All-cause Hospitalization Research Articles

Impact of sex-specific thresholds for low flow in assessment of prognosis in concordantly and discordantly graded aortic valve stenosis.

Sex-specific low flow was recently defined as stroke volume index (SVi) ≤40 ml/m² in men and ≤32 ml/m² in women. We tested the prognostic association of these cut-offs in patients with aortic stenosis (AS) with concordantly and discordantly graded AS (CGASEL and DGASEL) based on pressure recovery adjusted aortic valve area (energy loss, EL). Data from 1351 patients with asymptomatic AS, peak jet velocity <4m/s and preserved left ventricular ejection fraction enrolled in the Simvastatin and Ezetimibe in AS study was used. DGASEL was defined as EL <1.0 cm² with mean aortic gradient <40 mmHg, and CGASEL as EL ≥1.0 cm² with mean aortic gradient <40mmHg. Patients were further grouped into normal and low flow. Outcome was combined all-cause death and hospitalization for heart failure. CGASEL with normal/low flow was present in 915/253 patients, and DGASEL with normal/low flow in 57/126 patients. During median 4.3 years follow-up, event-free survival was lower in patients with DGASEL irrespective of flow compared to CGASEL with normal flow (p<0.05). In Cox regression analysis, DGASEL with normal or low flow were both associated with increased risk of all-cause death and hospitalization for heart failure after adjustment for age, sex, heart rate, randomized study treatment, hypertension, aortic valve replacement and aortic valve calcification (p<0.05). No survival difference was found between patients with normal vs. low flow within groups of DGASEL or CGASEL. Identification of low flow by the proposed sex-specific thresholds of SVi needs more prognostic validation before application in clinical practice.

Lung Ultrasound in the Acute Phase of ST-Segment-Elevation Acute Myocardial Infarction: 1-Year Prognosis and Improvement in Risk Prediction.

Lung ultrasound (LUS) has emerged as a useful tool in the acute phase of patients admitted for ST-segment-elevation myocardial infarction. However, its long-term significance remains uncertain, and risk scores do not include LUS findings as a predictor. This study aims to assess the 1-year prognostic value of LUS and its ability to enhance existing risk scores. This is a multicenter prospective cohort study involving 373 patients with ST-segment-elevation myocardial infarction. LUS was performed during the first 24 hours after angiography. LUS results were assessed both as a categorical (wet/dry lung) and continuous variable (LUS score). The primary end point comprised the following major adverse cardiovascular events: all-cause mortality or hospitalization for heart failure, acute coronary syndrome, or stroke within 1 year. We also evaluated whether LUS could enhance the predictive value of the GRACE (Global Registry of Acute Coronary Events) score. Major adverse cardiovascular events occurred in 51 (13.7%) patients over a median follow-up of 368 days. After multivariate analysis, the LUS score was an independent predictor (hazard ratio [HR], 1.06 [95% CI, 1.01-1.10]; P=0.009] for each additional B-line), whereas the categorical classification was an independent predictor in patients with ST-segment-elevation myocardial infarction Killip I (HR, 3.12 [95% CI, 1.34-7.31]; P=0.009). Incorporating LUS into GRACE resulted in a net reclassification index of 31.6% and a significant increase in the area under the curve; GRACE alone scored 0.705 compared with GRACE+LUS 0.791 (P=0.002). Detecting B-lines on LUS at the acute phase predicts major adverse cardiovascular events at 1 year in patients with ST-segment-elevation myocardial infarction and enhances the predictive value of the GRACE score. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04526535.

Diuretic dosing and outcomes with torsemide and furosemide following hospitalization for heart failure: the TRANSFORM-HF trial

Abstract Background The TRANSFORM-HF trial found no significant difference in all-cause mortality and all-cause hospitalization following hospitalization for heart failure (HF) with a diuretic strategy of torsemide versus furosemide. However, the impact of diuretic dosing on the trial results and whether the relationship between dosing and outcomes differs between torsemide and furosemide is unclear. Purpose To assess and compare the associations between diuretic dosing and outcomes with torsemide and furosemide. Methods TRANSFORM-HF was an open-label, pragmatic trial that randomized 2859 patients hospitalized for HF in the United States to a diuretic strategy of torsemide versus furosemide after discharge. These post-hoc analyses categorized patients according to investigator-selected discharge dose tertile of torsemide and furosemide, i.e. tertile 1) ≤40 mg, 2) &amp;gt;40-80 mg and 3) &amp;gt;80 mg of furosemide equivalents using a 2:1 conversion with torsemide. Study endpoints were all-cause mortality, all-cause hospitalization, composite all-cause mortality or hospitalization, and change from baseline to 12 months in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). Results Dosing data were available for 2379 (83%) of patients with median age 65 years (IQR: 56, 75), 883 (37.1%) were women, and 812 (34.2%) were Black. When categorized by discharge dose, a total of 1136 (47.8%) patients were included in dose tertile 1, 696 (29.2%) in tertile 2 and 547 (23.0%) in tertile 3. For all-cause mortality, furosemide showed adjusted hazard ratios (aHR) of 1.21 (95% CI: 0.91, 1.59) for tertile 2 and 1.40 (95% CI: 1.04, 1.88) for tertile 3 compared with tertile 1. For torsemide aHR for all-cause mortality were 1.74 (95% CI: 1.32, 2.30) for tertile 2 and 1.58 (95% CI: 1.14, 2.19) for tertile 3 compared with tertile 1 (Table 1). The risk of adverse events increased similarly with dose for both diuretics and no statistically significant interaction between loop diuretic and dose was observed (Pinteraction=0.17). Likewise, for the endpoints of all-cause hospitalization and the composite of all-cause mortality and hospitalization, higher doses of furosemide and torsemide aligned with higher risk of both endpoints, and interaction p-values that did not demonstrate statistical significance by loop diuretic (all-cause hospitalization: Pinteraction= 0.28, all-cause mortality and hospitalization: Pinteraction=0.38) (Table 1). Changes in KCCQ-CSS were similar across the range of dose tertiles from baseline to month 12 for both furosemide and torsemide (Table 2). Conclusions Following hospitalization for HF, no clinical differences were observed across the dosing spectrum in all-cause mortality, all-cause hospitalization, or KCCQ-CSS at 12-mornths between torsemide and furosemide. Irrespective of diuretic agent used, increasing dose of loop diuretics correlates with worse clinical outcomes.

