYHA class ≥III/heart failure hospitalization, right ventricular dysfunction, complex D-TGA, and Mustard procedure are risk factors for long-term mortality in patients after AtrSR.

115 DIURETIC DOSE TRAJECTORIES IN DILATED CARDIOMYOPATHY: PROGNOSTIC IMPLICATIONS

Abstract Background For patients with heart failure, prescription of loop diuretics (LD) and higher doses are associated with adverse prognosis. We investigated LD dose trajectories and their associations with outcomes in patients with dilated cardiomyopathy (DCM). Methods Associations between outcomes and both furosemide equivalent dose (FED) at enrolment and change in FED in the subsequent 24 months were evaluated. According to FED trajectory, patients were divided in i) dose↑ (FED increase by ≥50% or newly initiated); ii) dose↓ (FED decrease by ≥50%); iii) stable dose (change in FED by <50%); iv) never-users. Primary outcome was all-cause-death/heart transplantation/ventricular-assist-device/heart failure hospitalization. Secondary outcome was all-cause-death/heart transplantation/ventricular-assist-device. Results Of 1,131 patients enrolled, 738 (65%) were prescribed LD at baseline. Baseline FED was independently associated with outcome (HR per 20mg increase: 1.12 [95% CI 1.04-1.22, p=0.003]. Of the 908 with information on FED within 24 months from enrolment, 31% were never-users; 29% dose↓; 26% stable dose and 14% dose↑. In adjusted models, compared to never-users, stable dose had a higher risk of primary outcome (HR 2.42 [95% CI: 1.19-4.93], p=0.015), while dose↑ had the worst prognosis (HR 2.76 [95% C.I. 1.27-6.03], p=0.011). The results were consistent for the secondary outcome. Compared to patients who remained on LD, discontinuation of LD (143, 24%) was associated with improved outcome (HR 0.43 [95% C.I. 0.28-0.65], p<0.001). Conclusions In a large cohort of patients with DCM, LD use and increasing FED are powerful markers of adverse outcomes. Patients who never require LD have an excellent prognosis.

Diuretic dose trajectories in dilated cardiomyopathy: prognostic implications

BackgroundFor patients with heart failure, prescription of loop diuretics (LD) and of higher doses are associated with an adverse prognosis. We investigated LD dose trajectories and their associations with outcomes in patients with dilated cardiomyopathy (DCM).MethodsAssociations between outcomes and both furosemide-equivalent dose (FED) at enrolment and change in FED in the subsequent 24 months were evaluated. According to FED trajectory, patients were classified as (i) dose↑ (FED increase by ≥ 50% or newly initiated); (ii) dose↓ (FED decrease by ≥ 50%); (iii) stable dose (change in FED by < 50%); and (iv) never-users. The primary outcome was all-cause-death/heart transplantation/ventricular-assist-device/heart failure hospitalization. The secondary outcome was all-cause-death/heart transplantation/ventricular-assist-device.ResultsOf 1,131 patients enrolled, 738 (65%) were prescribed LD at baseline. Baseline FED was independently associated with outcome (HR per 20 mg increase: 1.12 [95% CI 1.04–1.22], p = 0.003).Of the 908 with information on FED within 24 months from enrolment, 31% were never-users; 29% were dose↓; 26% were stable dose and 14% were dose↑. In adjusted models, compared to never-users, stable dose had a higher risk of the primary outcome (HR 2.42 [95% CI 1.19–4.93], p = 0.015), while dose↑ had the worst prognosis (HR 2.76 [95% CI 1.27–6.03], p = 0.011). Results were similar for the secondary outcome. Compared to patients who remained on LD, discontinuation of LD (143, 24%) was associated with an improved outcome (HR 0.43 [95% CI 0.28–0.65], p < 0.001).ConclusionsIn patients with DCM, LD use and increasing FED are powerful markers of adverse outcomes. Patients who never receive LD have an excellent prognosis.Graphical abstractAmong 1131 DCM patients 65% received loop diuretics at enrolment (upper left side). The bar chart on the upper right side shows the categorization in never-users/ dose↓/stable dose/ dose↑ over 24 months of follow-up. At the bottom is reported on the left side of each panel (observation period) the trajectory of LD dose in the four groups (left panel) and in patients who have their LD suspended vs those who continue LD (right panel) in the first two years. On the right side of each panel is shown the incidence of primary outcomes during the subsequent follow-up in the subgroups (outcome assessment)

