Heart Failure With Reduced Ejection Fraction Polypill Implementation Strategy in India: A Convergent Parallel Mixed Methods Study.

Introduction: A polypill-based implementation strategy has been proposed to increase rates of guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction. This has the potential to improve mortality and morbidity in India and undertreated populations globally. Methods: We conducted a convergent parallel mixed methods study integrating quantitative data from stakeholder surveys using modified implementation science outcome measures and qualitative data from key informant in-depth interviews. Our objective was to explore physician, nurse, pharmacist, and patient perspectives on a HFrEF polypill implementation strategy in India from January 2021 to April 2021. Quantitative and qualitative data were integrated to develop an Implementation Research Logic Model. Results: Among 69 respondents to the stakeholder survey, there was moderate acceptability (mean [SD] 3.8 [1.0]), appropriateness (3.6 [1.0]), and feasibility (3.7 [1.0]) of HFrEF polypill implementation strategy. Participants in the key-informant in-depth interviews (n = 20) highlighted numerous relative advantages of the HFrEF polypill innovation including potential to simplify medication regimens and improve patient adherence. Key relative disadvantages elucidated, include concerns about side effects and interruption of multiple GDMT medications due to polypill discontinuation for side effects or hospitalizations. Based on this data, the proposed implementation strategies in the Implementation Research Logic Model include 1) HFrEF polypills, 2) HFrEF polypill initiation, titration, and maintenance protocols, and 3) HFrEF polypill laboratory monitoring protocols for safety which we postulate will lead to desired clinical and implementation outcomes through multiple mechanisms including increased medication adherence to a single pill. Conclusion: This study demonstrates that a HFrEF polypill-based implementation strategy is considered acceptable, feasible, and appropriate among healthcare providers in India. We identified contextually relevant determinants, strategies, mechanism, and outcomes outlined in an Implementation Research Logic Model to inform future research to improve heart failure care in South Asia.

Guideline-directed medical therapy prescribing patterns and in-hospital outcomes among heart failure patients during COVID-19.

Study objective: The association of prior to admission guideline-directed medical therapy (GDMT) use in patients hospitalized with Heart Failure with Reduced Ejection Fraction (HFrEF, ejection fraction ≤40 %) and Coronavirus Disease 2019 (COVID-19) with in-hospital outcomes has not been well studied. Design/setting/participants/interventions/outcome measures: Using the American Heart Association's Get With The Guidelines Heart Failure Registry, we identified HFrEF patients presenting with acute decompensated heart failure (ADHF) and compared rates of GDMT prescription between those presenting prior to and during the pandemic. In a subgroup of patients with a concomitant COVID-19 diagnosis, we evaluated the association of prior to admission GDMT use with in-hospital mortality and severe COVID-19. Results: 23,899 patients were admitted with HFrEF during the pandemic (2/16/20-3/24/21) and 26,459 patients were admitted in the year prior (2/16/19-2/15/20). In this overall cohort, prior to admission ACEI/ARB/ARNI (45.6 % vs 48.1 %, p < 0.0001) and BB (56.9 % vs 62.4 %, p < 0.0001) use was lower among admitted HFrEF patients during the pandemic when compared to the year prior. Rates of ACEI/ARB/ARNI, MRA, and triple therapy (ACE/ARB/ARNI + BB + MRA) prescription at discharge were higher during the pandemic compared to the year prior. Among a subgroup of those with HFrEF and COVID-19 (n = 333), prior to admission GDMT use was not associated with in-hospital mortality or severe COVID-19. Conclusion: We found no association between prior to admission GDMT use and in-hospital mortality or severe COVID-19 among HFrEF patients admitted with ADHF and COVID-19. GDMT prescription at discharge for HFrEF patients overall has remained either similar or improved during the pandemic.

Protocol-driven approach to guideline-directed medical therapy optimization for heart failure: A real-world application to recovery.

