All-cause Hospitalization Research Articles

Exercise-based cardiac rehabilitation for patients with coronary artery operation: a systematic review and meta-analysis based on current randomized controlled trials

Background: Currently, exercise-based cardiac rehabilitation (CR) has been given increasing interest for its potentially beneficial effects on the health related quality of life (HRQoL) and outcomes of patients with coronary heart disease (CHD). The aim of this study was to evaluate the effect of exercise-based CR on patients after coronary artery bypass graſt (CABG) and percutaneous coronary interventions (PCI). Methods: We searched PubMed, Embase, Cochrane Library and Web of Science from inception to 1 December 2023 for relevant studies that evaluated the effect of exercise-based CR on patients after CABG and PCI. Our primary outcomes included the mortality, complications, hospital admissions and HRQoL between patients receiving exercise-based CR and usual care. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2 and Stata 12.0. Results: We finally indicated and included 25 randomized controlled trials (RCTs) with 4106 participants for the present analysis. Our pooled results indicated that, compared to usual care, exercise-based CR did not increasing the all-cause (RR 0.84; 95% CI 0.54 ‒ 1.31) and cardiovascular (RR 0.98; 95% CI 0.38 ‒ 2.54) mortality for patients after coronary artery operation. Similarly, exercise-based CR had equal effect on coronary artery complications for patients after coronary artery surgery, including CABG (RR 0.60; 95% CI 0.32 ‒ 1.15) and PCI (RR 0.92; 95% CI 0.55 ‒ 1.54). It was indicated that exercise-based CR significantly reduced the incidence of myocardial infarction (MI) by half with a RR of 0.50 (95% CI 0.28 ‒ 0.90). In addition, exercise-based CR also significantly reduced all-cause hospital admissions with a RR of 0.74 (95% CI 0.62 ‒ 0.88). Compared with usual care, exercise-based CR obviously improved HRQoL of patients after coronary artery operation evaluated with SF-36 summary scores (SMD 0.24; 95% CI 0.11 ‒ 0.38) and SF-36 8 domains (SMD 0.35; 95% CI 0.24 ‒ 0.46) respectively. Conclusions: Our analysis indicated that exercise-based CR had significant effect on the improvement of HRQoL of patients after coronary artery operation without increasing the mortality or incidence of re-intervention with operation.

Temporal Trends in Mortality and Hospitalization Risk in Patients With Heart Failure According to the Hospital Frailty Risk Score.

Heart failure (HF) and frailty often coexist. However, it is unknown how the interplay between HF and frailty at HF onset impacts prognosis of frail patients with HF and how this has evolved over time. We identified 131 235 patients with new-onset HF (median age 74 years, 39.7% women) from Danish nationwide registers in 1999 to 2017. Stratification according to the Hospital Frailty Risk Score resulted in (1) 102 635 (78%) nonfrail, (2) 26 054 (20%) moderately frail, and (3) 2609 (2%) severely frail patients. The proportion of moderately frail patients increased from 13.2% to 24.9%. Five-year absolute risks of all-cause mortality, HF hospitalization, and non-HF hospitalization were calculated using the Kaplan-Meier and Aalen-Johansen estimators. From 1999 to 2002 to 2003 to 2017, all-cause mortality risk (95% CI) declined from 56.4% (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 nonfrail, moderately frail, and severely frail patients, respectively. HF hospitalization risk remained almost constant over the study period. Non-HF hospitalization risk declined from 74.0% (73.5%-74.5%) to 65.8% (65.0%-66.5%) in nonfrail patients and remained stable overall in moderately frail and severely frail patients over the study period. We observed an increase in frail patients. Mortality decreased for all frailty groups but remained high for severely frail patients. These findings indicate the need for further evidence on the optimization of care for frail patients with HF, and future research should address the development of comprehensive management strategies, integrating frailty assessment into standard clinical care and focused care for older patients with HF.

Calcium channel blocker use and outcomes following transcatheter aortic valve intervention for aortic stenosis.

Calcium channel blockers (CCBs) are commonly used to treat coronary artery disease (CAD). The effects of the use of CCBs on the prognosis of patients with aortic stenosis (AS) after transcatheter aortic valve intervention (TAVI) has not been explored. This study elucidated the effects of the use of CCBs on clinical outcomes of patients who underwent TAVI for severe AS. This retrospective observational study included 993 consecutive patients who underwent TAVI for severe AS between January 2017 and July 2023. All patients were followed up for all-cause mortality and hospitalisation for heart failure. Composite endpoints between patients with and without CCBs at discharge were compared using propensity score matching (PSM). CCBs were administered to 590 (59.4%) patients following TAVI. Over a median follow-up period of 719 (335-1,120) days, the composite endpoint occurred in 269 patients. After PSM, there was no significant difference in the composite endpoint between the two groups (hazard ratio = 0.879; p = 0.409). Subgroup analysis revealed that the use of CCBs was associated with a better prognosis in the CAD subgroup (p for interaction = 0.002). This study does not suggest that the use of CCBs is associated with worse clinical outcomes in patients after TAVI for severe AS. Additionally, the use of CCBs may lead to a better prognosis in patients with CAD.

