Prior Heart Failure Hospitalization Research Articles

Initiation and continuation of pharmacological therapies in patients hospitalized for heart failure in Japan.

Currently, the utilization patterns of medications for heart failure (HF) after worsening HF events remain unelucidated in Japan. Here, we conducted a retrospective cohort study evaluating the changes in HF drug utilization patterns in 6 months before and after hospitalizations for HF. The adherence to newly initiated HF medications was evaluated based on the proportion of days covered (PDC) and persistence as continuous treatment episodes among new users. The study included 9091 patients hospitalized for HF between January 2016 and September 2019, including 2735 (30.1%) patients who were newly prescribed at least one HF medication after hospitalization. Despite increases in the use of foundational HF therapy (beta-blockers, angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers, or mineralocorticoid receptor antagonists), 35.6% and 7.6% of patients were treated with the HF foundational monotherapy or diuretics alone after hospitalization, respectively. The mean PDC of newly initiated HF medications ranged from 0.57 for thiazide diuretics to 0.77 for sodium-glucose cotransporter-2 inhibitors. Continuous use of HF medications during the first year after initiation was observed in 30-60% of patients. The mean PDC and one-year continuous HF medication use were consistently lower in patients aged ≥ 75years and in patients with a history of HF hospitalization for all HF medication classes except for tolvaptan and digoxin. Despite the guideline recommendations of HF pharmacotherapy, both treatment and adherence were suboptimal after HF hospitalization, especially in vulnerable populations such as older patients and those with prior HF hospitalizations.

Dapagliflozin and Timing of Prior HeartFailure Hospitalization: A Patient-Level Meta-Analysis of DAPA-HF and DELIVER.

Patients recently hospitalized for heart failure (HF) are at a higher risk of adverse clinical outcomes, but they may experience a greater absolute and relative benefit from effective therapies than individuals who are considered more "stable." The authors examined the effects of dapagliflozin according to the timing of prior HF hospitalization in a patient-level pooled analysis of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure). A total of 11,007 patients were randomized in DAPA-HF and DELIVER. The primary outcome was the composite of worsening HF or cardiovascular death. In total, 12.4% were hospitalized for HF within 3months of randomization, 14.2% between 3 and 12months, and 16.8% more than 1 year before randomization, whereas 56.5% had not been hospitalized. The risk of the primary endpoint was inversely associated with time from prior HF hospitalization, and patients with a recent HF hospitalization had the highest risk. Compared with placebo, dapagliflozin reduced the risk of the primary outcome across HF hospitalization category (0-3months, HR: 0.66 [95%CI: 0.55-0.81]; 3-12months, HR: 0.73 [95%CI: 0.59-0.90]; >1year, HR: 0.91 [95%CI: 0.74-1.12]; and no prior hospitalization, HR: 0.83 [95%CI: 0.73-0.94]; Pinteraction=0.09). The number of patients needed to treat with dapagliflozin to prevent 1 event over the median follow-up of 22months was 13, 20, 23, and 28, respectively. The beneficial effect was consistent across the range of LVEF regardless of HF hospitalization category. The relative benefits of dapagliflozin were consistent across the range of LVEF regardless of the timing of the most recent HF hospitalization with a greater absolute benefit in patients with recent hospitalization.

Twelve-month follow-up results from the SIRONA 2 clinical trial.

In the SIRONA 2 trial, the safety and efficacy of pulmonary artery (PA) pressure (PAP)-guided heart failure (HF) management using a novel PAP sensor were assessed at 30 and 90days, respectively, and both endpoints were met. The current study examines the prespecified secondary endpoints of safety and accuracy of the PA sensor along with HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance through 12months. SIRONA 2 is a prospective, multi-centre, open-label, single-arm trial evaluating the Cordella™ PA Sensor System in 70 patients with New York Heart Association (NYHA) functional class III HF with a prior HF hospitalization and/or increase of N-terminal pro-brain natriuretic peptide within 12months of enrolment. Sensor accuracy was assessed and compared with measurements obtained by standard right heart catheterization (RHC). Safety was defined as freedom from prespecified adverse events associated with use of the Cordella PA Sensor System and was assessed in all patients who entered the cath lab for PA sensor implant. HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance were also assessed. At 12months, there was good agreement between the Cordella PA Sensor System and RHC, with the average difference for mean PAP being 2.9±7.3mmHg. The device safety profile was excellent with 98.4% freedom from device/system-related complications. There were no pressure sensor failures. HF hospitalizations and mortality were low with a rate of 0.33 event per patient year. Symptoms as assessed by NYHA (P<0.0001) and functional capacity as measured by 6min walk test (P=0.02) were significantly improved. Patients' adherence to daily transmissions of PAP and vital signs measurements was 95%. Long-term follow-up of the SIRONA 2 trial supports the safety and accuracy of the Cordella PA Sensor System in enabling comprehensive HF management in NYHA class III HF patients.