The objective of our study was to evaluate the real-world effects of an aggressive, personalized protocol for guideline-directed medical therapy (GDMT) titration in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We conducted a two-center retrospective cohort study. Patients with HFrEF who presented to a HF clinic from January 2020 to December 2022 were placed on a GDMT protocol. 180 patients were included in the study. Mean GDMT score significantly increased from 4.7 to 5.9 (p < 0.001) between initial and final visits. Mean left ventricular ejection fraction (LVEF) significantly increased from 28 % to 33 % (+5 %, p < 0.001). 27 (15.7 %) of the 172 patients with complete New York Heart Association (NYHA) classification data had improvement by at least 1 class, while 2 (1.2 %) patients had worsening NYHA classification. 140 (77.8 %) patients had no unplanned hospitalizations between visits. 21 (11.7 %) patients had an unplanned hospitalization for acute HF during the study period with a mean time from first clinic visit to hospitalization of 183 days (range: 13-821 days). 2 (1.1 %) patients were hospitalized due to GDMT-associated adverse drug events (i.e. hypotension, hyperkalemia). 7 (3.9 %) patients died during the study period, which was lower than the predicted 1-year death rate for our cohort (12.3 %) using the MAGGIC score. In conclusion, an aggressive, personalized protocol for GDMT titration in patients with HFrEF led to significant improvements in LVEF, NYHA classification, hospitalization, and mortality in a real-world setting. This protocol may help serve as a road map to lessen the gap between clinical knowledge and practice surrounding optimization of GDMT and move HFrEF patients toward a path to recovery.

SGLT2 Inhibitor Therapy In Patients With Advanced Heart Failure And Reduced Ejection Fraction.

AIMS: Sodium-glucose cotransporter inhibitors (SGLT2-i) improve outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF). However, evidence in patients with advanced HF is lacking. We aimed to determine the effect of SGLT2-i in advanced HFrEF compared to their effect on a non-advanced population. METHODS: Consecutive HFrEF outpatients who started SGLT2-i were observed for 6-months. Patients were categorized as having advanced or non-advanced HFrEF. The primary outcome was the trend of NTproBNP in the two groups. Secondary outcomes included changes in New York Heart Association (NYHA) class, glomerular filtration rate (GFR), and ejection fraction (LVEF). The association between advanced HF diagnosis and including N-terminal pro-brain natriuretic peptide (NTproBNP) reduction was tested using multivariate analysis. RESULTS: Overall, 105 patients (45 advanced, 60 non-advanced) were included. Mean age was 56±10 years, 22% were female, and 35% had ischemic heart disease. Median NTproBNP at baseline for advanced and non-advanced patients was 1672pg/ml (IQR 520-3320) vs. 481 pg/ml (IQR 173-917), respectively (p<0.001). At follow-up, only non-advanced patients reduced their NTproBNP (-32% (95% CI -51 to -3), p<0.001), while advanced patients had an increase in NTproBNP. LVEF and NYHA class improved only in non-advanced patients. GFR was stable in both subgroups. At multivariate analysis a diagnosis of advanced HF was independently associated with a reduced probability of NTproBNP reduction (OR 0.041 (95% CI 0.002-0.752), p=0.031). Only one patient discontinued the drug due to side effects. CONCLUSION: In advanced HFrEF, SGLT2-i do not impact on NTproBNP, LVEF or NYHA class but are well tolerated.

Sequencing Quadruple Therapy for Heart Failure with Reduced Ejection Fraction: Does It Really Matter?

The conventional sequence of guideline-directed medical therapy (GDMT) initiation in heart failure with reduced ejection fraction (HFrEF) assumes that the effectiveness and tolerability of GDMT agents mirror their order of discovery, which is not true. In this review, the authors discuss flexible GDMT sequencing that should be permitted in special populations, such as patients with bradycardia, chronic kidney disease, or atrial fibrillation. Moreover, the initiation of certain GDMT medications may enable tolerance of other GDMT medications. Most importantly, the achievement of partial doses of all four pillars of GDMT is better than achievement of target dosing of only a couple.

Frailty and Its Implications in Heart Failure with Reduced Ejection Fraction: Impact on Prognosis and Treatment.

