bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic impact of thyroid dysfunction in patients with incident heart failure: a nationwide study
Authors: Petersen J , Yafasova A , Bager L G V , Ali S A , Kristensen S L , Rorth R , Selmer C , Kober L , Fosbol E , Ostergaard L
Published: November 2023

Background

Thyroid hormones directly affect the cardiovascular system. Thyroid dysfunction can cause a variety of haemodynamic alterations and has been associated with an increased risk of atrial fibrillation (AF), heart failure (HF), and all-cause mortality. However, a paucity remains regarding knowledge on the prognostic impact of thyroid dysfunction in patients with HF.

Purpose

To examine the impact of the whole spectrum of thyroid dysfunction in patients with HF on the associated risk of AF, HF admissions, and all-cause mortality.

Methods

This Danish cohort study included patients with a first-time HF diagnosis from 2000–2021. According to blood samples within 6 months prior to the HF diagnosis, the study population was categorized based on thyroid function in 1) overt hypothyroidism, 2) subclinical hypothyroidism, 3) euthyroidism, 4) subclinical hyperthyroidism, and 5) overt hyperthyroidism. With up to one year of follow-up from the date of HF diagnosis, we used Aalen-Johansen estimator to examine the cumulative incidence frequency (CIF) of AF and HF admissions and Kaplan-Meier estimates to assess all-cause mortality. Multivariable Cox proportional hazard analysis was performed to investigate differences in outcomes among groups.

Results

Of the 7,380 individuals included in this study (56.6% female, median age 76.5 years [p25-p75: 67.9-84.1]), 102 (1.4%) had overt hypothyroidism, 1,706 (23.1%) had subclinical hypothyroidism, 4,374 (59.3%) were euthyroid, 691 (9.4%) had subclinical hyperthyroidism, and 507 (6.9%) had overt hyperthyroidism. Compared with euthyroid patients, the adjusted one-year hazard ratio (HR) for AF was 0.77 (95% CI, 0.49-1.20) for overt hypothyroidism, 1.01 (95% CI, 0.90-1.13) for subclinical hypothyroidism, 1.18 (95% CI, 1.01-1.38) for subclinical hyperthyroidism, and 1.19 (95% CI, 1.01-1.39) for overt hyperthyroidism (Figure). The adjusted one-year HR for HF hospitalizations was 1.51 (95% CI, 1.06-2.14) in patients with overt hypothyroidism, 1.07 (95% CI, 0.96-1.20) in patients with subclinical hypothyroidism, 0.99 (95% CI, 0.84-1.16) in patients with subclinical hyperthyroidism, and 1.26 (95% CI, 1.06-1.50) in patients with overt hyperthyroidism. The adjusted one-year HR for mortality was 1.81 (95% CI, 1.25-2.63) in patients with overt hypothyroidism, 1.25 (95% CI, 1.10-1.42) in patients with subclinical hypothyroidism, 1.15 (95% CI, 0.96-1.37) in patients with subclinical hyperthyroidism, and 1.46 (95% CI, 1.20-1.78) in patients with overt hyperthyroidism.

Conclusion

In patients with HF, overt and subclinical hyperthyroidism was associated with an increased rate of AF. Both hypo and hyperthyroid states were associated with increased risk of HF admission and mortality. Increased awareness regarding thyroid status in patients with HF is warranted.
Non-invasive measurement of global myocardial work to predict all-cause death and heart failure hospitalization in non-ischemic cardiomyopathy
Authors: Rodenas-Alesina E , Lozano Torres J , Badia C , Tobias P , Vila R , Calvo M , Casas-Masnou G , Cesareo M , Giustiniani A , Fernandez-Galera R , Soriano-Colome T , Olivella A , Mendez-Fernandez A B , Ferreira-Gonzalez I , Rodriguez-Palomares J F
Published: November 2023

Background

Global myocardial work (GMW) can be non-invasively calculated using a dedicated software using global longitudinal strain (GLS) and blood pressure. The prognostic value of GMW in patients with non-ischemic cardiomyopathy (NICM) has not yet been demonstrated.

Purpose

To stablish the prognostic significance of GMW in NICM.

Methods

Patients with NICM with an available echocardiogram between 2015 and 2019 and left ventricular ejection fraction (LVEF) <50% were retrospectively included. A dedicated software was used to analyze GMW, global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE). All quantitative variables were modelled as a spline with three knots to account for non-linear associations. Patients were followed up until the occurrence of death, heart failure hospitalization or lost to follow-up. The primary endpoint was a composite of all-cause death of heart failure hospitalization (HFH).