Pregnancy and cardiac maternal outcomes in women with inherited cardiomyopathy: interest of the new CARPREG II risk score

Abstract Introduction Inherited cardiomyopathies are rare but at high risk of cardiac maternal morbidity and mortality during pregnancy and post-partum. However data for risk stratification remains scarce. The new CARPREG II index score emerged to better predict prognosis in pregnancies with heart disease. Still, role of this score in inherited cardiomyopathies is unclear. Objective To describe characteristics and cardiac maternal outcomes in patients with inherited cardiomyopathy during pregnancy, and to evaluate the interest of the various index scores in this population. Methods In this retrospective monocentric study, 90 pregnancies of 74 patients were included (mean age 32 ± 5 years), with 28 dilated cardiomyopathies (DCM), 46 hypertrophic cardiomyopathies, 11 arrhythmogenic right ventricular cardiomyopathies and 5 left ventricular non compaction, excluding peri partum cardiomyopathies. Results A cardiac maternal complication was observed for 18 (20%) pregnancies, mainly driven by arrythmia and heart failure, and with 3 cardiovascular deaths. 43 (48 %) presented fetal or neo natal complications, with 18 premature delivery and 3 fetal or neonatal death. Median CARPREG II score was 2 [0;3], higher in the DCM subgroup. CARPREG II was significantly associated with the onset of cardiac maternal complication (p&amp;lt; 0.05 for all) and seemed to show a better performance for risk stratification than previous scores (Area under curve of ROC: 0.782 for CARPREG II, AUC 0.755 and 0.697 for CARPREG and mWHO respectively). Prior hospitalization for heart failure, left ventricular dysfunction, multiple line treatments, cardiac symptoms prior to pregnancy and late pregnancy assessment were associated with cardiac complications (p &amp;lt; 0.05 for all) Conclusion Pregnancy in women with inherited cardiomyopathy remains at high risk of maternal cardiovascular major events. Late pregnancy assessment and initial severity of cardiomyopathy were found associated with cardiac prognosis. The new CARPREG II score appeared as the most efficient for cardiac risk stratification in this population.

Effects of dapagliflozin in heart failure with preserved ejection fraction and chronic obstructive pulmonary disease: an analysis of the DELIVER trial

Abstract Introduction Chronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure (HF) with preserved ejection fraction (HFpEF) and associated with worse outcomes. Purpose We investigated the relationship between COPD status and outcomes, and the efficacy of dapagliflozin, compared with placebo, according to COPD status in patients with heart failure (HF) with preserved ejection fraction (HFpEF) randomized in DELIVER. Methods A total of 6,263 patients with HF with New York Heart Association functional class II-IV, left ventricular ejection fraction &amp;gt;40%, evidence of structural heart disease, and elevated N-terminal pro–B-type natriuretic peptide levels were randomized to dapagliflozin or placebo. Clinical outcomes and the effect of dapagliflozin, according to COPD status at baseline, were examined. The primary outcome was a composite of cardiovascular death or worsening HF. Results Of the 6,261 patients with data on baseline COPD, 692 (11.1%) had a history of COPD. Compared with patients without COPD, those with COPD were older, more often men and current smokers, and they had a higher BMI, but lower systolic blood pressure. Patients with COPD also had a longer duration of HF, a higher rate of prior HF hospitalization, higher NT-proBNP, and worse NYHA functional class and KCCQ-TSS. The risk of the primary endpoint was higher in patients with COPD compared with those without COPD (adjusted HR: 1.29 (95% CI: 1.09-1.52). The benefit of dapagliflozin on the primary outcome was consistent irrespective of COPD status: no COPD, HR: 0.82 (95% CI: 0.72-0.93); COPD, HR: 0.84 (95% CI: 0.63-1.12) (Pinteraction = 0.92). Consistent effects were observed for HF hospitalization, cardiovascular death, and all-cause mortality (Table). Dapagliflozin, as compared with placebo, increased (improved) the KCCQ-TSS from baseline to 8 months to a similar extent in patients with and without COPD (Pinteraction = 0.75) (Table). Adverse events and treatment discontinuation were not more frequent with dapagliflozin than with placebo irrespective of COPD status. Conclusions COPD is common in patients with HFpEF and associated with worse outcomes. Dapagliflozin reduced the risk of worsening HF or cardiovascular death, and improved symptoms, similarly in patients with and without COPD. In addition, dapagliflozin was safe and well-tolerated, irrespective of COPD status.