Clinical factors affecting survival in patients with D-transposition of the great arteries after atrial switch repair: a meta-analysis

Abstract Background Atrial switch repair (AtrSR) was the initial method of operation in patients with D-transposition of the great arteries (D-TGA) constituting the right ventricle as a systemic one. Currently, it has been replaced with arterial switch operation (ASO), but the cohort of adults after AtrSR is still large and requires strict cardiological management of late complications. For this reason, we aimed to evaluate potential long-term mortality risk factors in patients with D-TGA after AtrSR (either Mustard or Senning procedure) Method We searched MEDLINE database for suitable trials. We included 22 retrospective and prospective cohort studies of patients with D-TGA with at least 5 years mean/median follow-up time after Mustard or Senning procedure, with an end-point of non-sudden cardiac death (n-SCD) and sudden cardiac death (SCD) after at least 30 days after surgery. Results A total of 2912 patients were enrolled, of which 351 met the combined endpoint of n-SCD/SCD. The long-term mortality risk factors were: NYHA&amp;gt;II/heart failure hospitalization (OR=7.25; p=0.0001), tricuspid valve regurgitation (OR=4.64; p=0.0005), Mustard procedure (OR=2.15; p=0.0008), complex D-TGA (OR=2.41; p=0.005), right ventricle dysfunction (OR=1.94; p=0.05). Supraventricular arrhythmia (SVT; OR=2.07; p=0.09) and pacemaker implantation (OR=2.37; p=0.29) did not affect long-term survival in this group of patients. In an additional analysis, SVT showed a statistically significant impact on SCD (OR=2.74; p=0.005) but not on n-SCD (OR=1.5; p=0.57). Conclusions This meta-analysis identified that at least moderate tricuspid valve regurgitation, NYHA class &amp;gt; II/heart failure hospitalization, right ventricle dysfunction, complex D-TGA and Mustard procedure as risk factors of long-term mortality in patients after AtrSR. Funding Acknowledgement Type of funding sources: None.

Association between use of renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors and beta-blockers and outcome in real-world heart failure and mildly reduced ejection fraction

Abstract Background In heart failure with mildly reduced ejection fraction (HFmrEF) European guidelines recommend the use of antineurohormonal therapies with a low level of evidence (IIb C) based on data from subgroup and post-hoc analyses of randomized clinical trials (RCTs). Data from large and unselected real-world HFmrEF populations are lacking. Purpose To assess the association between renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI) and beta-blockers and outcomes in HFmrEF. Methods Data from patients with HFmrEF (EF: 40–49%) from the Swedish HF Registry during 2000–2018 were considered. The association between each of RASI/ARNI and beta-blockers treatment and cardiovascular (CV)mortality/heart failure hospitalization (HFH) and all-cause mortality was assessed by Cox proportional hazard models in a 1:1 propensity score-matched cohort. Since propensity score (PS) matching might lead to a selection of the study population and reduction of the sample size, as consistency analysis Cox proportional hazard models were also fitted in the overall cohort adjusting rather than matching for PS. Results Of 12421 patients with HFmrEF (mean age 74±12 years, 64% males), 10419 (84%) received RASI/ARNI, 10941 (88%) received beta-blockers. Patients treated with both RASI/ARNI and beta-blockers were 9332 (75%), 2696 (22%) patients received one drug (9% RASI/ARNI, 13% beta-blockers) and 393 (3%) none. Main predictors of treatments use were younger age, female sex (only for beta-blockers), outpatient setting, referral to specialty care and nurse-led HF clinic. Lower NT-proBNP levels were associated with more use of RASI/ARNI but less use of beta-blockers. Better renal function was predictive of RASI/ARNI use. Comorbidities were associated with less use of treatments, in particular atrial fibrillation for RASI/ARNI, and COPD for RASI/ARNI and beta-blockers. In the matched cohorts including 3854 for RASI/ARNI analyses and 2940 patients for beta-blockers, RASI/ARNI (HR=0.90, 95% CI: 0.83–0.97) and beta-blocker (HR=0.82, 95% CI: 0.75–0.91) use were associated with a statistically significant lower risk of CV mortality/HF hospitalization (Figure 1) and of all-cause mortality (HR=0.72, 95% CI: 0.67–0.78 and HR=0.77, 95% CI: 0.70–0.85, respectively). Consistency analysis confirmed results. Conclusions RASI/ARNI and beta-blockers were largely used in this large real-world cohort of patients with HFmrEF to treat comorbidities. Their use was associated with lower risk of mortality/morbidity and the magnitude of the associations was somehow similar to what observed in subgroup/post-hoc analyses of RCTs. Our findings call for a fast implementation of guidelines recommendations on HFmrEF treatment. Funding Acknowledgement Type of funding sources: None.