Operational Definitions of Polypharmacy and Their Association with All-Cause Hospitalization Risk: A Conceptual Framework Using Administrative Databases

Polypharmacy, defined as the concurrent use of multiple medications, increases the risk of various adverse outcomes. However, the variability in definitions across the literature contributes to substantial heterogeneity. Building on the published literature, this study aimed to identify a set of operational definitions of polypharmacy applicable to administrative databases and to assess their association with all-cause hospitalization. Data from the pharmacy refill and hospitalization databases of the Local Health Unit (LHU) of Bergamo, Lombardy, were analyzed. Patients aged ≥40 with at least one reimbursed drug prescription in 2017 were included. Prescription coverage was evaluated using total defined daily doses (DDDs), and all-cause hospitalizations from January to June 2018 were considered. Definitions explored included (i) the WHO’s criterion of ≥5 medications by ATC fourth-level code; (ii) the exclusion of prescriptions usually for short-term treatments; and (iii) drugs with cumulative annual DDD ≥ 60. Approaches were assessed annually, quarterly, and monthly, and logistic regression was used to estimate odds ratios (ORs) for hospitalization risk. Among 431,620 patients, the DDD ≥ 60 definition showed the least variability (20.47–21.16%) and identified an older more complex cohort. All definitions showed a dose-dependent association with hospitalization risk. Different definitions of polypharmacy result in varying prevalence, with DDD ≥ 60 being the most consistent. A patient-centric approach is crucial to assess the appropriateness of polypharmacy.

The usefulness of Charlson Comorbidity Index (CCI) scoring in predicting all-cause mortality in Outpatients with Clinical Diagnoses of COPD.

Since comorbid conditions are frequently present in chronic obstructive pulmonary disease (COPD) and affect outcome, a composite scoring system to quantify comorbidity might be helpful in assessing mortality risk. We tested the hypothesis that the Charlson Comorbidity Index (CCI) score at the time of an outpatient medical clinic encounter for COPD predicts all-cause mortality. Cox Proportional Hazards analyses were used in 200 randomly selected patients to relate CCI scores to all-cause mortality out to 5 years. Mean age was 62 ± 10 years, 56% were female, FEV1 was 62%, CCI was 3.08 ± 2.30, and 30% had a CCI ≥ 4, indicating 3 or more comorbid conditions. All-cause mortality was 8.5% and 20% at 3 and 5 years, respectively. In univariate testing, the CCI score and hospitalizations predicted mortality, but FEV1 did not. In multivariable testing, which included covariates of age, sex, socioeconomic status, race, FEV1 percent-predicted, and all-cause hospitalizations in the preceding year, CCI expressed as a continuous variable strongly predicted mortality: hazard ratio (HR) 1.38 for each unit increase in the score (p < 0.0001). While 1 or 2 comorbid conditions were not significantly related to mortality, 3 or more comorbid conditions (compared to none) strongly predicted mortality: HR 9.80, 95% CI 3.80 to 25.00. Comorbidity, assessed with the CCI, is strongly predictive of mortality in outpatients with a clinical diagnosis of COPD, and this relationship appears to be non-linear. This instrument may be useful in determining prognosis in this population.

Clinical outcomes among COVID-19 patients initiated on molnupiravir in Denmark - A national registry study.

Molnupiravir (MOV) is an orally bioavailable ribonucleoside with antiviral activity against all tested SARS-CoV-2 variants. We describe the demographic, clinical, and treatment characteristics of non-hospitalized Danish patients treated with MOV and their clinical outcomes following MOV initiation. Among all adults (>18years) who received MOV between 16 December 2021 and 30 April 2022 in an outpatient setting in Denmark, we summarized their demographic and clinical characteristics at baseline and post-MOV outcomes using descriptive statistics. Outcomes were emergent hospitalization and all-cause mortality during the 28 days after MOV initiation. We estimated the odds ratios (OR) of outcomes by time from positive test to treatment using logistic regression. We identified 3691 MOV-treated patients, of whom 45.8% were male and mean age was 70.1 years. Most patients (76.2%) initiated MOV within 0-2 days after a positive SARS-CoV-2 test and 16.8% within 3-5 days. Over a 28-day period, rates for all-cause, respiratory- or COVID-19-related, and COVID-19-related hospitalization were 4.8%, 2.6% and 1.5%, respectively. All-cause mortality was 1.6%. Initiation of MOV 3-5 days after a positive SARS-CoV-2 test compared to 1-2 days was associated with an increased risk of all-cause (OR 1.85, 95% CI 1.29-2.67) and respiratory or COVID-19-related (OR 1.78, 95% CI 1.07-2.94) hospitalization, and all-cause mortality (OR 2.90, 95% CI 1.64-5.15). MOV was primarily prescribed to vaccinated elderly persons with multiple comorbidities. The all-cause hospitalization and mortality rates in this population were low. Early initiation of MOV reduced the risk of hospitalization and death compared with late initiation.

The infected diabetic foot: Risk factors for re-infection after treatment for diabetic foot osteomyelitis.