Abstract 13820: Association of Cardiothoracic Ratio With Heart Failure Events in Atrial Fibrillation Without Heart Failure: The Fushimi AF Registry

Background: The cardiothoracic ratio (CTR) is a readily available and non-invasive tool with which to assess cardiac volume status. We previously reported that N-terminal pro-B-type natriuretic peptide (NT-proBNP) level was associated with higher incidence of clinical events in patients with atrial fibrillation (AF) without pre-existing heart failure (HF). However, it remains unknown whether CTR on chest radiography is associated with the incidence of HF events in AF patients without HF. Methods: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. After excluding patients with pre-existing HF (defined as having one of the following; prior HF hospitalization, New York Heart Association class ≥2, or left ventricular ejection fraction &lt;40%), we divided 1,049 patients into four groups according to their CTR and NT-proBNP level (median value: 495 ng/L) at baseline, and compared the incidence of HF events (composite of cardiac death or HF hospitalization) among the groups; G1 (Lower CTR&lt;50% and Lower NT-proBNP&lt;495, n=256), G2 (Higher CTR≥50% and Lower NT-proBNP&lt;495, n=268), G3 (Lower CTR&lt;50% and Higher NT-proBNP≥495, n=117) and G4 (Higher CTR≥50% and Higher NT-proBNP≥495, n=408). Results: During the median follow-up of 5.4 years, the incidence rates of HF events in the groups either having higher NT-pro BNP group or higher CTR group were higher, as compared with patients with lower CTR and lower NT-proBNP (G1: 0.5% per person-year, G2: 1.3%, G3: 1.6% and G4: 2.5%; p&lt;0.01) (Figure). Multivariate Cox regression analysis revealed that higher CTR (≥50%) was independently associated with the incidence of HF events in AF patients without prior HF hospitalization (hazard ratio: 1.47, 95% confidence interval: 1.09-2.00). Conclusion: In Japanese AF patients without pre-existing HF, higher CTR was associated with higher incidence of HF events irrespective of NT-proBNP level.

Abstract 12840: Left Atrial Enlargement is a Useful Predictor for Incident Heart Failure in Atrial Fibrillation Patients Without Pre-Existing Heart Failure

Background: Atrial fibrillation (AF) increases the risk of heart failure (HF). However, little focus has been placed on the risk stratification for HF in AF patients. Hypothesis: Left atrial diameter (LAD) is a simple prognostic parameter in patients with HF. We hypothesized that LAD is a useful predictor for incident HF in AF patients even without pre-existing HF. Methods: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Japan. After excluding patients with pre-existing HF (defined as having one of the following; prior HF hospitalization, New York Heart Association class ≥2, or left ventricular ejection fraction &lt;40%), we investigated 2,464 patients with the data of LAD at enrollment. We divided the patients into 4 groups stratified by LAD (&lt;40 mm, 40-44 mm, 45-49 mm, and ≥50 mm), and compared the backgrounds and incidence of HF hospitalization between the groups. Results: Of 2,464 patients (mean age: 72±11 years, female: 919 [37%], paroxysmal AF: 1,405 [57%], and mean CHA2DS2-VASc score: 3.0±1.6), the mean LAD was 42±8 mm (&lt;40 mm: 1007 [41%], 40-44 mm: 650 [26%], 45-49 mm: 467 [19%] and ≥50 mm: 340 [14%], respectively). Patients with larger LAD had a higher prevalence of elderly and non-paroxysmal AF, and had a higher CHA2DS2-VASc score (all P&lt;0.001). During the median follow-up of 6.0 years, 260 patients (11%) were hospitalized for HF (annual incidence: 1.8% per person-year). Kaplan-Meier curves revealed that LAD was able to stratify the incidence of HF hospitalization in AF patients without HF (Figure). Multivariable Cox regression analysis demonstrated that larger LAD were independently associated with the risk of HF after adjustment by age, sex, AF type, and CHA2DS2-VASc score (Figure). Conclusion: Larger LAD was significantly associated with the higher incidence of HF hospitalization in AF without pre-existing HF, suggesting the utility of LAD regarding the risk stratification for HF in these patients.

Abstract 13563: Long-Term Prognostic Value of Afterload Mismatch Index in Acute Decompensated Heart Failure With and Without Reduced Left Ventricular Ejection Fraction