Effects of Sacubitril/Valsartan on all-cause hospitalizations in heart failure: participant-level pooled analysis of PARADIGM-HF and PARAGON-HF

Abstract Background Sacubitril/valsartan is indicated to reduce the risk of cardiovascular (CV) death and heart failure (HF) hospitalizations in patients with chronic HF. However, many of these patients are older and have multiple comorbidities that increase the risk of hospitalizations other than HF, yet the effects of sacubitril/valsartan on hospitalizations of any cause have not been well described. Methods PARADIGM-HF and PARAGON-HF were phase-3, global multicenter randomized clinical trials that evaluated sacubitril/valsartan versus enalapril (in PARADIGM-HF) or valsartan (in PARAGON-HF) across the spectrum of left ventricular ejection fraction (LVEF; ≤40% in PARADIGM-HF and ≥45% in PARAGON-HF). We pooled individual participant-level data from these 2 trials to examine the effects of sacubitril/valsartan on time-to-first investigator-reported all-cause and cause-specific hospitalization using Cox proportional hazards models, stratified by geographic region and trial. We additionally examined heterogeneity in treatment response by LVEF. Results Over 2.8 years median follow-up, among 13,194 participants in the pooled PARADIGM-HF/PARAGON-HF, sacubitril/valsartan significantly reduced the risk of all-cause hospitalizations compared with renin-angiotensin system inhibitor (HR 0.92; 95% CI 0.88-0.97; P=0.002); Figure 1 Panel A. The absolute risk reduction (ARR) was 2.1 per 100 patient-years corresponding to a number-needed-to-treat (NNT) of 48 patient-years of treatment exposure to prevent 1 all-cause hospitalization. Reductions in overall hospitalizations among patients with identifiable causes (N=5,783) seemed to be primarily driven by lower rates of cardiac and pulmonary hospitalizations associated with sacubitril/valsartan. Patients treated with sacubitril/valsartan did not have a higher rate of composite non-cardiac hospitalizations (Figure 1 Panel B). Similarly, sacubitril/valsartan reduced the risk of the composite of all-cause hospitalization or all-cause mortality (HR 0.92; 95% CI 0.87-0.96; P&amp;lt;0.001), with an ARR of 2.5 per 100 patients-years and an NNT of 40 patient-years. For all-cause hospitalization, we observed significant heterogeneity by LVEF as a continuous measure (Pinteraction=0.027); treatment effects were most apparent in those with an LVEF below 60% (HR 0.91 95% CI 0.86-0.96; Figure 2). Conclusions In a pooled analysis of &amp;gt;13,000 patients with chronic HF, sacubitril/valsartan reduced hospitalization for any reason with benefits most apparent among those with an LVEF below normal.

Anxiety or depression in heart failure across the ejection fraction spectrum

Abstract Background Anxiety or depression are commonly described in patients with heart failure (HF) but few data exist on characteristics and clinical outcomes associated with anxiety or depression across the different HF phenotypes. Purpose To assess the prevalence of patient characteristics and clinical outcomes associated with anxiety or depression in patients with HF with preserved, mildly reduced and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF). Methods Patients enrolled in the Swedish Heart Failure Registry between 2000-2021 were included. Self-reported anxiety or depression was collected using EuroQoL 5-dimensional questionnaire (EQ-5D) at baseline and follow-up visits. Anxiety or depression was categorized as "not anxious or depressed", "moderately anxious or depressed" or "severe anxious or depressed". The independent associations between baseline characteristics and presence of anxiety or depression were assessed by a multivariable multinominal regression analysis. Cox proportional hazards regressions were performed to model the time to first event according to levels of anxiety or depression. Outcomes included all-cause death and all-cause hospitalizations. Results A total of 45,247 patients were included among whom 58% reported none, 38% moderate and 5% severe anxious or depressed with similar distribution across the HF phenotypes (Figure). Several characteristics were associated with anxiety or depression with the strongest ones for severe versus none being higher NYHA class (OR 3.10 (2.77-3.47)), liver disease (OR 1.99 (1.56-2.55)), in-patient setting (OR 1.62 (1.43-1.84)), smoking (OR 1.75 (1.52-2.00)) while others were inversely related including male sex (OR 0.51 (0.46-0.56)), higher age (OR 0.60 (0.53-0.67)), referral to HF nurse clinic (OR 0.82 (0.72-0.94)) and higher income level (OR 0.68 (0.62-0.76)). The risk of all-cause death and all-cause hospitalizations increased with increasing levels of anxiety or depression across all HF phenotypes during 12 months of follow up. Severe anxiety or depression had a stronger association with all-cause death in hospitalized patients and all-cause hospitalizations in out-patients. Conclusion In this large contemporary cohort of patients with HF in a real-world setting, anxiety or depression was frequently and similarly distributed across all HF phenotypes. Higher NYHA class, liver disease and in-patient setting were strongly associated with the anxiety or depression while male sex, higher age, and higher income were inversely related with anxiety or depression. Anxiety or depression was significantly associated with worse outcomes at 12 months follow up.Proportion anxiety or depression

Torsemide versus furosemide in patients with heart failure: a systematic review and meta-analysis

Abstract Introduction Loop diuretics are essential agents in the management of fluid overload conditions, heart failure and renal dysfunction. Despite their widespread use, there is ongoing debate regarding the relative efficacy, safety, and clinical outcomes associated with furosemide and torsemide. By systematically analyzing existing literature, this study seeks to provide a comprehensive evaluation of the comparative effectiveness and safety profiles of these two medications , Helping to inform clinical decision-making and contribute to the optimization of diuretic therapy in patients with heart and kidney diseases. Methods We searched PubMed, Scopus, WOS, and Cochrane until February 2024 for relevant studies comparing the torsemide and furosemide in Heart failure patients. Outcomes of interest were all-cause mortality, cardiovascular mortality, all-cause hospitalization, hospitalization for HF, and improvement of ≥ 1 in NYHA functional class. Results 16 studies were included in this meta-analysis with a total of 12545 patients, There were no significant results between the two drugs in all-cause mortality, cardiovascular mortality or all-cause hospitalization, torsemide showed a reduction in hospitalization from heart failure (RR 0.85, 95% CI [0.71 to 1.02]), torsemide showed a significant improvement of ≥ 1 in NYHA functional class (OR 1.60, 95% CI [1.18, 2.17]). Conclusion There was no difference between torsemide and furosemide when it comes to all-cause and cardiovascular mortality, but torsemide showed better results in reducing hospitalization rates and and improving quality of life.Hospitalization from heart failureImprovement ≥ 1 in NYHA class