438-P: Cardiorenal Benefits of Newer Glucose-Lowering Drugs by Hispanic Ethnicity: A Meta-analysis of Results from Randomized Outcome Trials in Type 2 Diabetes

Background: Hispanic individuals are at increased risk of diabetes and related complications compared to non-Hispanic White individuals. Thus, we aimed to compare cardiorenal outcomes of newer glucose-lowering drugs between Hispanic and non-Hispanic populations via a meta-analysis of randomized outcome trials. Methods: We included randomized placebo-controlled cardiovascular (CV) and renal outcome trials of SGLT2 inhibitors, GLP-1RAs, and DPP-4 inhibitors that reported major adverse cardiovascular events (MACE) , CV death/heart failure hospitalization (HHF) , or composite renal outcome, stratified by the Hispanic ethnicity (Hispanic vs. non-Hispanic) . We calculated pooled hazard ratios (HR) with 95% CI using fixed-effects models and tested the differences between the two groups (Pinteraction ) . Results: We included outcome trials reporting outcomes by Hispanic ethnicity in 89,393 patients with type 2 diabetes. In three SGLT2 inhibitor trials, the risk of MACE varied by ethnicity (HR = 0.70 [0.54-0.91] in Hispanic population and HR = 0.96 [0.86-1.07] in non-Hispanic population) with a Pinteraction = 0.03, while the risks of CV death/HHF (Pinteraction = 0.46) and composite renal outcome (Pinteraction = 0.31) were similar across ethnicity. In five GLP-1RA trials, we observed a similar MACE risk between Hispanic (HR = 0.82 [0.70-0.96]) and non-Hispanic (HR = 0.92 [0.84-1.00]) populations (Pinteraction = 0.22) . In three DPP-4 inhibitor trials, the risk of MACE was greater in Hispanic (HR=1.15 [0.98-1.35]) than non-Hispanic (HR= 0.96 [0.88-1.04]) populations (Pinteraction = 0.045) , while the risk of composite renal outcome was similar between the two groups (Pinteraction = 0.51) . Conclusion: Compared with non-Hispanic individuals, Hispanics with type 2 diabetes obtain a greater benefit on lowering MACE risk with the use of SGLT2 inhibitors, while a lower benefit with DPP-4 inhibitors. Disclosure H.Tang: None. W.Chen: None. J.Bian: None. L.J.O'neal: None. D.T.Lackland: None. D.Schatz: Advisory Panel; Abbott Diabetes, Medtronic. J.Guo: None.

130-LB: Linagliptin vs. Sitagliptin for Type 2 Diabetes Inpatient Glycemic Management and Cardiovascular Outcomes—Is There a Difference between DPP-4 Inhibitors?