Our objective was to evaluate risk factors for re-infection in patients after treatment for diabetic foot osteomyelitis (OM). We used pooled patient level data from two RTCs that evaluated patients with diabetic foot infections. We evaluated 171 patients with OM. OM was confirmed with bone culture or histopathology. Data from the 12-month follow-up were used to determine clinical outcomes. Re-infection occurred in 47 (27.5%) patients. Risk factors for re-infection were Toe Brachial Index <0.40 (25.7% vs. 9.8%, p = 0.02), skin perfusion pressure <40 mmHg (6.3% vs. 5.9%, p = 0.04), wound healing (55.3% vs. 75.0%, p = 0.01), time to heal (156.0, 69.5-365 vs. 91.5, 38.8-365, p = 0.001), and history of MI (14.9% vs. 3.2%, p = 0.005). During 12-month follow-up, patients with re-infections were 198.8 times more likely to require a foot related hospitalisation (81.8% vs. 0.0%, p = 0.001), 10.4 times more likely have an all-cause hospitalisation (70.2% vs. 18.5%, p = 0.001) and 9.4 times more likely to need an amputation (36.2% vs. 5.6%, p = 0.001). Patients with re-infection had a significantly longer median length of hospitalisation (20.0, 13.5-34.5 vs. 14.0, 10.0-22.0, p = 0.003) and median length of antibiotic duration (55.0, 35.0-87.0 vs. 46.0, 22.8-68.0, p = 0.03). Patients with re-infection are less likely to heal and have more foot-related hospitalizations and amputations.

Iron deficiency in acute coronary syndromes: prevalence and prognostic impact.

Iron deficiency (ID) is a well-known prognostic marker in heart failure (HF), independent of anemia. However, its impact in acute coronary syndromes (ACSs) is not well established. This is a retrospective analysis of patients admitted with ACS from January to December 2019. The population was evaluated according to basal characteristics and divided in two groups, with or without ID, compared according to several variables, namely demographic, index hospitalization, comorbidities, analytical and echocardiographic. We determined their predictive value on the occurrence of hemorrhage or need for red blood cell transfusion, all-cause hospitalizations, and all-cause death. We included 287 patients, with median age 66 (interquartile range [IQR] 21) years and 72% male. ID was present in 48% of patients. Most presented with ST-elevation myocardial infarction (STEMI) (57%), and 13% were admitted in Killip-Kimball class III or IV. Almost 40% had a left ventricle ejection fraction < 50% on admission. Patients with non-ST-elevation myocardial infarction presented more frequently with ID, compared with patients with STEMI. Of note, 33% of patients with ID had concomitant anemia. During a median follow-up of 28 (IQR 7) months, 10% had an urgent care admission for HF, 7% were hospitalized for HF, and 18% died. There was a significantly higher rate of emergency department admissions for HF in the group with ID. Age, anemia, and NT-proBNP levels predicted the occurrence of all-cause death, with ID having no impact on none of the evaluated events. ID was prevalent in patients with ACS, affecting almost half of the population. In the acute setting of an ACS, anemia seems to have a greater impact on mortality and the role of ID in promoting HF needs further investigation.

Clinical outcomes after transcatheter aortic valve implantation in nonagenarian patients: A retrospective population-based cohort study.

To compare the overall survival and the risk of all-cause and heart failure-specific hospitalization in nonagenarian patients hospitalized for symptomatic severe aortic stenosis (AS) who underwent transcatheter aortic valve implantation (TAVI) or conservative treatment. Population-based retrospective cohort study based on healthcare utilization databases of the Italian region of Lombardy. The cohort included all nonagenarians hospitalized for AS between 2017 and 2021, who underwent TAVI within 90 days from first diagnosis or conservative treatment. The association between TAVI and clinical outcomes was assessed through Cox or Fine&Grey regression models. High-dimensional propensity score matching was used to reduce the heterogeneity between groups. Overall, 16,848 nonagenarians hospitalized for AS were identified. Among these, 320 patients underwent TAVI, of which 193 were matched to as many control patients. The 2-year survival rates were 76.0 % and 37.7 %, respectively, in TAVI and control patients, corresponding to an HR of 0.24 (95 % CI 0.15-0.37). The 2-year cumulative incidence of rehospitalization for heart failure was 11.1 % and 26.5 %, respectively, corresponding to an HR of 0.64 (95 % CI 0.40-0.99). This study further supports the usefulness of TAVI in nonagenarians, as it showed to improve their survival rate, reduce their risk of rehospitalization, and likely increase their quality of life.

Phenomapping the Response of Patients With Ischemic Cardiomyopathy With Reduced Ejection Fraction to Surgical Revascularization.