Long-term effects of patisiran on survival and cardiac parameters in patients with transthyretin-mediated cardiac amyloidosis: post hoc analysis of APOLLO-B and cardiac subpopulation of APOLLO OLE

Abstract Introduction Transthyretin-mediated (ATTR) amyloidosis is a progressive, fatal disease in which the most serious manifestations are polyneuropathy and cardiomyopathy. Patients with hereditary ATTR (ATTRv; v for variant) amyloidosis commonly develop a mixed phenotype, and patients with wild-type ATTR amyloidosis predominantly have cardiomyopathy, although polyneuropathy may coexist. Patisiran, an RNAi therapeutic that rapidly knocks down TTR, has shown long-term benefit on measures of polyneuropathy in the APOLLO open-label extension (OLE) study in patients with ATTRv amyloidosis. Purpose To evaluate the long-term benefit of patisiran on survival, hospitalisations and cardiac parameters in a pooled cohort of patients with ATTR amyloidosis and evidence of cardiac involvement, across the patisiran clinical programme (Phase [Ph] 2 launched in 2012). Methods Post hoc analysis of pooled data from cardiac subpopulations of patients with ATTRv amyloidosis and polyneuropathy from 5-year Global OLE (Ph 2 OLE and Ph 3 APOLLO; patients with baseline left ventricular [LV] wall thickness ≥13 mm; absence of history of aortic valve disease or hypertension), and Ph 3 APOLLO-B (patients with wild-type or ATTRv cardiac amyloidosis). Patients received patisiran or placebo every 3 weeks for 18 months in APOLLO and 12 months in APOLLO-B; all patients received patisiran thereafter. Analyses included Kaplan-Meier estimates and Cox regression of survival and all-cause hospitalisations, and summary statistics of cardiac biomarkers and echocardiographic parameters by initial treatment arm. Results Pooled analysis included 496 patients (initial arm placebo, n=214; initial arm patisiran, n=282). Compared with placebo, patients initially receiving patisiran had better long-term survival and fewer hospitalisations (hazard ratio [95% confidence interval] over 84 months for all-cause mortality and all-cause hospitalisations: 0.59 [0.37–0.93] [Figure 1] and 0.77 [0.60–0.99], respectively). At baseline, NT-proBNP and troponin I levels, peak longitudinal strain and LV wall thickness were comparable between patisiran vs placebo-treated patients. Placebo-treated patients showed worsening of all these parameters whilst on placebo; the rates of worsening decreased once the patients initiated patisiran. In contrast, patients who initially received patisiran demonstrated relative stability over 84 months in the Global OLE and significant benefit compared with those initially treated with placebo. Conclusion Long-term benefit of patisiran in patients with cardiomyopathy was observed on survival, hospitalisations, cardiac biomarkers and echocardiographic parameters. Outcomes were significantly more favourable for those initially randomised to patisiran than placebo, highlighting the impact of initiating treatment early in the course of disease.

Effect of renin-angiotensin system inhibitors in elderly patients with heart failure and reduced ejection fraction

Abstract Background More than half of the patients admitted for acute decompensated heart failure (ADHF) in Japan are over 80 years of age. Both Japanese and European heart failure guidelines recommend the use of renin-angiotensin system inhibitors (RASIs) in patients with heart failure with reduced ejection fraction (HFrEF). However, there is a paucity of data on the effect of RASIs in elderly patients with HFrEF, because elderly patients have been excluded from large clinical trials. Purpose The purpose of the current study was to clarify the effect of RASIs in elderly patients with HFrEF. Methods This was a post-hoc analysis of a prospective, observational, multicentre cohort study that enrolled consecutive patients admitted with ADHF to 19 secondary and tertiary hospitals in Japan between October 2014 and March 2016. Patients who were ≥ 80 years old, with left ventricular ejection fraction (LVEF) &amp;lt; 40% and discharged alive were included in the present study. RASIs were defined as either ACE inhibitors or angiotensin II receptor blockers. The primary endpoint was a composite of all-cause death and heart failure (HF) hospitalisation. Results Among 518 patients enrolled, 288 patients received RASIs at discharge and 230 patients did not. The median follow-up period was 335 days (interquartile range; 124 – 499 days). Patients receiving RASIs were younger (85.7 ± 4.4 vs. 86.5 ± 4.4 years of age, p=0.03), had a higher body mass index (BMI; 21.4 ± 3.3 vs. 20.6 ± 3.7 kg/m², p=0.01) and better renal function (eGFR; 45.4 ± 21.5 vs. 38.2 ± 19.2 ml/min/1.73m², p&amp;lt;0.001). Patients receiving RASIs had a higher LVEF (30.9 ± 6.3 vs. 28.5 ± 7.1%, p&amp;lt;0.001). The use of beta-blockers at discharge was more prevalent in patients receiving RASIs (77.8% vs. 60.4%, p&amp;lt;0.001), but the use of mineralocorticoid receptor antagonists was not (50.0% vs. 42.2%, p=0.08). The cumulative incidence of all-cause death or HF hospitalisation one year after discharge was significantly lower in patients receiving RASIs (40.1% vs. 59.5%, p&amp;lt;0.001). Even after adjusting for confounders, the risk of a composite of all-cause death and HF hospitalisation was significantly lower in patients receiving RASIs (adjusted hazard ratio 0.59, 95% confidence interval 0.45-0.77, p&amp;lt;0.001). There was no interaction between the effect of RASIs and subgroup factors such as age, BMI, dementia, malignancy, frailty, and renal function. Conclusion Use of RASIs at discharge was associated with lower incidence of all-cause death or HF hospitalisation in elderly patients with HFrEF.