Background: Oral DPP-4 inhibitors provide adjunctive therapy to insulin in hospitalized patients with blood glucose (BG) &amp;lt; 400 mg/dL. Results from trials comparing sitagliptin or linagliptin to basal-bolus insulin showed mixed results, with no head-to-head comparison between sitagliptin and linagliptin. The aim of this study is to provide new evidence on their comparative efficacy and safety. Methods: This was a retrospective, single-center, observational study of hospitalized general medicine and surgery adult patients with type 2 diabetes. Patients who received at least 2 doses of linagliptin or sitagliptin between January and December 2019 were assigned to either arms. Primary endpoint was the difference in mean daily BG. Secondary endpoint was a composite of 3-point major adverse cardiac events (MACE) and heart failure (HF) hospitalization. Safety endpoints included the number of hypoglycemic events (BG &amp;lt; 70 mg/dL) and the appropriateness of dosing based on eGFR. Results: A total of 100 patients were included. The mean daily BG was similar in the linagliptin arm (167.6 ± 43.5 mg/dL) compared to the sitagliptin arm (162.1 ± 37.5 mg/dL) (p=0.5) . In a subgroup analysis, patients who received linagliptin plus correctional insulin had more BG readings within the range of 140-180 mg/dL (50% vs. 36%, p=0.2) . The composite of 3-point MACE and HF hospitalization was similar between both arms. Hypoglycemia occurred more frequently with linagliptin versus sitagliptin (4 vs. 1 event, p=0.2) . Only 70% of sitagliptin orders were appropriately dosed based on eGFR. Conclusion: There was no difference between linagliptin and sitagliptin in regards to mean daily BG and cardiovascular outcomes. However, there were numerically more BG readings within range with linagliptin. Our results favor the utilization of linagliptin in the inpatient setting considering it does not require renal dose adjustments. Disclosure S. Barakat: None. H. A. Habib: None. C. Chun: None. E. Oh: None.

Abstract 40: Comparative Effectiveness Of Sglt2 And Glp1ra On Major Adverse Cardiac Events: A National Retrospective Cohort Of Patients With Diabetes

Background: To test the hypothesis that patients treated with sodium-glucose cotransporter 2 (SGLT2) inhibitors or glucagon-like peptide 1 receptor agonists (GLP1RA) was associated with lower risk of cardiovascular endpoints vs dipeptidyl peptidase 4 inhibitors (DPP4). Methods: A retrospective cohort combined Veterans Administration, Medicare, and National Death Index databases. Patients using metformin, sulfonylurea or insulin alone or in combination were followed until a new fill of one of the following classes: SGLT2; GLP1RA; or DPP4. The index date and start of follow-up was the new prescription fill date. The composite outcome was major adverse cardiovascular event (MACE) or heart failure (HF) hospitalization: acute myocardial infarction (AMI), stroke, acute HF or cardiovascular (CV) death. Cox Proportional Hazards models compared MACE and HF for the comparison groups of interest, separately, in propensity score (PS) weighted cohorts adjusted for clinical covariates, laboratory data, ejection fraction (EF), smoking, and selected medications. Results: After PS weighting the cohorts included 46018 GLP1RA vs 45814 DPP4 and 36646 SGLT2 vs 36261 DPP4 participants. Median age was 69 years and diabetes duration of 9.0 (5.2, 13.4) years for GLP1RA vs DPP4 and 9.3 (5.7, 13.8) years for SGLT2 vs DPP4 users. Most new agents were added as third drug to either metformin + sulfonylurea or metformin + insulin regimen. GLP1RA was associated with lower hazard of MACE/HF vs DPP4 (0.73 [0.68, 0.78]) (panel A) yielding an adjusted risk difference (aRD) of 10.5 events [8.5, 12.4]); results were consistent for all outcome components. SGLT2 was associated with a lower hazard of MACE and HF (0.76 [0.69, 0.85]) (panel B) (aRD 8.1 [5.2, 10.7]); primarily due to reduction in CV death (0.71 [0.56, 0.90]) and HF hospitalization with reduced EF (0.40 [0.26, 0.62]). Conclusions: Use of GLP1RA or SGLT2 for diabetes treatment was associated with reduced risk of MACE and HF hospitalization vs DPP4.

The Relationship Between Body Mass Index and In-hospital Survival in Patients Admitted With Acute Heart Failure.