Backgrounds: Ventricular-arterial coupling has been shown to have physiologic importance in heart failure. At the acute worsening of heart failure, increased ratio of pulmonary capillary wedge pressure to systemic systolic pressure (PCWP/SBP) might reflect the degree of afterload mismatch. However, there is no information available on the long-term prognostic value of PCWP/SBP in patients with acute decompensated heart failure (ADHF), relating to reduced left ventricular ejection fraction (LVEF). Methods: We studied 240 patients admitted for ADHF (with LVEF&lt;40% [HFrEF, n=110] and without LVEF&lt;40% [n=130]), who underwent right heart catheterization at the admission and were discharged with survival. PCWP/SBP was obtained at the admission. The study endpoint was cardiovascular death (CVD). Results: During a mean follow-up period of 5.2±4.4 yrs, 59 patients had CVD. PCWP/SBP was significantly higher in patients with than without CVD (0.216±0.078 vs 0.172±0.064, p&lt;0.0001). Multivariate Cox regression analysis revealed that PCWP/SBP was significantly associated with CVD, independently of prior heart failure hospitalization, body mass index, estimated glomerular filtration rate, and serum sodium level. Patients with high PCWP/SBP (&gt;0.206 determined by ROC analysis: AUC 0.668[0.586-0.749]) had a significantly greater CVD risk than those with low PCWP/SBP (≤0.206) in both groups with and without HFrEF(with: 36% vs 11%, p=0.016; without: 42% vs 18%, p=0.0057). Conclusions: PCWP/SBP, an index of afterload mismatch, could provide the long-term prognostic information in patients admitted with ADHF, regardless of reduced LVEF.

Abstract 13565: Long-Term Prognostic Value of the Combination of Systemic Immune-Inflammation Index and AHEAD Score and in Patients Admitted for Acute Decompensated Heart Failure

Backgrounds: Systemic inflammation plays a critical role in the outcomes of heart failure patients. A newly defined index, which is named as systemic immune-inflammation index (SII), had been reported to have prognostic value in patients with cardiovascular disease. On the other hand, comorbidities are strongly associated with poor clinical outcome in heart failure patients (pts). AHEAD (A: atrial fibrillation; H: hemoglobin; E: elderly; A: abnormal renal parameters; D: diabetes mellitus) score was known to be related to clinical outcomes in acute decompensated heart failure (ADHF) patients. We sought to investigate the prognostic value of the combination of SII and AHEAD in patients admitted for ADHF. Methods and Results: We studied 263 patients admitted for ADHF and discharged with survival. At the discharge, we obtained SII, which is computed as neutrophils x platelets / lymphocytes, and AHEAD score (range 0-5, atrial fibrillation, hemoglobin &lt;13 mg/dL for men and 12 mg/dL for women, age &gt;70 years, creatinine &gt;130 μmol/L, and diabetes mellitus). During a follow-up period of 5.0±4.2 yrs, 67 patients had cardiovascular death (CVD). At multivariate Cox analysis, SII and AHEAD score were significantly independently associated with CVD, independently of prior heart failure hospitalization, systolic blood pressure and left ventricular dimension index. The patients with both greater SII (≥571 determined by ROC analysis: AUC 0.632[0.553-0.712]) and AHEAD score (≥3: AUC 0.635[0.562-0.707]) had a significantly increased risk of CVD than those with either and none of them (51% vs 28% vs 16%, p&lt;0.0001, respectively). Conclusion: The combination of SII and AHEAD score would be useful for stratifying patients at risk for cardiovascular-renal poor outcome in ADHF patients.

Abstract 13552: Prognostic Value of Modified Body Mass Index in Acute Decompensated Heart Failure Patients With Reduced, Mildly-Reduced and Preserved Left Ventricular Ejection Fraction

Backgrounds: Malnutrition is associated with poor outcome in patients with acute decompensated heart failure (ADHF). Although conventional body mass index (cBMI) and serum albumin level are commonly used as indicators of malnutrition, these variables are influenced by fluid balance, and it has been recently reported that the modified BMI (mBMI, serum albumin х cBMI) would be a better prognostic marker than cBMI and serum albumin level in ADHF patients. However, it remains unclear whether mBMI on admission or discharge would have more prognostic information in patients admitted with ADHF after the discharge, and there is no information available on the prognostic impact of mBMI in ADHF patients, relating to reduced (HFrEF), mildly-reduced (HFmrEF), and preserved left ventricular ejection fraction (HFpEF). Methods and Results: We studied 263 ADHF patients (HFrEF:n=103, HFmrEF:n=59, HFpEF:n=101) discharged with survival. We calculated mBMI on admission and discharge. During a follow up period of 5.1±4.3 yrs, 67 patients had cardiovascular death (CVD). AUC of mBMI at discharge (0.697[0.625-0.769]) was greater than that on admission (0.661[0.585-0.737], p=0.055). At multivariate Cox analysis, mBMI at discharge (adjusted hazard ratio 0.965[0.948-0.982], p&lt;0.001) was significantly associated with CVD, independently of prior heart failure hospitalization, systolic blood pressure, eGFR and serum sodium level. Patients with lower mBMI (&lt;median value=75.4) had an increased risk of CVD than those with higher mBMI (≥75.4) in all three subgroups (HFrEF: 43% vs 21%, p=0.013, HFmrEF; 32% vs 11%, p=0.025, HFpEF: 41% vs 12%, p=0.008). Conclusion: Modified BMI at the discharge might be better prognostic marker than that on admission and provides long-term prognostic information in patients admitted for ADHF, regardless of reduced, mildly-reduced or preserved left ventricular ejection fraction.