Long-term all-cause and cardiovascular-related mortality in patients with ATTR-CM treated with continuous tafamidis vs placebo to tafamidis by NAC stage at baseline

Abstract Background The National Amyloidosis Centre (NAC) staging system is used to stratify patients with transthyretin amyloid cardiomyopathy (ATTR-CM) into prognostic categories.[1] Purpose This post hoc analysis evaluated all-cause and cardiovascular (CV)-related mortality in patients receiving tafamidis 80 mg or placebo by NAC stage at baseline in the phase 3 Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and its long-term extension (LTE) study.[2,3] Methods Patients in ATTR-ACT were randomised to tafamidis meglumine 80 mg, 20 mg, or placebo for 30 months, stratified by transthyretin (TTR) genotype (wild-type or variant) and NYHA class (I or II/III). Patients with an NT-proBNP &amp;lt;600 ng/l or eGFR &amp;lt;25 ml/min/1.73m² were excluded. After completing ATTR-ACT, patients could receive tafamidis 61 mg up to 60 months in the open-label LTE study. Heart transplant and cardiac mechanical assist device implantation were treated as death in the mortality assessments. Secondary analyses were change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical and overall summary (CS, OS) scores and frequency of all-cause and CV-related hospitalisations. Results Of 350 patients, 42%, 38% and 20% had NAC stage I, II and III at baseline, respectively. Patients at stage III tended to be older, more likely female, and with a variant TTR genotype vs those at a lower stage (Table). At the end of follow-up, all-cause mortality was consistently lower in patients continuously treated with tafamidis vs those who initially received placebo across NAC stages (I: 36% vs 61%; : 55% vs 74%; III: 69% vs 88%). The hazard ratio (HR [95% CI]) for all-cause mortality with continuous tafamidis treatment vs placebo to tafamidis was 0.43 (0.26-0.70; P&amp;lt;0.001), 0.51 (0.33-0.80; P=0.003) and 0.75 (0.44-1.29; P=0.298), for patients at stage I, II and III, respectively. Similar trends were observed in CV-related mortality at the end of follow-up, where HR (95% CI) for continuous tafamidis-treated patients at stage I, II and III was 0.39 (0.22-0.70; P=0.001), 0.51 (0.31-0.85; P=0.009) and 0.75 (0.42-1.33; P=0.320). The separation of survival curves was seen in the first few months of tafamidis treatment in patients at NAC stage I (Figure A). Such early separation was not seen in those at stage II or III. Starting from Month 18, statistically smaller declines in KCCQ-OS and CS scores were frequently observed in the continuous tafamidis vs placebo to tafamidis groups at stages I and II. Across NAC stages, all-cause and CV-related hospitalisations were lower in the continuous tafamidis vs placebo to tafamidis group (Figure B). Conclusions Continuous tafamidis treatment reduced mortality and hospitalisations (both all-cause and CV-related) across all NAC stages. These reductions were larger and occurred earlier in patients with NAC stage I, emphasising the importance of early disease-modifying treatment in patients with ATTR-CM.[3] NCT01994889, NCT02791230.

Supplemental Oxygen Use, Outcomes, and Spending in Patients With COPD in the Medicare Competitive Bidding Program.

The Medicare Competitive Bidding Program (CBP), a policy that reduced durable medical equipment prices, was implemented starting in 2011. Legislation introduced in 2024 aims to remove supplemental oxygen from the CBP because of concerns that recent decreases in oxygen prescribing are due to lower prices set by the CBP, which may have decreased supply and, in turn, limited oxygen access for patients with chronic lung diseases. However, low-value prescribing of oxygen is also prevalent in practice, and decreased oxygen prescription rates may not have necessarily caused harm. Little is known about the association of the CBP with patient use, outcomes, or spending. To examine the association between the 2011 and 2013 implementation of the CBP and supplemental oxygen use, clinical outcomes, and supplemental oxygen spending among patients with chronic obstructive pulmonary disease (COPD). This cohort study used a difference-in-differences (DID) method to evaluate the association between implementation of the CBP and the outcomes of interest. Patients aged 65 to 100 years with COPD living in CBP areas were compared with those living in areas where the CBP was not yet or never implemented. The study included 100% fee-for-service Medicare data of beneficiaries enrolled between July 1, 2009, and December 31, 2015. The data analysis was performed between June 6, 2023, and August 16, 2024. The 2011 and 2013 implementation cycles of the Medicare CBP. The primary outcomes were new prescriptions of oxygen during a 6-month period among beneficiaries with COPD and discontinuation of oxygen during a 6-month period among beneficiaries with COPD previously prescribed oxygen. Secondary outcomes included switches between oxygen types (gas, liquid, or concentrator), all-cause mortality, all-cause unplanned hospitalizations, COPD hospitalizations, and mean monthly allowed charges (total spending) over a 6-month period. The analysis was performed using the Callaway-Sant'Anna method, a dynamic DID model for policies with staggered implementation. Among 5 753 308 Medicare beneficiaries with COPD (mean [SD] age, 79.2 [8.4] years; 55.1% female), 25.9% received supplemental oxygen for at least one 6-month period during the study. The CBP was not associated with differential changes in new oxygen prescribing (DID estimate, -0.19 percentage points; 95% CI, -2.45 to 2.08 percentage points) or oxygen discontinuations (DID estimate, -0.77 percentage points; 95% CI, -8.15 to 6.60 percentage points). Similarly, differential changes were not observed in the secondary outcomes of oxygen switches (DID estimate, -0.04 percentage points; 95% CI, -0.44 to 0.37 percentage points), all-cause mortality (DID estimate, 0.16 percentage points; 95% CI, -7.52 to 7.84 percentage points), all-cause unplanned hospitalizations (DID estimate, -0.20 percentage points; 95% CI, -10.94 to 10.53 percentage points), or COPD hospitalizations (DID estimate, -0.04 percentage points; 95% CI, -2.57 to 2.48 percentage points). Differential changes were observed for mean monthly allowed charges (DID estimate, -$326.22; 95% CI, -$434.76 to -$217.68). In this study, among beneficiaries with COPD, the Medicare CBP was associated with differentially lower spending but not differential changes in oxygen use or clinical outcomes. This study did not find evidence supporting ongoing policy efforts to remove supplemental oxygen from the CBP.