BackgroundThe association between Body Mass Index (BMI) and clinical outcomes following acute heart failure (AHF) hospitalization is debated in the literature. Our objective was to study the real-world relationship between BMI and in-hospital mortality in patients who were admitted with AHF.MethodsIn this retrospective, multi-center study, we utilized the National Inpatient Sample (NIS) database to identify a sampled cohort of patients who were hospitalized with AHF between October 2015 and December 2016. Outcomes of interest included in-hospital mortality and length of stay (LOS). Patients were divided into 6 BMI (kg/m2) subgroups according to the World Health Organization (WHO) classification: (1) underweight ≤ 19, (2) normal weight 20–25, (3) overweight 26–30, (4) obese I 31–35, (5) obese II 36–39, and (6) extremely obese ≥40. A multivariable logistic regression model was used to identify predictors of in-hospital mortality and to identify predictors of LOS.ResultsA weighted total of 219,950 hospitalizations for AHF across the US were analyzed. The mean age was 66.3 ± 31.5 years and most patients (51.8%) were male. The crude data showed a non-linear complex relationship between BMI and AHF population outcomes. Patients with elevated BMI exhibited significantly lower in-hospital mortality compared to the underweight and normal weight study participants (5.5, 5,5, 2,8, 1.6, 1.4, 1.6% in groups by BMI ≤ 19, 20–25, 26–30, 31–35, 36–39, and, ≥40 respectively, p < 0.001) and shorter LOS. In the multivariable regression model, BMI subgroups of ≤ 25kg/m2 were found to be independent predictors of in-hospital mortality. Age and several comorbidities, and also the Deyo Comorbidity Index, were found to be independent predictors of increased mortality in the study population.ConclusionA reverse J-shaped relationship between BMI and mortality was documented in patients hospitalized for AHF in the recent years confirming the “obesity paradox” in the real-world setting.

Dapagliflozin Treatment Improves Cardiac Remodeling and Dysfunction in Heart Failure Induced Rats

Background: Sodium-glucose cotransporter-2 (SGLT-2) inhibitor dapagliflozin is a novel antihyperglycemic drug that has cardioprotective effects. It has been shown to minimize the incidence of cardiovascular mortality and heart failure (HF) hospitalization. Furthermore, these benefits may remain regardless of the existence of diabetes. However, the mechanisms by which dapagliflozin mediates these effects in HF patient are unknown, and its efficacy and practical use are still debatable. Objectives: to assess the therapeutic effect of dapagliflozin on rat with experimentally induced HF and its possible underlying mechanism of action. Methods: The left anterior descending (LAD) coronary artery was ligated in rats to induce HF. Dapagliflozin (1 mg/kg/day) was given by gavage for four weeks. Heart weight (HW), Body weight (BW), blood pressure, heart rate (HR), fasting serum glucose, insulin, glycated hemoglobin A1C (HbA1c), cardiac injury markers [creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), lactate dehydrogenase (LDH)], markers of fibrosis [transforming growth factor beta 1 (TGF-β1), procollagen I C-terminal propeptide (PICP), procollagen III N-terminal peptide (PIIINT)], mediators of inflamation [tumor necrosis factor-alpha (TNF-α)], markers of oxidative stress [super oxide dismutase (SOD) and malondialdehyde (MDA)] and mediators of apoptosis (caspase 3 and BCL-2) were assessed. Histopathological examinations were performed using hematoxylin and eosin (H &amp; E) for the heart, lung, and liver, and masson trichrome for heart. Results: Dapagliflozin decreased HW, HW/BW, cardiac injury markers, markers of fibrosis, mediators of inflammation, MDA and cardiac level of Caspase 3, while increased levels of SOD and BCL-2 in HF-induced rats. Dapagliflozin also improved the histopathological picture of heart, liver and lung. Conclusion: Dapagliflozin attenuated fibrosis, inflammation, oxidative stress, and apoptosis in HF-induced rats, thereby alleviating myocardial remodeling and dysfunction. Dapagliflozin alleviated histopathological changes in the hearts, lungs, and livers.

Different Renal Function Patterns in Patients With Acute Heart Failure: Relationship With Outcome and Congestion.