Coronary artery bypass grafting (CABG) has demonstrated long-term mortality benefits in patients with HFREF and obstructive coronary artery disease (CAD), but whether phenotypic heterogeneity influences the benefits of CABG is unknown. We applied clustering analysis to STICHES (Surgical Treatment for Ischemic Heart Failure Extension Study) to identify phenogroups with different long-term risk profiles and investigate differences in CABG benefits between phenogroups. STICHES was a randomized controlled trial evaluating the effect of CABG in addition to medical therapy versus medical therapy alone. We split the STICHES participants into derivation (n = 753) and validation (n = 459) cohorts. We phenomapped the derivation cohort using penalized model-based clustering. We fit multivariable Cox models to investigate long-term differences in all-cause mortality, cardiovascular (CV) mortality, and a composite of all-cause mortality/CV hospitalization between phenogroups and whether phenogroup assignment modified the effects of CABG on these outcomes. Findings were internally validated on the validation cohort. Four phenogroups were identified in the derivation cohort. The highest-risk group was at a twofold greater risk of death (HR: 2.0, 95% CI: 1.4-2.9, p < 0.001) and CV death (HR: 2.0, 95% CI: 1.3-3.1, p = 0.002), and a 1.5-fold greater risk for death/CV hospitalization (HR: 1.5, 95% CI: 1.1-2.1, p = 0.016). Phenogroup assignment did not modify the effects of CABG on the outcomes (p > 0.05 for all). Similar results were obtained in the validation cohort. The beneficial effects of CABG on all-cause mortality, CV mortality, and a composite of all-cause mortality and CV hospitalization persist despite phenotypic heterogeneity in HFREF and CAD.

Atrial Fibrillation Recurrence Post-Ablation Across Heart Failure Categories: A Systematic Review and Meta-analysis.

Previous studies have provided evidence of reduced recurrence of atrial fibrillation (AF), all-cause mortality, and heart failure (HF) hospitalizations after catheter ablation (CA) in both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Aggregate data comparing the efficacy of AF ablation and clinical endpoints in HF with mildly reduced ejection fraction (HFmrEF) to HFrEF and HFpEF are lacking. We conducted a systematic review and meta-analysis aimed at determining any differences in AF recurrence rate, all-cause mortality, and HF hospitalizations among patients with HFrEF, HFmrEF, and HFpEF who underwent AF ablation. A systematic search of PubMed/MEDLINE, Embase, and Cochrane Library databases was performed until October 31, 2023. A total of seven studies comprising 3,795 patients were retained: HFrEF 1,281 (33.8%), HFmrEF 870 (22.9%), and HFpEF 1,644 (43.3%). After median follow-up of 24 months, there was no significant difference in rate of AF recurrence between the three HF categories: HFrEF 40% (30-49%), HFmrEF 35% (28-43%); and HFpEF 35% (25-45%). Only two studies which included outcomes in the three HF categories were identified. Pooled hazard ratio (HR) of all-cause mortality and HF hospitalization combined after ablation or other rhythm control compared to other conservative management were: HFrEF 0.77 (0.63 - 0.94); HFmrEF 0.81 (0.55 - 1.20); and HFpEF 0.74 (0.55 - 1.00). CA has similar efficacy in the long-term resolution of AF among patients with HFrEF, HFmrEF, and HFpEF. Further studies are needed to provide a robust analysis on the potential impact of CA on all-cause mortality.

Impact of Intensified Outpatient Follow-up on Rehospitalization after Transcatheter Aortic Valve Implantation: Results from the HOSPITAVI Trial.

Patients undergoing transcatheter aortic valve implantation (TAVI) are at increased risk of rehospitalization in the early period after discharge from TAVI. The HOSPITAVI study aimed to compare the impact of a standard vs. intensified outpatient follow-up on rehospitalization rates within 90 days after TAVI discharge. Patients were 1:1 randomized to either a standard or intensified outpatient follow-up after TAVI discharge. The primary endpoint was the 90-day hospital rehospitalization rate. In total, 300 patients were included: 150 patients were randomized to standard follow-up and 150 patients to intensified outpatient follow-up. The study population had a median age of 79 years, a median EuroSCORE II of 2.9%, and 72% were discharged the day after TAVI. Within 90 days after discharge, the mean number of all-cause hospital readmissions per patient was 0.44 vs. 0.35 (HR 0.8 [95%CI: 0.6-1.2], P=0.23) in the standard vs. intensified group, respectively. The mean number of cardiovascular (CV) readmissions per patient was 0.27 vs. 0.15 (HR 0.6 [95%CI: 0.4-1.0], P=0.04) in the standard vs. intensified group, respectively. This resulted in a mean number of CV readmission days per patient of 1.52 days vs. 0.49 days within the first 90 days in the standard vs. intensified group, respectively (P<0.05). Following TAVI discharge, there was no significant difference in all-cause rehospitalization rates using a standard vs. intensified outpatient follow-up approach. However, an intensified outpatient follow-up reduces the burden of early CV rehospitalization after TAVI discharge. (Rehospitalization after transcatheter aortic valve implantation [HOSPITAVI]; NCT05670041).

Antiviral efficacy of fluoxetine in early symptomatic COVID-19: an open-label, randomised, controlled, adaptive platform trial (PLATCOV).