SGLT2 inhibitors in patients with amyloidosis and heart failure: a worldwide retrospective cohort study

Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the combined risk of death and hospitalization in patients with heart failure with reduced or preserved left ventricular ejection fraction. However, evidence of their impact on patients with heart failure due to amyloidosis is lacking. Purpose To evaluate the effects of SGLT2 inhibitors on mortality and hospitalization in patients with amyloidosis and heart failure. Methods In this retrospective cohort study, we used real-world data from 108 healthcare organizations worldwide from the global health research collaborative network TriNetX. We identified 24,619 patients with amyloidosis and heart failure without exposure to SGLT2 inhibitors (control group) and 2,988 patients with amyloidosis and heart failure under treatment with SGLT2 inhibitors (SGLTi group). We performed propensity score matching for demographic and clinical characteristics and Kaplan–Meier plots, log-rank tests, and Cox proportional hazard models were calculated. The outcomes were 12-month all-cause death and 12-month hospitalization. Results After propensity score matching, 2,237 patients were analyzed in each group. During the 12-month follow-up, 198 (8.8%) patients died in the SGLT2i group, and 431 (19.2%) patients died in the control group (hazard ratio 0.51, 95% CI 0.43-0.61). In the SGLT2i group, 974 (44.5%) patients were hospitalized, and in the control group, 1508 (53.5%) patients were hospitalized (hazard ratio 0,79, 95% CI 0.72-0.86). The Kaplan-Meier curves are shown in Figure 1. Conclusions In conclusion, in this retrospective cohort study with a large number of patients with amyloidosis and heart failure, SGLT2 inhibitors were associated with a lower 12-month all-cause mortality and hospitalization. Further evidence from randomized controlled studies are needed to confirm the efficacy of SGLT2 inhibitors in patients with cardiac amyloidosis.Figure 1.Kaplan-Meier curves

Influence of process-focused patient care on clinical outcomes among hospitalized heart failure patients in the cardiology ward

Abstract Background The implementation of a process-oriented organizational structure in patient care allows for a comprehensive and optimized approach. In the context of heart failure (HF), it remains uncertain whether the establishment of a specialized hospitalisation team can contribute to improved major clinical outcomes. Purpose To analyse the rates of all-cause hospitalisation, cardiovascular hospitalization, HF hospitalization and overall mortality at 180 days among patients admitted to the Cardiology ward for HF, both prior to and after the implementation of a specialized HF hospitalisation team. Methods The study included all patients discharged from the Cardiology department with HF as the primary diagnosis and subsequent outpatient follow-up by the Community HF Unit in both 2019 and 2022. Clinical outcomes were compared between two distinct periods: the pre-implementation year of 2019 and the subsequent year of 2022, characterized by process-oriented HF care. Statistical analyses were performed using Kaplan-Meier and adjusted Cox proportional-hazards models. Results A total of 140 patients were enrolled in the study, comprising 55 individuals receiving care from a conventional ward team in 2019 and 85 under the specialized HF team in 2022. The mean age of the cohort was 69.4 years (+/-11.8), with a mean LVEF of 40.6%. The pre-implementation group showed a higher percentage of male patients (73% vs. 47%; p=0.003) and LVEF was lower in the HF team period (38.9% vs. 43.4%; p=0.045), with no statistically significant differences in other baseline variables. As shown in figure 1, over 180 days of follow-up, 15 patients (27.6%) were admitted to hospital in the conventional ward team period and 13 (15.3%) in the HF team period (hazard ratio [HR] 0.44; 95% confidence interval [CI] 0.19 to 0.99; P=0.047). Of these hospitalisations, 13 patients (23.6%) in pre-implementation period and 10 (11.8%) in post-implementation period were attributed to cardiovascular events (HR 0.40; 95% CI 0.16 to 0.99; P=0.049). Additionally, there was a reduction in the rate of heart failure admissions in the post-implementation period compared to the pre-implementation time (HR 0.30; 95% CI 0.09 to 0.94; P=0.039). Furthermore, a significant decline in all-cause of death was observed in patients treated by HF-team in 2022 compared to patients receiving care from the conventional ward team (log-rank test, p=0.015). Conclusions The implementation of a process-oriented organizational model within the Cardiology unit consisting in the provision of patient care by a team specialized in HF management, is associated with a statistically significant reduction in major clinical outcomes such as all-cause hospitalization, cardiovascular hospitalization and HF readmission, alongside a reduction in overall mortality rates at 180 days.

Visit-to-visit HbA1c variability and risk of potentially avoidable hospitalisations in adults with type 2 diabetes receiving outpatient care at a tertiary hospital.

This study aims to investigate the relationship between long-term visit-to-visit within-person HbA1c variability and hospitalisation outcomes in adults with type 2 diabetes (T2D). We conducted a cohort study at a tertiary hospital in Singapore involving people aged 21 to 101 years with T2D who had ≥3 HbA1c tests over 2 years. HbA1c variability was assessed using coefficient of variation (CV), variability independent of the mean (VIM) and HbA1c variability score (HVS). A 1-year follow-up was performed after the last HbA1c measurement to identify all-cause and potentially avoidable hospitalisations (PAH), categorised as overall, acute, chronic and diabetes composites. The study included 14 923 patients (mean age: 62.9 ± 12.9 years; 55% male). The median HbA1c variability was 8.6% CV (IQR: 5.1-14.3). Higher quartiles of HbA1c variability were associated with greater risks of PAH and all-cause hospitalisations, independent of glycaemic control. Compared to Q1, for example, the risk ratios and 95% confidence intervals for diabetes-related PAH based on HbA1c CV were as follows: Q2, 1.32 (0.93-1.88); Q3, 1.65 (1.18-2.31) and Q4, 2.16 (1.54-3.03). For all-cause hospitalisations, they were as follows: Q2, 0.97 (0.90-1.05); Q3, 1.08 (1.00-1.17) and Q4, 1.16 (1.07-1.26). When stratified by glycaemic control, elevated risk of PAH persisted even in those with optimal glycaemic control. Consistent findings were observed using HbA1c VIM and HVS measures. In individuals receiving care at specialist outpatient clinics of a tertiary hospital, HbA1c variability is associated with a higher risk of PAH. Comprehensive diabetes management strategies addressing both glycaemic control and variability may offer benefits.