BackgroundThe role of worsening renal function during acute heart failure (AHF) hospitalization is still debated. Very few studies have extensively evaluated the renal function (RF) trend during hospitalization by repetitive measurements.ObjectivesTo investigate the prognostic relevance of different RF trajectories together with the congestion status in hospitalized patients.MethodsThis is a post hoc analysis of a multi-center study including 467 patients admitted with AHF who were screened for the Diur-AHF Trial. We recognized five main RF trajectories based on serum creatinine and estimated glomerular filtration rate (eGFR) behavior. According to the RF trajectories our sample was divided into 1-stable (S), 2-transient improvement (TI), 3-permanent improvement (PI), 4-transient worsening (TW), and 5-persistent worsening (PW). The primary outcome was the combined endpoint of 180 days including all causes of mortality and re-hospitalization.ResultsWe recruited 467 subjects with a mean congestion score of 3.5±1.08 and a median creatinine value of 1.28 (1.00–1.70) mg/dl, eGFR 50 (37–65) ml/min/m2 and NTpro B-type natriuretic peptide (BNP) 7,000 (4,200–11,700) pg/ml. A univariate analysis of the RF pattern demonstrated that TI and PW patterns were significantly related to poor prognosis [HR: 2.71 (1.81–4.05); p < 0.001; HR: 1.68 (1.15–2.45); p = 0.007, respectively]. Conversely, the TW pattern showed a significantly protective effect on outcome [HR:0.34 (0.19–0.60); p < 0.001]. Persistence of congestion and BNP reduction ≥ 30% were significantly related to clinical outcome at univariate analysis [HR: 2.41 (1.81–3.21); p < 0.001 and HR:0.47 (0.35–0.67); p < 0.001]. A multivariable analysis confirmed the independently prognostic role of TI, PW patterns, persistence of congestion, and reduced BNP decrease at discharge.ConclusionsVarious RF patterns during AHF hospitalization are associated with different risk(s). PW and TI appear to be the two trajectories related to worse outcome. Current findings confirm the importance of RF evaluation during and after hospitalization.

COVID-19 in China and the US: Differences in Hospital Admission Co-Variates and Outcomes.

(1) Background: Although there are extensive data on admission co-variates and outcomes of persons with coronavirus infectious disease-2019 (COVID-19) at diverse geographic sites, there are few, if any, subject-level comparisons between sites in regions and countries. We investigated differences in hospital admission co-variates and outcomes of hospitalized people with COVID-19 between Wuhan City, China and the New York City region, USA. (2) Methods: We retrospectively analyzed clinical data on 1859 hospitalized subjects with COVID-19 in Wuhan City, China, from 20 January to 4 April 2020. Data on 5700 hospitalized subjects with COVID-19 in the New York City region, USA, from 1 March to 4 April 2020 were extracted from an article by Richardson et al. Hospital admission co-variates (epidemiological, demographic, and laboratory co-variates) and outcomes (rate of intensive care unit [ICU] admission, invasive mechanical ventilation [IMV], major organ failure and death, and length of hospital stay) were compared between the cohorts. (3) Results: Wuhan subjects were younger, more likely female, less likely to have co-morbidities and fever, more likely to have a blood lymphocyte concentration > 1 × 109/L, and less likely to have abnormal liver and cardiac function tests compared with New York subjects. There were outcomes data on all Wuhan subjects and 2634 New York subjects. Wuhan subjects had higher blood nadir median lymphocyte concentrations and longer hospitalizations, and were less likely to receive IMV, ICU hospitalization, and interventions for kidney failure. Amongst subjects not receiving IMV, those in Wuhan were less likely to die compared with New York subjects. In contrast, risk of death was similar in subjects receiving IMV at both sites. (4) Conclusions: We found different hospital admission co-variates and outcomes between hospitalized persons with COVID-19 between Wuhan City and the New York region, which should be useful developing a comprehensive global understanding of the SARS-CoV-2 pandemic and COVID-19.