Frailty affects half of all patients with heart failure with reduced ejection fraction (HFrEF) and carries a ∼2-fold increased risk of mortality. The relationship between frailty and HFrEF is bidirectional, with one condition exacerbating the other. Paradoxical to their higher clinical risk, frail patients with HFrEF are more often under-treated due to concerns over medication-related adverse clinical events. However, current evidence suggests consistent safety of HF medical therapies among older frail patients with HFrEF. A multidisciplinary effort is necessary for the appropriate management of these high-risk patients which focuses on the optimization of known beneficial therapies with a goal-directed effort toward improving quality of life.

A Need to Preserve Ejection Fraction during Heart Failure.

Heart failure (HF) is a significant global healthcare burden with increasing prevalence and high morbidity and mortality rates. The diagnosis and management of HF are closely tied to ejection fraction (EF), a crucial parameter for evaluating disease severity and determining treatment plans. This paper emphasizes the urgent need to maintain EF during heart failure, highlighting the distinct phenotypes of HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). It discusses the complexities of HFrEF pathophysiology and its negative impact on patient outcomes, stressing the importance of ongoing research and the development of effective therapeutic interventions to slow down the progression from preserved to reduced ejection fraction. Additionally, it explores the potential role of renal denervation in preserving ejection fraction and its implications for HFrEF management. This comprehensive review aims to offer valuable insights into the critical role of EF preservation in enhancing outcomes for patients with heart failure.

Anthropometric measures and long-term mortality in non-ischaemic heart failure with reduced ejection fraction: Questioning the obesity paradox.

AIMS: Although body mass index (BMI) is the most commonly used anthropometric measure to assess adiposity, alternative indices such as the waist-to-height ratio may better reflect the location and amount of ectopic fat as well as the weight of the skeleton. METHODS AND RESULTS: The prognostic value of several alternative anthropometric measures was compared with that of BMI in 1116 patients with non-ischaemic heart failure with reduced ejection fraction (HFrEF) enrolled in DANISH. The association between anthropometric measures and all-cause death was adjusted for prognostic variables, including natriuretic peptides. Median follow-up was 9.5 years (25th-75th percentile, 7.9-10.9). Compared to patients with a BMI 18.5-24.9 kg/m2 (n = 363), those with a BMI ≥25 kg/m2 had a higher risk of all-cause and cardiovascular death, although this association was only statistically significant for a BMI ≥35 kg/m2 (n = 91) (all-cause death: hazard ratio [HR] 1.78, 95% confidence interval [CI] 1.28-2.48; cardiovascular death: HR 2.46, 95% CI 1.69-3.58). Compared to a BMI 18.5-24.9 kg/m2, a BMI <18.5 kg/m2 (n = 24) was associated with a numerically, but not a significantly, higher risk of all-cause and cardiovascular death. Greater waist-to-height ratio (as an exemplar of indices not incorporating weight) was also associated with a higher risk of all-cause and cardiovascular death (HR for the highest vs. the lowest quintile: all-cause death: HR 2.11, 95% CI 1.53-2.92; cardiovascular death: HR 2.17, 95% CI 1.49-3.15). CONCLUSION: In patients with non-ischaemic HFrEF, there was a clear association between greater adiposity and higher long-term mortality. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00542945.

Management of Chronic Heart Failure with Reduced Ejection Fraction.

Heart failure with reduced ejection fraction (HFrEF) is a commonly seen clinical entity in the family physician's practice. This clinical review focuses on the pharmacologic management of chronic HFrEF. Special attention is paid to the classification of heart failure and the newest recommendations from the American Heart Association concerning the use of guideline-directed medical therapy. ß blockers, ACE inhibitors, ARBs, mineralocorticoid receptor antagonists are discussed in detail. The new emphasis on sacubitril-valsartan and SGLT2i's as therapies for HFrEF are reviewed, followed by a brief discussion of more advanced therapies and comorbidity management.

Web-Based Dynamic Nomogram for Predicting Risk of Mortality in Heart Failure with Mildly Reduced Ejection Fraction.