The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine were repurposed for the treatment of early COVID-19 based on their antiviral activity invitro, and observational and clinical trial evidence suggesting they prevented progression to severe disease. However, these SSRIs have not been recommended in therapeutic guidelines and their antiviral activity invivo has not been characterised. PLATCOV is an open-label, multicentre, phase 2, randomised, controlled, adaptive pharmacometric platform trial running in Thailand, Brazil, Pakistan, and Laos. We recruited low-risk adult outpatients aged 18-50 with early symptomatic COVID-19 (symptoms <4 days) between 5 April 2022 and 8 May 2023. Patients were assigned using block randomisation to one of eleven treatment arms including oral fluoxetine (40mg/day for 7 days), or no study drug. Uniform randomisation ratios were applied across the active treatment groups while the no study drug group comprised ≥20% of patients at all times. The primary endpoint was the rate of oropharyngeal viral clearance assessed until day 7. Measurements were taken daily between days 0 and 7 and analysed in a modified intention-to-treat population (>2 days follow-up).The viral clearance rate was estimated under a Bayesian hierarchical linear model fitted to the log10 viral densities measured in standardised duplicate oropharyngeal swab eluates taken daily over one week (18 measurements per patient). Secondary endpoints were all-cause hospital admission at 28 days, and time to resolution of fever and symptoms. This ongoing trial is registered at ClinicalTrials.gov (NCT05041907). 271 patients were concurrently randomised to either fluoxetine (n=120) or no study drug (n=151). All patients had received at least one COVID-19 vaccine dose and 67% were female (182/271). In the primary analysis, viral clearance rates following fluoxetine were compatible with a small or no increase relative to the no study drug arm (15% increase; 95% credible interval (CrI):-2 to 34%). There were no deaths or hospitalisations in either arm. There were no significant differences in times to symptom resolution or fever clearance between the fluoxetine and the no study drug arms (although only a quarter of patients were febrile at baseline). Fluoxetine was well tolerated, there were no serious adverse events and only one grade 3 adverse event in the intervention arm. Overall, the evidence from this study is compatible with fluoxetine having a weak invivo antiviral activity against SARS-CoV-2, although the primary endpoint is also compatible with no effect. This level of antiviral efficacy is substantially less than with other currently available antiviral drugs. Wellcome Trust Grant ref: 223195/Z/21/Z through the COVID-19 Therapeutics Accelerator.

Prevalence and impact of comorbid mental disorders in hospitalized patients with obstructive sleep apnea (OSA): a nationwide study using administrative data.

This study aimed to compare the prevalence of mental comorbidities between hospitalization episodes with and without obstructive sleep apnea (OSA), andto analyze the association of those mental comorbiditieswith modifiable risk factors that may potentiate OSA. An observational retrospective analysis was conducted using an administrative database of discharges from all Portuguese mainland public hospitals. All-cause adult hospitalizations occurring between 2008-2015 were dichotomized according to the existence of an OSA code (ICD-9-CM 327.23). Mental disorders were clustered into categories 650-670 of Clinical Classifications Software. Within the OSA group, binary logistic regressions were performed to analyze associations between mental comorbidities and modifiable OSA risk factors. Of 6 072 538 admissions, 36 385 had a primary or secondary diagnosis of OSA, which was associated with greater odds of comorbid anxiety disorders (adjusted odds ratio[aOR] = 1.84), bipolar disorders (aOR = 2.68), depressive disorders (aOR = 2.38), alcohol abuse (aOR = 1.29) and suicidal behaviors (aOR = 1.52) compared to those without OSA (allp < 0.05). Each of these mental comorbidities was associated with significantly greater odds of at least two of the four studied risk factors that may potentiate OSA (namely obesity, smoking, alcohol abuse and opioid/sedative abuse). These findings emphasize the complex interplay between OSA and mental disorders, suggesting relevant bidirectional relationships, and highlight the importance of comprehensive assessment and management of mental health in individuals with OSA.

Real-world comparative effectiveness of sacubitril/valsartan versus RAS inhibition alone in patients with de novo heart failure.

Large-scale, real-world data on early initiation of sacubitril/valsartan in patients newly diagnosed (de novo) with HF with reduced ejection fraction (HFrEF) are limited. We examined the effectiveness of sacubitril/valsartan versus angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) on all-cause and cause-specific hospitalizations among patients with de novo HFrEF from the Optum® dataset in the United States. This retrospective cohort study included adult patients with de novo HFrEF (diagnosed ≤30days) with left ventricular ejection fraction (LVEF) ≤40% who were first prescribed with sacubitril/valsartan or ACEi/ARB from 1 January 2016 to 31 March 2020. The primary endpoint (all-cause hospitalization) and secondary endpoints were analysed in propensity score-matched cohorts. A cohort of 3290 patients with de novo HFrEF who were prescribed with sacubitril/valsartan and a propensity-matched cohort of 6580 patients who were prescribed with ACEi/ARB were analysed. Overall, the mean (SD) age of patients was 63 (14) years, 34% were women, and baseline characteristics were balanced across treatment groups. Hypertension (67%), diabetes (33%) and chronic kidney disease (28%) were highly prevalent comorbidities. Patients in the sacubitril/valsartan cohort when compared with the ACEi/ARB cohort had lower annual rates of all-cause hospitalizations [incidence rate ratio (IRR): 0.81, 95% confidence interval (CI): 0.75-0.89, P<0.001], cardiovascular (CV) hospitalizations (IRR: 0.80, 95% CI: 0.73-0.87, P<0.001) and HF hospitalizations (IRR: 0.86, 95% CI: 0.78-0.95, P=0.002). Among patients with de novo HFrEF, sacubitril/valsartan (compared with that of ACEi/ARB) was associated with fewer all-cause, CV and HF hospitalizations. These findings are consistent with clinical trial evidence suggesting potential benefits of early initiation of sacubitril/valsartan in patients with HFrEF, including those soon after diagnosis.