High-Dose vs. Standard-Dose Influenza Vaccine and Cardiopulmonary Hospitalization or Mortality: Emulating the INVESTED Trial Using Insurance Claims Data.

The INVESTED trial did not show benefits of high-dose (HD) vaccine vs. standard-dose (SD) for a primary composite outcome of cardiopulmonary hospitalization or all-cause mortality (hazard ratio (HR) = 1.05, 95% confidence interval (CI) = 0.96-1.15) and its components (all-cause mortality HR = 1.01, 95% CI = 0.84-1.21, cardiopulmonary hospitalization HR = 1.05, 95% CI = 0.96-1.16) during three influenza seasons (2016-2019) among participants with recent myocardial infarction or hospitalization for heart failure (HHF). We emulated INVESTED using Medicare claims data to assess whether the real-world evidence (RWE) study reached similar conclusions. We identified 1:1 propensity score (PS)-matched trial-eligible Medicare beneficiaries aged > 65 years and with prior HHF who received an HD or SD vaccine for the 2016-2019 seasons. We also re-analyzed the INVESTED trial data restricting to participants > 65 years with prior HHF to align eligibility criteria more closely with the RWE study. We compared HRs from the trial and RWE study for the main outcomes. Among 53,393 pairs of PS-matched Medicare beneficiaries, the HD vaccine group showed lower risk of the primary composite outcome (HR = 0.96, 95% CI = 0.95-0.98) and all-cause mortality (HR = 0.93, 95% CI = 0.91-0.95), and similar risk of cardiopulmonary hospitalization (HR = 0.98, 95% CI = 0.96-1.00), compared with SD. The RWE and trial results were closely concordant after the trial population was limited to participants > 65 years with prior HHF: trial-based results for the primary composite outcome (HR = 1.02, 95% CI = 0.89-1.17), all-cause mortality (HR = 0.92, 95% CI = 0.72-1.16), and cardiopulmonary hospitalization (HR = 1.02, 95% CI = 0.88-1.18). Although similar to the main trial results, the RWE was closer to the results from trial participants with aligned eligibility criteria. This study affirms the importance of considering different distributions of baseline patient characteristics when comparing trial findings to RWE.

Personalized lifetime prediction of survival and treatment benefit in patients with heart failure with reduced ejection fraction: The LIFE-HF model.

Although trials have proven the group-level effectiveness of various therapies for heart failure with reduced ejection fraction (HFrEF), important differences in absolute effectiveness exist between individuals. We developed and validated the LIFEtime-perspective for Heart Failure (LIFE-HF) model for the prediction of individual (lifetime) risk and treatment benefit in patients with HFrEF. Cox proportional hazards functions with age as the time scale were developed in the PARADIGM-HF and ATMOSPHERE trials (n = 15 415). Outcomes were cardiovascular death, heart failure (HF) hospitalization or cardiovascular death, and non-cardiovascular mortality. Predictors were age, sex, New York Heart Association class, prior HF hospitalization, diabetes mellitus, extracardiac vascular disease, systolic blood pressure, left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, and glomerular filtration rate. The functions were combined in life-tables to predict individual overall and HF hospitalization-free survival. External validation was performed in the SwedeHF registry, ASIAN-HF registry, and DAPA-HF trial (n = 51 286). Calibration of 2- to 10-year risk was adequate, and c-statistics were 0.65-0.74. An interactive tool was developed combining the model with hazard ratios from trials to allow estimation of an individual's (lifetime) risk and treatment benefit in clinical practice. Applying the tool to the development cohort, combined treatment with a mineralocorticoid receptor antagonist, sodium-glucose cotransporter 2 inhibitor, and angiotensin receptor-neprilysin inhibitor was estimated to afford a median of 2.5 (interquartile range [IQR] 1.7-3.7) and 3.7 (IQR 2.4-5.5) additional years of overall and HF hospitalization-free survival, respectively. The LIFE-HF model enables estimation of lifelong overall and HF hospitalization-free survival, and (lifetime) treatment benefit for individual patients with HFrEF. It could serve as a tool to improve the management of HFrEF by facilitating personalized medicine and shared decision-making.

Utility of left ventricular ejection fraction in atrial fibrillation patients without pre-existing heart failure.