Purpose: This study aimed to develop an integrative dynamic nomogram, including N-terminal pro-B type natural peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR), for predicting the risk of all-cause mortality in HFmrEF patients. Patients and Methods: 790 HFmrEF patients were prospectively enrolled in the development cohort for the model. The least absolute shrinkage and selection operator (LASSO) regression and Random Survival Forest (RSF) were employed to select predictors for all-cause mortality. Develop a nomogram based on the Cox proportional hazard model for predicting long-term mortality (1-, 3-, and 5-year) in HFmrEF. Internal validation was conducted using Bootstrap, and the final model was validated in an external cohort of 338 consecutive adult patients. Discrimination and predictive performance were evaluated by calculating the time-dependent concordance index (C-index), area under the ROC curve (AUC), and calibration curve, with clinical value assessed via decision curve analysis (DCA). Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were used to assess the contributions of NT-proBNP and eGFR to the nomogram. Finally, develop a dynamic nomogram using the "Dynnom" package. Results: The optimal independent predictors for all-cause mortality (APSELNH: A: angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitor (ACEI/ARB/ARNI), P: percutaneous coronary intervention/coronary artery bypass graft (PCI/CABG), S: stroke, E: eGFR, L: lg of NT-proBNP, N: NYHA, H: healthcare) were incorporated into the dynamic nomogram. The C-index in the development cohort and validation cohort were 0.858 and 0.826, respectively, with AUCs exceeding 0.8, indicating good discrimination and predictive ability. DCA curves and calibration curves demonstrated clinical applicability and good consistency of the nomogram. NT-proBNP and eGFR provided significant net benefits to the nomogram. Conclusion: In this study, the dynamic APSELNH nomogram developed serves as an accessible, functional, and effective clinical decision support calculator, offering accurate prognostic assessment for patients with HFmrEF.

Left ventricular thrombus recurrence after anticoagulation discontinuation.

Background: Evidence regarding the duration of anticoagulation (AC) therapy for left ventricular thrombus (LVT) is lacking. This study aims to evaluate the rate and risk factors for LVT recurrence in patients with Anterior ST-Segment elevation Myocardial Infarction (STEMI) complicated by LVT. Methods: This was a retrospective analysis of patients with Anterior STEMI complicated by LVT and reduced ejection fraction (<35 %) from 2010 to 2020. Patients with atrial fibrillation and hypercoagulable state were excluded. Recurrence of LVT was defined as a new LVT on transthoracic echocardiography (TTE) after interval resolution and AC discontinuation. Demographics, comorbidities, guideline directed medical therapy, TTE, and angiographic characteristics were assessed and compared in patients with and without LVT recurrence. Results: 87 patients met the inclusion criteria. Nine (10.3 %) had LVT recurrence of which three (33.3 %) had cardioembolic events. More patients with recurrence had ventricular aneurysm/scarring (33 % vs 10.3 %) and multi-vessel disease (22.2 % vs 9 %). Conclusion: This study reveals that a portion of patients with Anterior STEMI complicated by LVT are at a higher risk of recurrence after initial resolution and AC discontinuation. Larger prospective trials are needed to re-address the appropriate duration of anticoagulation.

Renin-angiotensin system inhibitors and non-ST-elevation myocardial infarction outcomes based on left ventricular ejection fraction.

BACKGROUND: We assessed left ventricular ejection fraction (LVEF) to compare the effects of renin-angiotensin system inhibitors (RASI) in patients with non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: We categorized 4558 patients with NSTEMI as either RASI users (3752 patients) or non-users (806 patients). The 3-year patient-oriented composite outcome (POCO), which included all-cause death, recurrent myocardial infarction, any repeat revascularization, or hospitalization for heart failure (HF), was the primary outcome. To compare clinical outcomes, a multivariable-adjusted hazard ratio (aHR) was calculated after performing multicollinearity tests on all significant confounding variables (P < 0.05). RESULTS: Among RASI users, the aHRs for POCO, all-cause death, and cardiac death were significantly higher in the HF with reduced EF (HFrEF) subgroup than in the HF with mildly reduced EF (HFmrEF) (1.610, 2.120, and 2.489; P < 0.001, <0.001, and <0.001; respectively) and HF with preserved EF (HFpEF) (2.234, 3.920, and 5.215; P < 0.001, <0.001, and <0.001; respectively) subgroups. The aHRs for these variables were significantly higher in the HFmrEF subgroup than the HFpEF subgroup (1.416, 1.843, and 2.172, respectively). Among RASI non-users, the aHRs for these variables were significantly higher in the HFrEF subgroup than the HFmrEF (2.573, 3.172, and 3.762, respectively) and HFpEF (2.425, 3.805, and 4.178, respectively) subgroups. In three LVEF subgroups, RASI users exhibited lower aHRs for POCO and all-cause death than RASI non-users. CONCLUSION: In the RASI users group, the aHRs for POCO and mortality were highest in the HFrEF subgroup, intermediate in the HFmrEF subgroup, and lowest in the HFpEF subgroup.