Prognostic value of echocardiography-based right ventricular-pulmonary artery coupling estimation in acute decompensated heart failure

Abstract Background Right ventricular-pulmonary artery coupling (RV-PA coupling) represents the relationship between RV contractility and RV afterload. RV-PA uncoupling occurs when RV contractility cannot increase to match RV afterload. This leads to RV dysfunction and right heart failure in the end. The value of RV-PA uncoupling in patients with chronic heart failure with reduced and preserved ejection fraction as a determinant of clinical status and strong predictor of cardiovascular death, rehospitalization for heart failure was demonstrated by literature worldwide. However, there are few studies estimated RV-PA uncoupling prognostic value in patients with acute decompensated heart failure (ADHF) upon admission. Purpose To assess echocardiographic parameter of RV-PA coupling and its prognostic value in patients with ADHF. Methods A single-centre observational study included 171 patients admitted to the city clinical hospital with ADHF (51.5% male, 70 (62;80) years old, arterial hypertension 93%, previous myocardial infarction 39.8%, HF with preserved ejection fraction (HFpEF) 36.8% (n=63), HF with reduced EF (HFrEF) 41.5% (n=71), HF with mid-range EF (HFmrEF) 21.6% (n=37), diabetes 36.8%, NYHA functional class III – 52.1%, class IV – 40.2%, NTproBNP 1683 (830;2944) pg/ml, serum creatinine 105 (86;126.4) µmol/l, eGFR 54.2 (44.1;67.8) ml/min/1.73 m2, potassium 4.5 ± 0.7 mmol/l, echocardiography parameters - left ventricle ejection fraction (LVEF) 44 (30;55)%, pulmonary artery systolic pressure (PASP) 51.2±17.3 mmHg, tricuspid annular plane systolic excursion (TAPSE) 15.4±4.7mm. RV-PA coupling estimated by the ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP) ratio was evaluated upon admission using two-dimensional echocardiography. TAPSE/PASP &amp;lt; 0.36 mm/mmHg was considered as RV-PA uncoupling. Survival analysis was perfomed using Kaplan-Meier curves. Differences were considered statistically significant when p &amp;lt;0.05. Results A statistically significant impact of RV-PA uncoupling on hospitalization, estimated by echocardiography, for heart failure (HF) and for all-cause hospitalization was revealed. Among patients with RV-PA uncoupling the risk of hospitalization for HF increased by 25% (RR 1.251; 95%CI: 1.020-1.539, p=0.042), and the risk of all-cause hospitalization - by 20-24% (RR 1.240; 95% CI: 1.001-1.537; p=0.049). Hospitalization rates for HF (OR 2.07; 95%CI: 1.02–4.02; p=0.042) and all-cause hospitalization (OR 1.96; 95%CI: 1.00–3.86; p=0.049) were 2 times higher. Conclusion: The identified prognostic value of echocardiography-based RV-PA uncoupling estimation in ADHF regardless of phenotype indicates the advisability of its assessment upon hospitalization. TAPSE/PASP can serve as an important simple tool for risk stratification of patients, optimizing their management and improving the long-term survival of patients.

Effective left ventricular ejection fraction by three-dimensional echocardiography is associated with survival and hospitalizations in ventricular secondary mitral regurgitation

Abstract Introduction Left ventricular (LV) systolic function is crucial for determining prognosis of patients with ventricular secondary mitral regurgitation (VsMR). However, both the LV ejection fraction (LVEF) and global longitudinal strain are influenced by the volume overload associated with MR. Effective LVEF (eLVEF) is a novel parameter that accounts for mitral regurgitant volumes and overcomes the load-dependency of LVEF. Pupose We sought to explore the association of eLVEF measured by three-dimensional (3D) echocardiography with mortality and heart failure (HF) hospitalizations in patients with VsMR. Methods We enrolled 212 VsMR patients (mean age 70±13 years, 26% female) from January 2015 to March 2022. 3D-eLVEF was calculated by dividing forward LV stroke volume (SV), measured by 2D-Doppler echocardiography by the LV end-diastolic volume measured by 3DE. The primary outcomes were all-cause mortality and HF hospitalization. Results During a mean follow-up of 22±11 months, 22% VsMR patients died and 28% had HF hospitalizations. In multivariable Cox regression, 3D-eLVEF was independently inversely associated with all-cause mortality (HR 0.93, 95%CI 0.89-0.97, p&amp;lt;0.001) and HF hospitalization (HR 0.95, 95%CI 0.92 – 0.99, p&amp;lt;0.001), outperforming 3D-LVEF and VsMR severity parameters. In ROC analysis, cut-off values associated with all-cause mortality were 3D-eLVEF≤24% (77% sensitivity, 61% specificity, AUC 0.74, 95%CI 0.67-0.79, p&amp;lt;0.0001), 3D-LVEF≤40% (87% sensitivity, 44% specificity, AUC 0.69, 95%CI 0.62-0.75, p&amp;lt;0.0001). Kaplan-Meier analysis demonstrated increasing event rate with 3D-eLVEF≤24% independent of LVEF higher or lower than 40% (log-rank, p&amp;lt;0.001). Patients with 3D-eLVEF≤24% and 3D-LVEF &amp;gt;40% had a worse prognosis than patients with 3D-LVEF≤40% and 3D-eLVEF&amp;gt;24% (log-rank, p&amp;lt;0.001). Those with 3D-eLVEF≤24% had the most HF hospitalizations, irrespective of 3D-LVEF (log-rank, p=0.002)(Figure 1). Conclusions In patients with VsMR, 3D-eLVEF was independently associated with all-cause mortality and HF hospitalization. 3D-eLVEF≤24% had a stronger association with both outcomes compared to 3D-LVEF≤40% and refined the risk stratification.