Atrial fibrillation (AF) increases the risk of heart failure (HF); however, little focus has been placed on the prevention of HF in patients with AF. Left ventricular ejection fraction (LVEF) is an established echocardiographic parameter in HF patients. We sought to investigate the association of LVEF with HF events in AF patients without pre-existing HF. The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Japan. In this analysis, we excluded patients with pre-existing HF (defined as having one of the following: prior HF hospitalization, New York Heart Association class≥2 in association with heart disease, or LVEF<40%). Among 3233 AF patients without pre-existing HF, we investigated 2459 patients with the data of LVEF at enrolment. We divided the patients into three groups stratified by LVEF [mildly reduced LVEF (40-49%), below normal LVEF (50-59%), and normal LVEF (≥60%)] and compared the backgrounds and incidence of HF hospitalization between the groups. Of 2459 patients [mean age: 72.4±10.5years, female: 917 (37%), paroxysmal AF: 1405 (57%), and mean CHA2 DS2 -VASc score: 3.0±1.6], the mean LVEF was 66±8% [mildly reduced LVEF: 114 patients (5%), below normal LVEF: 300 patients (12%), and normal LVEF: 2045 patients (83%)]. Patients with lower LVEF demonstrated lower prevalence of female and paroxysmal AF (both P<0.01), but age and CHA2 DS2 -VASc score were comparable between the three groups (both P>0.05). During the median follow-up period of 6.0years, 255 patients (10%) were hospitalized for HF (annual incidence: 1.9% per person-year). Multivariable Cox regression analysis demonstrated that lower LVEF strata were independently associated with the risk of HF [mildly reduced LVEF (40-49%): hazard ratio=2.98, 95% confidence interval=1.99-4.45 and below normal LVEF (50-59%): hazard ratio=2.01, 95% confidence interval=1.44-2.82, compared with normal LVEF (≥60%)] after adjustment by age, sex, type of AF, and CHA2 DS2 -VASc score. LVEF<60% was significantly associated with the higher risk of HF hospitalization across all major subgroups without significant interaction (P for interaction; all P>0.05). LVEF had an independent and incremental prognostic value for HF hospitalization in addition to natriuretic peptide levels in AF patients without pre-existing HF. Lower LVEF was significantly associated with the higher incidence of HF hospitalization in AF patients without pre-existing HF, leading to the future risk stratification for and prevention of incident HF in AF patients.

Eligibility for vericiguat in a real-world heart failure population according to trial, guideline and label criteria: Data from the Swedish Heart Failure Registry.

We investigated the eligibility for vericiguat in a real-world heart failure (HF) population based on trial, guideline and label criteria. From the Swedish HF registry, 23 573 patients with HF with reduced ejection fraction (HFrEF) enrolled between 2000 and 2018, with a HF duration ≥6 months, were considered. Eligibility for vericiguat was calculated based on criteria from (i) the Vericiguat Global Study in Subjects with Heart Failure and Reduced Ejection Fraction (VICTORIA) trial; (ii) European and American guidelines on HF; (iii) product labelling according to the Food and Drug Administration and European Medicines Agency. Estimated eligibility for vericiguat in the trial, guidelines, and label scenarios was 21.4%, 47.4%, and 47.4%, respectively. Prior HF hospitalization within 6 months was the criterion limiting eligibility the most in all scenarios (met by 49.1% of the population). In the trial scenario, other criteria meaningfully limiting eligibility were elevated N-terminal pro-B-type natriuretic peptide levels and nitrate use. In all scenarios, eligibility was higher among patients hospitalized for HF at baseline (44.3% vs. 21.4% [trial scenario] and 97.3% vs. 47.4% [guideline/label scenarios] for hospitalized vs. non-hospitalized patients). Overall, eligible patients were older, had more severe HF, more comorbidities, and consequently higher cardiovascular mortality and HF hospitalization rates compared with ineligible patients across all scenarios. In a large and contemporary real-world HFrEF cohort, we estimated that 21.4% of patients would be eligible for vericiguat according to the VICTORIA trial selection criteria, 47.4% based on guidelines and labelling. Eligibility for vericiguat translated into the selection of a population at high risk of morbidity/mortality.

188-LB: Association between Age at Diagnosis of Type 2 Diabetes and Hospitalization for Heart Failure (HHF)

Background: The relation between age at T2D diagnosis and HHF is unclear. We conducted a population-based cohort study to examine the association between age at diagnosis of T2D and incident HHF in Ontario, Canada. Methods: Using administrative health databases, we identified people with new-onset T2D between April 1, 2005 and March 31, 2015. We matched each person to 3 other people without diabetes according to birth year and sex. We excluded any people with prior HHF. We used Cox proportional hazards models to estimate adjusted hazard ratios (HR) for the association between age at T2D diagnosis and incident HHF (followed up until March 31, 2020). Results: Among 743,053 individuals with T2D and 2,199,539 matches, 126,241 incident HHF events occurred (median follow-up 8.9 years). T2D was associated with a greater adjusted hazard of HHF at younger ages (e.g., HR at age 30 years: 5.71, 95% CI: 5.46-5.96; Figure: Model 1) than at older ages (e.g., HR at age 60 years: 2.51, 2.46-2.55). Additional adjustment for recognized mediators (hypertension, coronary artery disease, chronic kidney disease) marginally attenuated this relation (Figure: Model 2). Conclusion: Younger age at T2D diagnosis is independently associated with a disproportionately elevated risk of HHF relative to age-matched individuals without T2D. This relation may be substantially mediated by novel mechanisms that are inadequately understood. Disclosure C. Ke: Advisory Panel; Sanofi, Speaker's Bureau; AstraZeneca, Abbott. B. R. Shah: None. J. Echouffo tcheugui: None. Funding National Heart, Lung, and Blood Institute (K23HL153774 to J.E.T.); University of Toronto (to B.R.S.)