Beta-blocker use and outcomes in patients with heart failure and mildly reduced and preserved ejection fraction.

AIMS: In the absence of randomized trial evidence, we performed a large observational analysis of the association between beta-blocker (BB) use and clinical outcomes in patients with heart failure (HF) and mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF). METHODS AND RESULTS: We pooled individual patient data from four large HFmrEF/HFpEF trials (I-Preserve, TOPCAT, PARAGON-HF, and DELIVER). The primary outcome was the composite of cardiovascular death or HF hospitalization. Among the 16 951 patients included, the mean left ventricular ejection fraction (LVEF) was 56.8%, and 13 400 (79.1%) had HFpEF (LVEF ≥50%). Overall, 12 812 patients (75.6%) received a BB. The median bisoprolol-equivalent dose of BB was 5.0 (Q1-Q3: 2.5-5.0) mg with BB continuation rates of 93.1% at 2 years (in survivors). The unadjusted hazard ratio (HR) for the primary outcome did not differ between BB users and non-users (HR 0.98, 95% confidence interval [CI] 0.91-1.05), but the adjusted HR was lower in BB users than non-users (0.81, 95% CI 0.74-0.88), and this association was maintained across LVEF (pinteraction = 0.88). In subgroup analyses, the adjusted risk of the primary outcome was similar in BB users and non-users with or without a history of myocardial infarction, hypertension, or a baseline heart rate <70 bpm. By contrast, a better outcome with BB use was seen in patients with atrial fibrillation compared to those without atrial fibrillation (pintreraction = 0.02). CONCLUSIONS: In this observational analysis of non-randomized BB treatment, there was no suggestion that BB use was associated with worse HF outcomes in HFmrEF/HFpEF, even after extensive adjustment for other prognostic variables.

County-Level Variation in Triple Guideline-Directed Medical Therapy in Heart Failure With Reduced Ejection Fraction.

Background: Current guidelines recommend simultaneous initiation of multidrug guideline-directed medical therapy classes for heart failure with reduced ejection fraction. Objectives: The purpose of this study was to evaluate county-level variation in use of triple guideline-directed medical therapy, defined as simultaneous prescription fills for beta-blockers, renin-angiotensin system inhibitors or angiotensin receptor neprilysin inhibitors, and mineralocorticoid receptor antagonists, in heart failure with reduced ejection fraction. Methods: We conducted a cohort study using Medicare Fee-for-Service claims data (parts A, B, and D between 2013 and 2019). Features of counties including area-level indicators of poverty, employment, and educational attainment and aggregated patient-level sociodemographic and medical history variables were compared by quintiles of triple therapy use. A multilevel logistic regression model was constructed to estimate the contextual effect of clustering by counties, which was expressed as a median OR. Results: 304,857 patients from 2,600 counties (83% of all U.S. counties) were included. The median for triple therapy use was 14.3% (IQR: 10.3%-18.8%) across included counties with a wide variation (range: 0%-54.5%). Compared to counties in the highest use quintile, counties in lowest triple therapy use quintile had worse area-level indicators of socioeconomic status (% unemployment 6.8% vs 6.2%). Counties in lowest quintile had higher proportion of Black patients (13.3% vs 5.7% in highest quintile) and patients with low-income subsidy (29.3% vs 25.8% in highest quintile). The median OR was 1.30 (95% CI: 1.28-1.33). Conclusions: We observed variation in triple therapy use across counties in the United States with suboptimal local use patterns correlating with indicators of socioeconomic disadvantage.