P-1993. Nirmatrelvir/Ritonavir in Immunocompromised Hosts: Use and Outcomes from a Cancer Center

Abstract Background Prolonged viral replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunocompromised (IC) hosts has raised questions about whether treatment duration with nirmatrelvir/ritonavir (nirmatrelvir/r) should be longer than the authorized 5-day course. Data describing nirmatrelvir/r treatment outcomes are limited in the IC population. The primary objective of this study was to assess the efficacy of a nirmatrelvir/r 5-day course as treatment for coronavirus disease 2019 (COVID-19) in IC patients. Methods A retrospective chart review was conducted at Fred Hutchinson Cancer Center (FHCC) of patients ≥ 18 years old with an active hematologic malignancy who received nirmatrelvir/r under Emergency Use Authorization between 12/22/21 - 5/25/23. Patients with an active oncology treatment plan within 3 months (before or after) their nirmatrelvir/r prescription date were included. Patients who received nirmatrelvir/r under Investigational New Drug authorization were excluded. The primary outcome was a composite of all-cause mortality or COVID-19 related hospitalization within 30 days of nirmatrelvir/r. A secondary outcome, persistent COVID-19 infection, was defined as a positive SARS-CoV-2 polymerase chain reaction test 30-90 days after initial positive test. Results Among 928 patients who received nirmatrelvir/r at FHCC, 399 patients were included. Median age was 63 years, 55% of patients were male, and lymphoma was the most common malignancy, 48% (Table 1). Thirty-day all-cause mortality or COVID-19 related hospitalization occurred in 39/399 (9.8%) of patients. Thirteen patients (3.3%) had persistent COVID-19 infection; 8 had persistent symptoms and 5 required additional treatment. Early discontinuation of nirmatrelvir/r due to adverse effects, most commonly gastrointestinal, occurred in 11 (2.8%) patients (Table 2). Conclusion Incidence of the primary outcome was higher in our population compared to rates in nirmatrelvir/r phase 3 trial data and driven by hospitalization rather than all-cause mortality. Persistent infection requiring further treatment occurred in only 1.3% of patients. Additional studies are needed to define optimal treatment duration, including potential indications for use &amp;gt; 5 days in IC hosts. Disclosures Frank Tverdek, PharmD, Merck: Advisor/Consultant Catherine Liu, MD, Pfizer: Grant/Research Support

P-1768. Evaluation of Pharmacist-Driven Automatic 5-day Stop Dates for Ceftriaxone in Respiratory Tract Infections

Abstract Background Despite 2019 ATS/IDSA CAP guideline support for a 5-day treatment duration, compliance with these recommendations remains suboptimal. Patients that receive extended courses of antibiotics are at increased risk for adverse outcomes, longer hospitalization stays, and development of antimicrobial resistance. The objective of this study was to compare hospital length of stay (LOS) and length of therapy (LOT) before and after a pharmacist-driven automatic stop date protocol for ceftriaxone for CAP and COPD exacerbations. Methods A retrospective cohort study conducted at Texas Health Harris Methodist Hospital Fort Worth evaluated patients before June 2023, and after November 2023. Patients were excluded if treatment indications were for non-respiratory indications, received ≤2 ceftriaxone doses, admitted into the ICU, LOS ≥10 days, or if placed on hospice within 72 hours of admission. Pharmacists then adjusted ceftriaxone orders to 5 total days for CAP and COPD exacerbations. The primary outcome was hospital LOS and LOT. Secondary outcomes included 30-day all-cause in-hospital mortality and 30-day hospital readmission due to infections. Results 295 patients were included in the final analysis with 145 patients in the pre- and 150 patients in the post-group. After implementation of the protocol, a statistically significant reduction in hospital LOS was observed in the post-group (4 days vs 5 days, p &amp;lt; 0.0001). There was also a statistically significant reduction in median LOT for CAP and COPD (5 days vs 7 days, p &amp;lt; 0.0001). No increase in 30-day all-cause mortality (0% vs 4%, p =0.012) or 30-day hospital re-admission rates due to infections (3% vs 8%, p =0.033) were observed in the post- compared to the pre-group. Conclusion Based on the results of this study, implementation of a pharmacist-driven automatic 5-day stop date protocol for ceftriaxone is an effective antimicrobial stewardship initiative that can help increase compliance to guideline recommendations for CAP and COPD while also decreasing hospital LOS. Additionally, this initiative was not associated with increased rates of mortality or hospital re-admissions compared to longer durations and influenced discharge antibiotic prescription habits. Disclosures All Authors: No reported disclosures