Results

A total of 524 patients with NICM in whom GMW analysis was feasible were included in the study. Median LVEF was 35 (IQR 27 – 42), and median GMW was 968 (IQR 670 – 1282). There were no significant differences in clinical characteristics between patients with GMW above or below median, except for higher rates of HFH during the previous year in patients with lower GMW. Patients with lower GMW displayed lower LVEF, greater LV dilatation, worse GLS, lower TAPSE and a higher E/e’ ratio (Table 1). GMW and GCW were significantly collinear with GLS (Pearson’s r = -0.85 and -0.83 respectively, p<0.001), GWE was moderately collinear (Pearson’s r = -0.64, p<0.001) whereas GWW was not (Pearson’s r = 0.05, p = 0.23). During a median follow-up of 4.8 years, 164 (31.3%) patients presented the primary endpoint. After adjusting for age, LVEF, end-diastolic volume and TAPSE, GMW showed a significant, non-linear association with the primary endpoint (Figure 1), at the expense of both death and HFH when separately analyzed. Risk progressively increased with a GMW below 2500 mmHg% and plateaued at 1000 mmHg%. Only GCW retained an association with the primary outcome like the one observed with GMW, whereas GWW and GWE did not. Adding GMW to the model led to an improved risk discrimination (AUC increased from 0.66 to 0.69, p = 0.043).

Conclusions

Global myocardial work and GCW are new independent echocardiographic predictors of all-cause death and HFH in NICM, with higher rates of the outcome at lower GMW and GCW values, whereas GWW and GWE were not associated with event rates in NICM.
Level of education and mortality in the vulnerable period following an acute heart failure hospitalization
Authors: Pereira Da Cunha G , Melo L H S , Neto J D , Duarte M B , Moretti R , Vercka K , Senger C R , Pain J R , Silvestre O , Nadruz W , Matos L G , Adam E L , Cirino R D , Taniguchi F B , Fernandes-Silva M M
Published: November 2023

Introduction

Patients hospitalized for acute heart failure (HF) are at increased risk of death in the early post-discharge period, so-called the "vulnerable period" (1). Post-discharge treatment strategies can help improve outcomes, but the role of the patient's level of education on this regard is unclear.

Purpose

To analyse the association between level of education and 180-day mortality after discharge from acute HF hospitalization.

Methods

We performed a prospective cohort study of patients who were discharged alive following hospitalization for acute HF in 26 hospitals in Brazil from February 2016 and September 2021. Patients were classified according to the International Standard Classification of Education 2011 into four groups: Less than Basic, Basic, Intermediate and Advanced. We analysed all-cause mortality in the 180 days following hospital discharge using Cox regression.

Results

We evaluated 2724 patients (mean age 61±15 years; 42% women) hospitalized for acute HF, who were divided according to education level: less than basic (n = 280, 10%), basic (n = 1503, 55%), intermediate (n = 716, 26%) and advanced (n = 225, 8%). Patients with lower education levels were older (68±12 vs 62±14 vs 56±16 vs 58±15 years, p-for-trend<0.001), more frequently women (47% vs 43% vs 40% vs 37%, p-for-trend = 0.005) and non-whites (77% vs 66% vs 65% vs 53%, p-for-trend<0.001), compared with those with higher education levels. At discharge, a prescription of both angiotensin-converting enzyme inhibitors /angiotensin receptor blockers, beta-blocker and mineralocorticoid receptor antagonists (41% vs 45% vs 49% vs 53%, p-for-trend = 0.001), vaccine counselling (52% vs 50% vs 55% vs 62%, p-for-trend = 0.002) and weigh management counselling (72% vs 69% vs 72% vs 81%, p-for-trend = 0.007) were less frequently provided for patients with lower education. Education level was inversely associated with the risk of death in the follow-up period (Hazard ratio (HR) 0.71, 95%CI 0.61 – 0.84, p = <0.001; Figure). This association remained significant after adjusting for baseline characteristics (age, sex, race, left-ventricle ejection fraction, previous HF, HF aetiology, cardiac resynchronization therapy/implantable cardiac defibrillator use, chronic kidney disease and income) and prescription of disease-modifying drugs, vaccine and weight management counselling at discharge (adjusted HR 0.78, 95% CI 0.64 – 0.95, p = 0.011).

Conclusion

In this large cohort of patients discharged after hospitalization for acute HF, lower education levels were independently associated with higher mortality rates in the vulnerable period.
Sex differences in long-term outcomes among hospitalized heart failure patients across the spectrum of ejection fraction: findings from the Get with the guidelines - heart failure registry
Authors: Keshvani N , Shah S , Ayodele I , Chiswell K , Alhanti B , Allen L , Sharma K , Greene S , Yancy C , Van Spall H , Fonarow G , Heidenreich P , Pandey A
Published: November 2023

Background

Sex differences in 5-year outcomes across heart failure (HF) ejection fraction (EF) subtypes are not well known.

Purpose

To assess the interaction between sex and EF for risk of long-term adverse outcomes after hospitalization with HF.