Determinants of Guideline-Directed Medical Therapy Implementation During Heart Failure Hospitalization.

Background: Despite evidence that guideline-directed medical therapies (GDMTs) improve outcomes in patients with heart failure (HF) with reduced ejection fraction (HFrEF), implementation remains suboptimal. Objectives: The purpose of this study was to measure GDMT implementation during acute HFrEF hospitalization, evaluate the association between socioeconomic factors and GDMT implementation, and assess the association of GDMT utilization with subsequent clinical events. Methods: Retrospective determination of GDMT utilization using a modified optimal medical therapy (mOMT) score (which accounts for specific contraindications to drugs) during unplanned HF hospitalization of consecutive adult patients with new-onset or previously diagnosed HFrEF from 2017 to 2018. Outcomes included discharge mOMT score, association between socioeconomic factors and GDMT implementation (assessed using both the Mann-Whitney U test for binary variables and the Kruskall-Wallace for nonbinary variables), composite outcome 1-year all-cause mortality and 1-year HF readmission, and each component as a function of discharge mOMT score (assessed using univariate and multivariable Cox proportional hazards regression models). Results: Of 391 patients fulfilling entry criteria (of which 152 [38.9%] had new-onset HFrEF), only 49 (12.5%) had a perfect or near-perfect discharge mOMT score. Black patients and those experiencing homelessness had significantly lower discharge mOMT scores. Higher discharge mOMT score is associated with a lower rate of composite endpoint events, particularly in patients with new-onset HFrEF. Overall, a 0.1-increase in the mOMT score resulted in a 9.2% reduction in the composite endpoint. Conclusions: Suboptimal implementation of GDMT during HF hospitalization is widespread and is associated with a worse outcome. Black patients and patients experiencing homelessness were less likely to have GDMT optimized.

Trajectory of Irisin as a Predictor of Kidney-Related Outcomes in Patients with Asymptomatic Heart Failure.

The purpose of the study is to elucidate whether irisin is a promising predictive biomarker for kidney-related events in patients with T2DM and concomitant asymptomatic HF. We prospectively enrolled 146 T2DM patients who had either evidence of structural cardiac abnormality or elevated levels of N-terminal brain natriuretic pro-peptide (NT-proBNP) > 125 pmol/mL and followed them for 52 weeks. Structural cardiac abnormalities were used as the minimum from the following criteria: abnormal left ventricular (LV) global longitudinal strain (GLS) < -16%, LV hypertrophy, left atrial volume index > 34 mL/m2, abnormal ratio of early transmitral diastolic filling velocity/early mitral annular velocity ≥ 13 units. All the patients underwent echocardiographic and Doppler examinations by two blinded, highly experienced echocardiographers. NT-proBNP, irisin, TNF-alpha, and hs-CRP were quantified in the serum at baseline, at 26 weeks, and at the end of the study. The kidney-related outcomes consisted of an eGFR reduction by 40% from baseline, or end-stage kidney disease, or kidney replacement therapy. We found that levels of irisin at baseline < 4.15 ng/mL and/or its decrease > 20% from baseline in T2DM patients predicted kidney-related events better than baseline levels/dynamic NT-proBNP and the use of SGLT2 inhibitors. In conclusion, we established that a low baseline level of irisin and its 20% decrease correlated with newly kidney-related events in T2DM patients with asymptomatic HFpEF/HFmrEF.

Epicardial adipose tissue volume and density are associated with heart failure with improved ejection fraction.