P-1928. Virologic and Clinical Outcomes Among Participants Hospitalized in a Phase 3 Trial Comparing Molnupiravir with Placebo for Treating Mild-to-Moderate COVID-19

Abstract Background The correlation between virologic and clinical outcomes in COVID-19 remains unclear. The objective of this analysis was to assess SARS-CoV-2 viral load (VL) and laboratory biomarkers in participants who did and did not progress to hospitalization in the phase 3 component of the MOVe-OUT trial.Table 1.Baseline demographics and characteristics of participants who did and did not progress to hospitalization*One participant in the placebo group with an unknown hospitalization status was not included in this analysis. Methods In MOVe-OUT, unvaccinated adults with mild-to-moderate COVID-19 at risk for disease progression were randomized 1:1 to molnupiravir (MOV) 800-mg or placebo (PBO) every 12 hours for 5 days. The primary efficacy endpoint was all-cause hospitalization or death through day 29. In this analysis, the following were evaluated in the modified intent-to-treat (MITT; randomized, received ≥1 dose of study drug, and not hospitalized prior to 1st dose) population (1408 participants) at baseline and at postbaseline time points: VL (quantitative PCR), high-sensitivity C-reactive protein (CRP), and absolute lymphocyte count (ALC).Figure 1.Mean change in SARS-CoV-2 viral load in hospitalized and non-hospitalized participants (A) and SARS-CoV-2 viral load over time in hospitalized participants (B)Hospitalization ± 48 hours excluding baseline.One participant in the placebo group with an unknown hospitalization status was not included in this analysis. Results 115 (8.2%) participants progressed to hospitalization (HP). HP were more likely vs those who remained non-hospitalized (NHP) to be male; ≥65 years; with active cancer, diabetes mellitus, moderate COVID-19, and negative nucleocapsid and neutralizing antibody status at baseline (Table 1). Mean time from symptom onset to hospitalization, and randomization to hospitalization, was 8.9 and 5.3 days. In HP, mean VL at baseline was 7.51 vs 6.83 log10 copies/mL among NHP. Among HP, VL declined in 37/38 (97.4%) MOV and 50/63 (79.4%) PBO-treated participants, respectively, between baseline and the day of hospitalization. Mean decline in VL from baseline to day 5 was 1.90 (SD 1.53) in HP vs 2.12 (SD 1.62) log10 copies/mL in NHP, with greater declines observed in MOV vs PBO-treated participants at all time points (Figure 1). Mean CRP was higher at baseline in HP vs NHP (49.93 vs 16.77 mg/L), and postbaseline values increased in HP and decreased in NHP. Alternatively, mean ALC was lower at baseline in HP vs NHP (1.07 vs 1.54 109/L), and postbaseline values continued to decrease at day 3 and 5 in HP while values increased in NHP (Table 2).Table 2.Mean change in C-reactive protein and absolute lymphocyte count in hospitalized and non-hospitalized participantsHospitalization ± 48 hours excluding baseline. Conclusion HP had a higher VL at baseline, with a smaller decline over time than NHP. A higher VL at baseline in conjunction with an increasing CRP and decreasing ALC may help identify patients with mild-to-moderate COVID-19 at higher risk for hospitalization. Disclosures Matthew G. Johnson, MD, Merck &amp; Co., Inc.: I have an interest in a patent application for the company.|Merck &amp; Co., Inc.: Employee of Merck &amp; Co., Inc.|Merck &amp; Co., Inc.: Stocks/Bonds (Public Company) David W. Hilbert, PhD, Merck &amp; Co., Inc.: Employee of Merck &amp; Co., Inc.|Merck &amp; Co., Inc.: Stocks/Bonds (Public Company) Erin Jensen, MS, Merck &amp; Co., Inc.: Employee of Merck &amp; Co., Inc.|Merck &amp; Co., Inc.: Stocks/Bonds (Public Company) Dorothy McCoy, PharmD, Merck &amp; Co., Inc.: Employee of Merck &amp; Co., Inc.|Merck &amp; Co., Inc.: Stocks/Bonds (Public Company) Brian Maas, PharmD, Merck &amp; Co., Inc.: Employee of Merck &amp; Co., Inc.|Merck &amp; Co., Inc.: Stocks/Bonds (Public Company) Ying Zhang, PhD, Merck &amp; Co., Inc.: Employee of Merck &amp; Co., Inc.|Merck &amp; Co., Inc.: Stocks/Bonds (Public Company) Michelle L. Brown, BS, Merck &amp; Co., Inc.: Employee of Merck &amp; Co., Inc.|Merck &amp; Co., Inc.: Stocks/Bonds (Public Company) Dana L. Byrne, MD, Merck &amp; Co., Inc.: Employee of Merck &amp; Co., Inc.|Merck &amp; Co., Inc.: Stocks/Bonds (Public Company) Carisa S. De Anda, PharmD, Merck &amp; Co., Inc.: MOV patent|Merck &amp; Co., Inc.: Employee of Merck &amp; Co., Inc.|Merck &amp; Co., Inc.: Stocks/Bonds (Public Company)