Relative effectiveness of high-dose versus standard-dose quadrivalent influenza vaccine against hospitalizations and mortality according to frailty score: a post-hoc analysis of the DANFLU-1 trial

Abstract Background Frailty is a major risk factor for adverse cardiovascular events. Influenza vaccination has been shown to protect against cardiovascular fatal and nonfatal events. However, limited data exist on the added benefit of high-dose versus standard-dose influenza vaccination according to frailty status. Purpose We sought to assess the relative effectiveness of high-dose (QIV-HD) versus standard-dose (QIV-SD) quadrivalent influenza vaccination according to frailty status in elderly individuals. Methods This is a post-hoc analysis of the randomized controlled feasibility trial of QIV-HD versus QIV-SD conducted during the 2021–2022 influenza season in adults aged 65–79 years. We assessed the following prespecified outcomes: hospitalizations for pneumonia or influenza, cardio-respiratory hospitalizations, cardiovascular hospitalizations, all-cause hospitalizations and all-cause mortality. Level of frailty was defined according to the Hospital Frailty Risk Score based on ICD-10 codes for relevant comorbidities any time prior to vaccination. We divided the participants into two categories according to Frailty Score (FS): low frailty (0-4 points) and intermediate or high frailty (≥5 points). We analyzed outcomes as time to first event using Cox proportional hazards regression. Results Among 12,473 randomly assigned participants to QIV-HD versus QIV-SD (mean age 71.7 years, 47.1% female), 10,711 (85.9%) were categorized as having low frailty and 1,762 (14.1%) had intermediate or high frailty. In total, 38 individuals were hospitalized for pneumonia or influenza during follow-up, 219 were hospitalized for cardiorespiratory illness, 1055 were hospitalized due to any cause and 62 died during follow-up. FS significantly modified the effect of QIV-HD versus QIV-SD for all-cause mortality (P for interaction 0.02). In participants with low frailty, QIV-HD was associated with a lower risk of all-cause mortality (Figure 1: HR 0.26, 95% CI 0.13 to 0.55), whereas there was no evidence of effect among those with intermediate or high frailty (HR 1.68, 95% CI 0.66 to 4.26). QIV-HD versus QIV-SD was associated with a lower incidence of hospitalizations for pneumonia and influenza, this effect was consistent regardless of frailty status (P for interaction 0.88). QIV-HD was not associated with a significantly lower incidence of hospitalizations due to cardiovascular, cardiorespiratory or respiratory disease or any cause regardless of frailty status. Conclusions In this post-hoc analysis of a large-scale pragmatic trial, QIV-HD was similarly associated with a lower incidence of hospitalizations for pneumonia and influenza among older adults irrespective of frailty status. The potential benefit of QIV-HD versus QIV-SD may therefore be applicable regardless of frailty status. However, our results suggest that QIV-HD is associated with a lower risk of all-cause mortality among adults with low frailty only.Figure 1.

Characterizing disease burden and health care resource utilization in patients with hypertrophic cardiomyopathy: a nationwide real-world study in Finland

Abstract Background Hypertrophic cardiomyopathy (HCM) is an often hereditary myocardial disease with an estimated prevalence of 1:500 in the general population. Purpose This study aimed to investigate healthcare resource utilization (HCRU) and associated costs in patients diagnosed with HCM (and the associated subtypes: obstructive or non-obstructive) in a nationwide cohort in Finland. Methods This retrospective, registry-based cohort study included all Finnish patients diagnosed with HCM between 2000 and 2021, who were 12+ years old at the time of diagnosis, as identified from the national care registers for healthcare. HCRU data were collected between 2014 and 2021 from the Finnish national care registers for health care and the social insurance institution. Data pertaining to New York Heart Association (NYHA) classification were collected from three Finnish university hospitals. Results The study cohort comprised 5,834 patients with an HCM diagnosis; obstructive HCM accounted for 34% of cases. Mean per patient-year costs were €6638, 95% confidence interval (CI) €6472-€7415, and €6112, 95% CI €5957-€6560 for those with obstructive and non-obstructive HCM respectively. All-cause hospitalizations at specialized care were the most prominent cost associated with patients with obstructive and non-obstructive HCM equating to 46.3% and 46.1% of the total cost respectively (Fig 1.). Comorbidity burden, as measured by Charlson comorbidity index (CCI) score, was greater in patients with the obstructive than non-obstructive phenotype of the disease (CCI ≥4: 2.2 and 1.8, p&amp;lt;0.01, respectively). The highest utilization of invasive procedures was found for patients with NYHA class III-IV. Conclusion This population-based study, utilizing real-world data, provides novel insights into HCRU and related costs among Finnish patients with HCM (and associated subtypes). HCRU appears to be primarily driven by hospitalizations at specialized care. Furthermore, the data indicate that patients with obstructive HCM are likely to have a more severe disease, with higher comorbidity burden and requiring more invasive procedures than patients with the non-obstructive form of the disease. However, there were no statistically significant differences in health care costs between those with obstructive and non-obstructive HCM.

Relative effectiveness of high-dose vs. standard-dose quadrivalent influenza vaccine according to time of day of vaccination: a post-hoc analysis of the DANFLU-1 randomised clinical trial