BACKGROUND: Heart failure (HF) with improved ejection fraction (EF, HFimpEF) is a distinct HF subtype, characterized by left ventricular (LV) reverse remodeling and myocardial functional recovery. Multiple cardiometabolic factors are implicated in this process. Epicardial adipose tissue (EAT), emerging as an endocrine and paracrine organ, contributes to the onset and progression of HF. However, the relation between EAT and the incidence of HFimpEF is still unclear. METHODS: A total of 203 hospitalized HF patients with reduced EF (HFrEF, LVEF ≤ 40%) who underwent coronary CT angiography (CCTA) during index hospitalization were consecutively enrolled between November 2011 and December 2022. Routine follow-up and repeat echocardiograms were performed. The incidence of HFimpEF was defined as (1) an absolute LVEF improvement ≥ 10% and (2) a second LVEF > 40% (at least 3 months apart). EAT volume and density were semiautomatically quantified on non-enhanced series of CCTA scans. RESULTS: During a median follow-up of 8.6 (4.9 ~ 13.3) months, 104 (51.2%) patients developed HFimpEF. Compared with HFrEF patients, HFimpEF patients had lower EAT volume (115.36 [IQR 87.08 ~ 154.78] mL vs. 169.67 [IQR 137.22 ~ 218.89] mL, P < 0.001) and higher EAT density (-74.92 ± 6.84 HU vs. -78.76 ± 6.28 HU, P < 0.001). Multivariate analysis showed lower EAT volume (OR: 0.885 [95%CI 0.822 ~ 0.947]) and higher density (OR: 1.845 [95%CI 1.023 ~ 3.437]) were both independently associated with the incidence of HFimpEF. Subgroup analysis revealed that the association between EAT properties and HFimpEF was not modified by HF etiology. CONCLUSIONS: This study reveals that lower EAT volume and higher EAT density are associated with development of HFimpEF. Therapies targeted at reducing EAT quantity and improving its quality might provide favorable effects on myocardial recovery in HF patients.

Optimal Medical Therapy and Outcomes Among Patients With Chronic Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Optimal medical therapy (OMT) scoring may stratify clinical risk in real-world chronic heart failure with reduced ejection fraction (HFrEF) by integrating use and dosing of guideline-directed medical therapy (GDMT) for HFrEF. OBJECTIVES: The purpose of this study was to characterize patients and associated long-term clinical outcomes by OMT score-derived treatment groups. METHODS: CHAMP-HF (Change the Management of Patients with Heart Failure) included U.S. outpatients with chronic HFrEF receiving ≥1 GDMT. OMT subgroups were defined as suboptimal (score <3), acceptable (score = 3), and optimal (score ≥4) by baseline use and dose of GDMT, as proposed by the HF Collaboratory consortium. Cox proportional hazard analyses were used to assess for all-cause and cardiovascular death across subgroups, after adjusting for demographic and clinical covariates. RESULTS: The authors studied 4,582 participants enrolled in CHAMP-HF with available 2-year follow-up. Median age was 68 years, 1,327 (29%) were women, and 2,842 (62%) were White, non-Hispanic. Median OMT score across the population was 4 (Q1-Q3: 2-5), and 1,628 (35%) had suboptimal, 665 (14%) had acceptable, and 2,289 (50%) had optimal therapy. Participants with optimal treatment were younger, had higher annual household income, and were enrolled from practices with dedicated HF clinics (all P < 0.001) than participants with acceptable or suboptimal treatment. Participants with optimal treatment had lower all-cause death (adjusted HR: 0.77; 95% CI: 0.64-0.92) and cardiovascular death (adjusted HR: 0.79; 95% CI: 0.65-0.96) than those with suboptimal treatment. CONCLUSIONS: Across a large cohort of chronic ambulatory HFrEF, OMT scores stratified risk of all-cause and cardiovascular death.

A Rare Case of Cephalosporin Anaphylaxis-Induced Reverse Takotsubo.

This case report details an unusual occurrence of reverse takotsubo induced by cefazolin anaphylaxis. While anaphylactic reactions typically manifest with hypotension and bronchospasm, the development of takotsubo is a rare outcome. The patient experienced an episode of cefazolin-induced anaphylaxis during elective shoulder surgery, subsequently developing reverse takotsubo cardiomyopathy (rTTC) during her hospitalization. Initial testing showed a reduced heart function, with an ejection fraction (EF) dropping to 32% from a previously normal EF exceeding 50%. However, a follow-up heart catheterization three weeks later revealed a return to normal heart function. The patient received appropriate management for heart failure. By emphasizing the nuanced features and symptoms, we aim to enhance the recognition and management of this condition. Sharing such cases contributes to the medical community's knowledge and facilitates the advancement of strategies for diagnosing and managing anaphylaxis-induced reverse takotsubo.