COUNTERPOINT: the Seductive Trap of Relying on Exaggerated Effects in Short-Term Heart Failure Trials to Predict Benefits and Risks in Patients With Long-Term Disease

COUNTERPOINT: the Seductive Trap of Relying on Exaggerated Effects in Short-Term Heart Failure Trials to Predict Benefits and Risks in Patients With Long-Term Disease

P352 EXPLORATORY ANALYSES FROM APOLLO–B, A PHASE 3 STUDY OF PATISIRAN IN PATIENTS WITH ATTR AMYLOIDOSIS WITH CARDIOMYOPATHY

Abstract Introduction Transthyretin–mediated (ATTR) amyloidosis is a progressive and fatal disease. Patients with hereditary or wild–type ATTR amyloidosis frequently develop cardiomyopathy (CM). Patisiran, an IV RNAi therapeutic that inhibits synthesis of wt and variant TTR, is approved for the treatment of hATTR amyloidosis with polyneuropathy. Methods In APOLLO–B, patients were 18–85 yrs old with evidence of cardiac amyloidosis by echocardiography, ATTR amyloid deposition on tissue biopsy or fulfilling nonbiopsy diagnostic criteria for ATTR amyloidosis with CM, and had prior hospitalization for heart failure (HF) due to ATTR amyloidosis or clinical evidence of HF. Patients were randomized 1:1 to patisiran IV 0.3 mg/kg or placebo Q3W for 12 months. The primary endpoint was change from baseline in 6–MWT at Month 12 (M12) with patisiran vs placebo. Exploratory parameters at M12 included changes in cardiac biomarkers, echocardiography and Tc scintigraphy. Results APOLLO–B enrolled 360 patients (patisiran, n=181; placebo, n=179): median age, 76.0 yrs; male, 89%; wtATTR, 80%; on tafamidis at baseline, 25%. Patisiran showed a significant benefit compared with placebo in 6–MWT (median [95% CI] change from baseline: patisiran, –8.15 [–16.42, 1.50]; placebo, –21.35 [–34.05, –7.52]; HL estimate of median difference: 14.69 [0.69, 28.69]; p=0.0162). Patisiran demonstrated favorable trends in change from baseline of NT–proBNP (mean fold change ratio [95% CI]: 0.80 [0.73, 0.89]; p=1.825×10–5) and troponin I (mean fold change ratio [95% CI]: 0.87 [0.80, 0.95]; p=0.0011) at M12 vs placebo. Patisiran also demonstrated a trend towards benefit in change from baseline of most evaluated echocardiographic parameters at M12 vs placebo. Patisiran–treated patients evaluable for scintigraphy (n=37) experienced a reduction (37.8%) or no change (62.2%) in Perugini grade at M12 compared with baseline. Among placebo patients (n=28) at M12, none experienced a reduction from baseline in Perugini grade, and 1 (3.6%) increased in grade. Patisiran demonstrated an acceptable safety profile; AEs were mostly mild or moderate in severity, and there were no cardiac safety concerns. Conclusions Exploratory analyses after 12 months provide further evidence for the potential benefit of patisiran treatment on cardiac biomarkers and manifestations of cardiac amyloid involvement in patients with ATTR amyloidosis. The long–term impact of patisiran will be assessed in the ongoing APOLLO–B open–label extension.

Impact of coronary artery disease on outcome after transcatheter edge-to-edge mitral valve repair with the MitraClip system.