Abstract Background Circadian variations have been shown to affect antibody response following vaccination. We sought to evaluate whether time of day of vaccination (ToV) modified the relative effectiveness of high-dose (QIV-HD) vs. standard-dose (QIV-SD) quadrivalent influenza vaccination, and further whether ToV was independently associated with hospitalisations and mortality. Methods This is a post-hoc analysis of the DANFLU-1 trial which was a randomized trial of QIV-HD vs. QIV-SD in adults aged 65-79 years conducted during the 2021-2022 influenza season. Vaccination took place between 7:05 AM and 8:08 PM. For this study, we stratified participants into early and late vaccination groups according to ToV before or after 11 AM, respectively. Prespecified outcomes included hospitalisations for pneumonia or influenza, respiratory disease, cardiovascular disease, and cardio-respiratory disease as well as all-cause hospitalisations and mortality. Hospitalisations were analysed as recurrent events using negative binomial regression, while mortality was analysed using Cox proportional hazard models, both of which were also used to test for interaction. For multivariable analysis, models were adjusted for baseline risk factors including sex, age, and multiple lung diseases. ToV was furthermore assessed as a continuous variable with 2-hour increments. Results In the final study population, the early group consisted of 5,371 (43%) participants (mean age 71.6±3.9 years, male sex 53.6%, QIV-SD 50.1%), while the late group consisted of 7,106 (57%) (mean age 71.8±4.0 years, male sex 52.4%, QIV-HD 49.9%). During follow-up, we observed 43 hospitalisations for pneumonia or influenza, 76 respiratory hospitalisations, and 62 mortalities. In recurrent event analysis, QIV-HD was associated with lower incidence of hospitalisation for pneumonia or influenza compared with QIV-SD irrespective of whether administered early (IRR 0.17 (95% CI 0.03-0.86), p=0.032) or late (IRR 0.37 (95% CI 0.16-0.88), p=0.024) (p-value for interaction = 0.69) (Figure 1). Effect estimates were consistent for all outcomes excluding cardiovascular hospitalisations regardless of early or late vaccination, and no effect modification was found (Figure 1). Interestingly, late vaccination was associated with higher incidence rate of respiratory hospitalisation (IRR 3.00 (95% CI 1.13-7.98), p=0.024, Figure 2), irrespective of vaccine type. The same association was found for ToV as a continuous variable (IRR 1.28 per 2-hour increment (95% CI 1.02-1.60), p=0.035). All above associations remained significant in multivariable analysis. Conclusion QIV-HD was associated with lower incidence of hospitalisation for pneumonia or influenza regardless of time of day for vaccination. In addition, later vaccination was associated with higher incidence of respiratory hospitalisation independent of vaccine type and known risk factors. Due to low power, however, this finding should be regarded as exploratory.Figure 1:Forest plotFigure 2:Incidence rates

Impact of a clinician-to-clinician electronic consultation program in heart failure patients with previous hospitalization. Implications for heart failure multidisciplinary management

Abstract Background A clinician-to-clinician electronic consultation (e-consultation) programme may not only improve the accessibility to care but may also impact patient outcomes, particularly in heart failure (HF) patients with a previous episode of hospitalization (HFH), group of patients associated with a worse outcome. Purpose To evaluate the impact of an outpatient care management programme that includes a clinician-to-clinician e-consultation on delay time in care, hospital admissions, and mortality in a high-risk group of patients with heart failure (HF) and previous episodes of HF hospitalization (HFH). Materials and methods We selected 6444 HF patients who visited the cardiology service at least once between 2010 and 2021. Of these, 4146 were attended in e-consultation, and 2230 had previous HFH (Fig 1a). Using an interrupted time series regression model, we analysed the impact of incorporating e-consultation into the healthcare model in the group of patients with HFH and evaluated the elapsed time to cardiology care, HF, cardiovascular (CV), and all-cause hospital admissions and mortality, calculating the incidence relative risk (iRR). We performed a multivariate logistic regression for each of these outcomes in both groups. Results Patients with HFH had a higher prevalence of men (P &amp;lt; 0.001) but had a similar age (P = 0.267) compared to patients without HFH. Patients with HFH had a higher prevalence of diabetes (P &amp;lt; 0.001), ischaemic heart disease (P = 0.036), and peripheral arterial disease (P = 0.008) (Fig 1b). In the group of patients with HFH, the introduction of e-consult substantially decreased waiting times to cardiology care (8.6 [8.7] vs. 55.4 [79.9] days, P &amp;lt; 0.001) (Fig 2a). In that group of patients, after e-consult implantation, hospital admissions for HF were reduced (iRR [95%CI]: 0.837 [0.840–0.833]), 0.900 [0.862–0.949] for CV and 0.699 [0.678–0.726] for all-cause hospitalizations (Fig 2b). There was also lower mortality (iRR [95%CI]: 0.715 [0.657–0.798] due to HF, 0.737 [0.764–0.706] for CV and 0.687 [0.652–0.718] for all-cause) (Fig 2c). The improved outcomes after e-consultation implementation were significantly higher in the group of patients with previous HFH. The multivariate analyses showed a higher risk of hospitalizations in men, patients with HFH, and those who required more emergency department assistance (Fig 2d). Conclusions In patients with HFH, an outpatient care programme that includes an e-consultation significantly reduced waiting times to cardiology care and was safe, with a lower rate of hospital admissions and mortality in the first year. Our results may have implications for optimize the heart failure care organization.Figure 1Figure 2

Automated digital counselling with social network support for chronic heart failure fails to improve health status but promotes health-related quality of life: ODYSSEE-vCHAT pilot trial

Abstract Background Automated digital counselling programs have the potential to provide a scalable, complementary behavioural intervention to improve clinical outcomes for chronic heart failure (CHF). Purpose The primary hypothesis for this pilot trial was that automated digital counseling with social network support (ODYSSEE-vCHAT) vs. Usual Care would decrease the incidence of all-cause re-hospitalization or ED visits. Secondary outcomes included: minimal clinically important difference for improvement on the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS), and improvement on ENRICHD Social Support Index (ESSI), Patient Health Questionnaire for Depression (PHQ-9) Godin-Shephard Leisure Time Physical Activity Scale (GSLTPAQ), and Self-Efficacy in Managing Chronic Disease (SEMCD6). Methods This 2-arm, parallel group, single-blind pilot trial randomized patients to ODYSSEE-vCHAT vs. Usual Care. Patients were ≥18 years of age with CHF (reduced ejection fraction [HFrEF] &amp;lt; 40%, mid-range [HFmrEF] 40-49%, or preserved [HFpEF] ≥ 50%). Exclusion was based on inability to participate due to co-morbidities. All-cause hospitalization or ED visit were assessed digitally by hospital administrative data. Questionnaires were administered at baseline and end-of-study (approximately 8 months). The digital counselling protocol aimed to improve CHF self-care, HRQL, and adherence to medications, exercise, diet, and smoke-free living (Figure 1). The primary outcome was assessed using multivariable binary logistic regression. Secondary outcomes were assessed using multivariable linear regression analyses with ethno-racial group as a covariate. Results 61 patients were randomized: ODYSSEE-vCHAT, n = 30 (49%), vs. Usual Care, n = 31 (51%). There were 2 deaths, 3 withdrawals, and 12 patients failed to complete secondary outcome assessments. Sample characteristics included mean age = 59 years (95% Confidence Interval, CI, 30, 76), gender identity as women, n = 23 (38%), ethno-racial group other than White, n = 17, (28%) and CHF with HFrEF, n = 47 (77%), HFmrEF, n = 8 (13%), and HFpEF, n = 4 (7%). Duration of enrollment to trial endpoint: mean = 247 days, (95% CI, 75, 382). Figure 2 indicates that ODYSSEE-vCHAT was not associated with lower incidence of all-cause hospitalization/ED visit: composite index events for Usual Care, n = 8 (28%), ODYSSEE-vCHAT, n = 7 (23%). However, ODYSSEE-vCHAT was associated with greater prevalence of KCCQ-OS change (≥ 5 points), and greater improvement in self-efficacy (SEMCD6) for managing CHF. There was a statistical trend to decreased prevalence of depression. Social support was inversely associated with ODYSSEE-vCHAT. No benefit was observed for physical activity (Figure 2). Conclusions Automated digital counselling with social network support promotes improvement in HRQL indices, but not health status. Findings for this pilot trial support a follow-up phase 2 randomized controlled trial.Digital Counselling ProtocolODYSSEE-vCHAT Outcomes