Outcomes of patients with severe mitral regurgitation treated with transcatheter mitral valve implantation or medical therapy

Abstract Funding Acknowledgements Type of funding sources: None. Background Patients with severe mitral regurgitation (MR) unsuitable for standard therapy (i.e., open-heart surgery and transcatheter edge-to-edge repair [TEER]), often remain on medical therapy (MT) alone. Transcatheter mitral valve implantation (TMVI) may represent an alternative treatment option for these patients. Purpose We aimed to investigate differences in anatomical baseline characteristics and echocardiographic outcomes between MR patients unsuitable for standard therapy, that were either treated with TMVI or remained on MT. Methods Between 05/2016-02/2021, 121 high-risk patients with severe MR were evaluated for TMVI. Clinical, echocardiographic and functional outcomes between the subgroups of patients treated with TMVI and MT were compared. The primary combined endpoint was all-cause death or heart failure (HF) hospitalization at 1 year. Subgroup analyses were performed to define specific patient subsets favouring either TMVI or MT. Results At baseline, there were no differences between the TMVI group (n = 38) and the MT group (n = 44) regarding age (all TMVI vs. MT: 77.0 years [IQR 72.9, 80.1] vs. 79.0 [IQR 76.0, 81.7], p = 0.13), gender (42.1% female vs. 56.8% female, p = 0.27) and estimated surgical risk (EuroSCORE II 4.4% [IQR 2.8, 13.6] vs. 6.4 [IQR 3.4, 10.1], p = 0.72). Patients undergoing TMVI were more frequently treated for secondary MR (68.4%), while primary MR was the most prevalent MR etiology in patients remaining on medical therapy (50.0%). Left ventricular (LV) end-diastolic diameters (LVEDD) were larger and LV ejection fraction (LVEF) was lower in the TMVI group (LVEDD 58.0mm [IQR 51.4, 65.0], LVEF 37.0% [IQR 31.4, 51.2]) compared to the MT group (LVEDD 52.0mm [IQR 46.2, 58.8], LVEF 54.5% [IQR 40.8, 60.0]) (p = 0.02 for LVEDD, p &amp;lt; 0.001 for LVEF). MR was effectively reduced to ≤ mild MR in all patients undergoing TMVI. In the MT group, MR remained severe in 90% of patients after 1 year. The primary composite endpoint occurred numerically more often in the MT group (72.2%) compared to the TMVI group (51.6%, p = 0.061). Regarding the primary endpoint, the subgroups of patients with LVEF 30-49% (HR 0.28 [95%-CI 0.11-0.67], p = 0.004), effective regurgitant orifice area (EROA) &amp;lt;0.4 cm2 (HR 0.30 [95%-CI 0.13-0.71], p = 0.006), tricuspid annular plane systolic excursion (TAPSE) ≥17mm (HR 0.27 [95%-CI 0.11-0.67], p = 0.005) and New York Heart Association functional class III (HR 0.38 [95%-CI 0.18-0.81], p = 0.012) were more likely to benefit from TMVI compared to MT. Conclusions In patients with severe MR unsuitable for standard therapy, TMVI represents a reasonable therapeutic alternative yielding effective elimination of MR. While most patients eligible for TMVI suffer from secondary MR, the majority of patients remaining on MT has primary MR. The primary endpoint occurred numerically, yet not statistically, more often in patients on MT. Baseline echocardiography was able to identify subgroups of patients with beneficial outcome after TMVI.

Prognostic Implications of Right Atrial Dysfunction in Adults With Pulmonary Atresia and Intact Ventricular Septum.