The clinical impact of coronary artery disease (CAD) on the prognosis of patients undergoing MitraClip implantation is still unclear. One thousand nine hundred fifty-three patients undergoing MitraClip implantation included in the multicenter GIOTTO Registry were stratified according to CAD. Endpoints were all-cause death, cardiac death, and re-hospitalization for heart failure at follow-up (median 15.8 months). Although younger, CAD patients were more symptomatic, had worse cardiovascular risk profile, higher burden of comorbidities, more frequently affected by functional MR, with higher left ventricle (LV) diameters and lower ejection fraction (EF). At follow-up, CAD patients showed higher rates of all-cause death (25.4% vs. 19.6%; P=0.002), cardiovascular death (14.0% vs. 10.1%; P=0.007) and re-hospitalization for heart failure (13.9% vs. 10.2%; P=0.011). Dividing the population according to mitral regurgitation (MR) etiology (functional vs. non-functional MR), no differences were observed between CAD and no-CAD patients. At multivariate logistic regression, NYHA III/IV class, prior heart failure hospitalization, severe chronic kidney disease, atrial fibrillation, LV end-diastolic diameter and LVEF<30% but not CAD resulted independent predictors of all-cause death. The same finding was confirmed even after propensity score adjustment. CAD did not show a relevant impact on mid-term prognosis per se, but seemed to identify a more complex and diseased cohort of patients with worse clinical and functional status.

Effect of Dapagliflozin on Total Heart Failure Events in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction

In the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial, dapagliflozin reduced the risk of time to first worsening heart failure (HF) event or cardiovascular death in patients with HF with mildly reduced or preserved ejection fraction (EF). To evaluate the effect of dapagliflozin on total (ie, first and recurrent) HF events and cardiovascular death in this population. In this prespecified analysis of the DELIVER trial, the proportional rates approach of Lin, Wei, Yang, and Ying (LWYY) and a joint frailty model were used to examine the effect of dapagliflozin on total HF events and cardiovascular death. Several subgroups were examined to test for heterogeneity in the effect of dapagliflozin, including left ventricular EF. Participants were enrolled from August 2018 to December 2020, and data were analyzed from August to October 2022. Dapagliflozin, 10 mg, once daily or matching placebo. The outcome was total episodes of worsening HF (hospitalization for HF or urgent HF visit requiring intravenous HF therapies) and cardiovascular death. Of 6263 included patients, 2747 (43.9%) were women, and the mean (SD) age was 71.7 (9.6) years. There were 1057 HF events and cardiovascular deaths in the placebo group compared with 815 in the dapagliflozin group. Patients with more HF events had features of more severe HF, such as higher N-terminal pro-B-type natriuretic peptide level, worse kidney function, more prior HF hospitalizations, and longer duration of HF, although EF was similar to those with no HF events. In the LWYY model, the rate ratio for total HF events and cardiovascular death for dapagliflozin compared with placebo was 0.77 (95% CI, 0.67-0.89; P < .001) compared with a hazard ratio of 0.82 (95% CI, 0.73-0.92; P < .001) in a traditional time to first event analysis. In the joint frailty model, the rate ratio was 0.72 (95% CI, 0.65-0.81; P < .001) for total HF events and 0.87 (95% CI, 0.72-1.05; P = .14) for cardiovascular death. The results were similar for total HF hospitalizations (without urgent HF visits) and cardiovascular death and in all subgroups, including those defined by EF. In the DELIVER trial, dapagliflozin reduced the rate of total HF events (first and subsequent HF hospitalizations and urgent HF visits) and cardiovascular death regardless of patient characteristics, including EF. ClinicalTrials.gov Identifier: NCT03619213.

What determines who gets cardiac resynchronization therapy in Europe? A comparison between ESC-HF-LT registry, SwedeHF registry, and ESC-CRT Survey II.

Cardiac resynchronization therapy (CRT) is effective in heart failure with reduced ejection fraction (HFrEF) and dyssynchrony but isunderutilized. In a cohort study, we identified clinical, organizational, and level of care factors linked to CRT implantation. We included HFrEF patients fulfilling study criteria in the ESC-HF-Long Term Registry (ESC-HF-LT, n=1031), the Swedish Heart Failure Registry (SwedeHF) (n=5008), and the ESC-CRT Survey II (n=11088). In ESC-HF-LT, 36% had a CRT indication of which 47% had CRT, 53% had indication but no CRT, and the remaining 54% had no indication and no CRT. In SwedeHF, these percentages were 30, 25, 75, and 70%. Median age of patients with CRT indication and CRT present vs. absent was 68 vs. 65 years with 24% vs. 22% women in ESC-HF-LT, 76 vs. 74 years with 26% vs. 26% women in SwedeHF, and 70 years with 24% women in CRT Survey II (all had CRT). For ESC-HF-LT, independent predictors of having CRT were guideline-directed medical therapy (GDMT), atrial fibrillation (AF), prior HF hospitalization, and NYHA class. For SwedeHF, they were GDMT, age, AF, previous myocardial infarction, lower NYHA class, enrolment at university hospital, and follow-up at HF centre/Hospital. In SwedeHF, above median income and higher education level were also independently associated with having CRT. In the ESC-CRT Survey II (n=11088), all patients received CRT but with differences in the clinical characteristics between countries. CRT was used in a minority of eligible patients and more used in ESC-HF-LT than in SwedeHF.