Electronic consultation from primary care to a cardiology department improves outcomes in patients with cancer

Abstract Background The number of cancer patients with known cardiovascular (CV) disease is increasing due to improved cancer prognosis. Purpose The objective of this study is to assess the long-term results of cancer patients referred to a cardiology department by primary care using electronic consultation (e-consultation). Methods We analysed the patients with previous diagnosis of cancer referred to a cardiology department (CD) from 2010 to 2021 (n=6.889), selected from a total of 68.518 patients (61.629 without cancer), and compared two assistance models: in-person practice (from 2010 to 2012) and e-consultation (from 2013 to 2021). In the first period, all the patients referred by primary care physicians (PCPs) were seen in an in-person consultation and in the e-consultation model the cardiologist reviewed the electronic records (e-consultation) and decided to solve without any visit or, if it was necessary, with an in-person consultation. The outcomes between both periods were analysed using an interrupted time series regression model: 1) delay time to cardiology assistance; 2) all-cause and cardiovascular hospital admissions, and 3) all-cause and cardiovascular mortality during the first year after the initial consultation or e-consultation to the CD. Results Among cancer patients referred to cardiology consultation, the introduction of e-consultation decreased waiting times to cardiology care by 51,8% (95% CI: 51,7%-51,9%) (Fig 1). Over 60% of referrals were resolved in less than 8 days, with this proportion significantly higher after the e-consultation program was introduced (p&amp;lt;0,001). Furthermore, we observed a reduction in the one-year rate of outcomes, with an incidence rate ratio (iRR) [IC 95%] of 0,75 [0,73-0,77] for CV-related hospitalizations (Fig 2b), 0,43 [0,42-0,44] for all-cause hospitalization (Fig 2a), and 0,87 [0,86-0,88] for all-cause mortality. In the multivariate analysis, the delay in receiving cardiology care was significantly associated with an independent increase in 1-year mortality (OR [95% CI] 1,39 [1,06-1,83]) and hospital admission (OR [95% CI] 1,25 [1,02-1,52]). Furthermore, the implementation of the e-consult model was associated with a reduction in hospital admission rates (OR [95% CI] 0,19 [0,14-0,25]). Conclusions In comparison to the in-person consultation period, an outpatient care program that incorporates e-consultation for cancer patients significantly reduced waiting times for cardiology care and shown to be safe, associated with lower rates of hospital admissions.Figure 1Figure 2

Temporal trends in mortality and hospitalisation risk in patients with heart failure according to frailty status

Abstract Background Heart failure (HF) and frailty often coexist, and patients with both conditions have a higher risk of mortality and hospitalisation compared with those who are not frail. Over the past two decades, advances in medication targeting HF have been introduced, prolonging the life of patients with HF, but also resulting in increased comorbidity accumulation and susceptibility to frailty. It remains unknown how the interplay between HF and frailty at HF onset impacts patient prognosis and how this has changed over time. Purpose We investigated the temporal trends in the risk of all-cause mortality and HF hospitalisation in patients with HF from 1999 to 2017 according to their frailty status. Methods From Danish nationwide registers, we included patients with new-onset HF. Patients were categorised into four groups according to the year of HF onset: 1999-2002, 2003-2007, 2008-2012, and 2013-2017. The Hospital Frailty Risk Score was used to classify patients into frailty severity categories: 1) non-frail, 2) moderately frail, and 3) severely frail. The primary outcome was the 5-year cumulative incidence of all-cause mortality, assessed using the Kaplan-Meier estimator. The secondary outcome was the 5-year risk of HF hospitalisation, assessed using the Aalen-Johansen estimator, accounting for the competing risk of death. Moreover, a sensitivity analysis was conducted using a multivariable Cox proportional hazard model, investigating the interaction between year group and frailty status for all-cause mortality, comparing frail patients with non-frail patients. Results Among 131,235 patients with HF (median age 74 years; 39.7% female), 102,635 (78%) were categorised as non-frail, 26,054 (20%) as moderately frail, and 2609 (2%) as severely frail. The proportion of moderately frail patients increased the most, from 13% in 1999 to 25% in 2017. From 1999-2002 to 2003-2017, the 5-year cumulative incidence of all-cause mortality declined from 56.4% (95% CI, 55.8-57.0%) to 33.3% (32.6-34.1%), 79.8% (78.5-81.0%) to 58.6% (57.2-60.1%), and 90.8% (85.6-96.0%) to 79.8% (76.4-83.2%) in the non-frail, moderately frail, and severely frail patient group, respectively (Fig 1). The largest relative improvement was observed in the non-frail patient group. The 5-year cumulative incidence of HF hospitalisation remained fairly constant across the frailty groups (Fig 2). Conclusions From 1999 to 2017, we observed an increase in moderately and severely frail patients. Overall, the mortality risk decreased across all frailty groups. These findings underscore the importance of implementing guidelines directed at frail patients with HF.5-year risk of all-cause mortality5-year risk of HF hospitalisation