Pulmonary atresia with intact ventricular septum is associated with significant morbidity and mortality, but there are limited data to guide risk stratification in this population. The purpose of this study was to assess the role right atrial (RA) strain indices for prognostication in this population. This is a retrospective study of adults (aged ≥18 years) with pulmonary atresia with intact ventricular septum and biventricular repair who underwent echocardiogram (2003-2019). RA reservoir strain was used as the primary metric of RA function, and RA dysfunction was defined as RA reservoir strain <31%. Clinical outcomes were assessed using 4 different indices: (1) functional impairment (New York Heart Association II-IV); (2) hepatorenal dysfunction (model for end-stage liver disease excluding international normalized ratio score >11); (3) incident atrial arrhythmias/heart failure hospitalization; (4) heart transplant/cardiovascular death. Of the 43 patients in the study, RA strain imaging was feasible in 95%, and RA dysfunction was present in 95%. Of the 43 patients, 67% and 49% had functional impairment and hepatorenal dysfunction, respectively; 44% developed incident atrial arrhythmia/heart failure hospitalization and 14% died during follow-up. RA reservoir strain was independently associated with all indices of clinical outcomes. Collectively, these data suggest that RA strain imaging was feasible in almost all patients and can be used for risk stratification in this population. There was a high prevalence of comorbidities including hepatorenal dysfunction. Further studies are needed to determine the prognostic implications of hepatorenal dysfunction (a previously unrecognized complication), and whether using RA function indices for clinical decision making will lead to improved outcomes in this population.

84 Left atrial reverse remodelling in dilated cardiomyopathy

Abstract Aims Left atrial (LA) dilation is associated a with worse prognosis in several cardiovascular settings but therapies can promote LA reverse remodelling. Characterizing and defining the prognostic implications of LA volume (LAVI) reduction in dilated cardiomyopathy (DCM). Methods and results Consecutive DCM patients from two tertiary care centres, with available echocardiography at baseline and at 1 year follow-up, were analysed. LA dilation was defined as LAVI &amp;gt;34 ml/m2, Delta (Δ)LAVI was defined as the 1 year relative LAVI reduction. The outcome was a composite of death/heart transplantation/heart failure hospitalization (D/HTx/HFH). Five hundred sixty patients were included [age 52 ± 13 years; left ventricular ejection fraction (LVEF) 31 ± 10%, LAVI 45 ± 18 ml/m2]. Baseline LAVI had a non-linear association with the risk of D/HTx/HFH, independently from LVEF (P &amp;lt; 0.001). At 1 year follow-up, LAVI decreased in 374 patients (67%, median ΔLAVI 24%, interquartile range 37% 11%). Factors independently associated with ΔLAVI were higher baseline LAVI and lower baseline LVEF. After adjustment for confounders, ΔLAVI showed a linear association with the risk of D/HTx/HHF (HR: 0.92, 95% CI: 0.86 0.99 per 5% decrease, P &amp;lt; 0.001). At 1 year Follow-up, patients with a ≥ 15% reduction in ΔLAVI or LAVI normalization (i.e. Follow-up LAVI ≤34ml/m2) (42% of the cohort) were at lower risk of D/HTx/HFH (HR: 0.49, 95% CI: 0.33 0.74, P &amp;lt; 0.001). Conclusions In a large cohort of DCM, 1 year reduction in LAVI is observed in the majority of patients. The association between reduction in LAVI and D/HTx/HHF candidates LA reverse remodelling as complementary early therapeutic goal in DCM.

Mortality and Readmission Rates After Heart Failure: A Systematic Review and Meta-Analysis.

ObjectiveThe current work aimed to examine the rates of and risk factors for mortality and readmission after heart failure (HF).SettingA systematic search was carried out in PubMed, the Cochrane Library, and EMBASE to identify eligible reports. The random-effects model was utilized to evaluate the pooled results.ParticipantsA total of 27 studies with 515,238 participants were finally meta-analysed. The HF patients had an average age of 76.3 years, with 51% of the sample being male, in the pooled analysis.Primary and Secondary Outcome MeasuresThe outcome measures were 30-day and 1-year readmission rates, mortality, and risk factors for readmission and mortality.ResultsThe effect sizes for readmission and mortality were estimated as the mean and 95% confidence interval (CI). The estimated 30-day and 1-year all-cause readmission rates were 0.19 (95% CI 0.14–0.23) and 0.53 (95% CI 0.46–0.59), respectively, while the all-cause mortality rates were 0.14 (95% CI 0.10–0.18) and 0.29 (95% CI 0.25–0.33), respectively. Comorbidities were highly prevalent in individuals with HF.ConclusionHeart failure hospitalization is followed by high readmission and mortality rates.