Methods

Patients from American Heart Association’s Get With The Guidelines – Heart Failure registry enrolled between 1/1/2006 – 12/31/2014 with age ≥ 65 years with available 5-year follow-up data, ascertained through linkage with Medicare fee-for-service Part A administrative claims, were included. HF subtypes included HF with reduced EF (HFrEF) with EF ≤ 40%, HF with mildly reduced EF (HFmrEF) with EF 41-49%, and HF with preserved EF (HFpEF) with EF ≥ 50%. Sex differences in 5-year all-cause mortality and readmission for each HF subtype were assessed using unadjusted cumulative incidence methods and adjusted Cox models. Median survival across HF subtypes was compared to median survival of U.S. adults.

Results

155,670 patients (mean age 81 years, 53.4% females) were included. Male patients were younger and had a higher prevalence of prior myocardial infarction or coronary artery bypass graft surgery and were more likely to have HFrEF, while women were more likely to have history of hypertension and HFpEF. The median post-hospitalization survival of patients with HF was substantially lower than the age- and sex-specific U.S. life expectancy across each HF subtype (Figure 1).Patients with HF had high 5-year mortality rates (HFrEF male: 81.3%, female: 78.4%; HFpEF male: 80.5% vs female 79.5%). In adjusted analysis, female (vs. male) patients had a significantly lower 5-year mortality risk (HR [95%CI]: 0.89 [0.87 – 0.90], p<0.01) and a higher 5-year readmission risk (all-cause: 1.03 [1.02 – 1.04]), CV: 1.05 [1.04 – 1.07]), HF: 1.06 [1.04 – 1.08], p<0.01 for each). HF subtype modified the association between sex and 5-year outcomes (pinteraction <0.05 for mortality and CV and HF readmission), with the greatest risk reduction of mortality for female vs. male patients with HFrEF and the greatest risk increase of readmission (CV and HF) among female vs. male patients with HFmrEF and HFpEF (Figure 2).

Conclusion

Among patients with HF, the overall survival post-HF hospitalization is very low for each HF subtype. Female patients have a lower 5-year mortality risk but a higher risk of HF or CV readmission regardless of EF.Figure 1Figure 2
Usefulness of Neutrophil-to-Lymphocyte Ratio (NLR) in predicting adverse outcomes in adult patients with heart failure : A systematic review and meta analysis
Authors: Mondal A , Patel B , Pingili A , Katukuri N , Bhanushali A , Vyas A , Jain A , Desai R
Published: November 2023

Background

Inflammation plays a potential role in heart failure (HF) etiology and prognosis. Neutrophil-to-Lymphocyte ratio (NLR) is a simple, routinely available lab criteria. In this meta-analysis, we sought to investigate the role of NLR on HF outcomes which remains unexplored.

Methods

PubMed, Embase and Scopus were systematically screened to find studies through August 2022, reporting data on association of HF related outcomes [all-cause mortality (ACM), cardiovascular (CV) death, in-hospital, HF readmissions and composite events] and NLR. Random effects models and I2 statistics were used to estimate pooled odds of outcomes and heterogeneity. Leave one out sensitivity analysis was performed.

Results

A total of 11 studies (6 retrospective and 5 prospective, 4 studies from Asia and Europe each, 2 from the US and 1 multicenter study) including 12954 patients (mean age: 69 years, Males 57.2%) from 2011 to 2022 with an average follow up duration of 54.8 months were included. Elevated NLR was significantly associated with ACM (aOR 1.80, 95%CI 1.46-2.22, p<0.01, Table 1), HF readmissions (aOR 2.53, 95% CI 1.60-3.99), in-hospital mortality (aOR 3.26, 95% CI 1.76- 6.02), CV mortality (aOR 1.84, 95%CI 1.03-3.31) and composite CV outcome including heart transplant (OR 2.07, 95% CI 1.32-3.25), p<0.001.

Conclusion

Elevated NLR was significantly associated with worse outcomes in HF patients. The NLR test might potentially be useful in identifying high-risk HF patients and curtail worse outcomes.
Impact of eGFR slope upon mortality in a real world heart failure cohort
Authors: Moya A , Oeste C , Beles M , Masuy I , Verstreken S , Dierckx R , Heggermont W , Goethals M , Bartunek J , Vanderheyden M
Published: November 2023

Background

Heart failure (HF) frequently causes an imbalance in heart and kidney functions, and the prognosis of heart and kidney disease can worsen one another. In addition to the prognostic role of chronic kidney disease (CKD), dynamic changes in renal function have been recognized to portend a poor prognosis in HF patients.

Purpose

This study aimed to investigate the prevalence of impaired renal function at HF diagnosis and its association with short and long-term outcomes in a real-world cohort of HF patients. In addition, we assessed how dynamic changes in renal function after HF diagnosis might predict HF prognosis.

Methods

Using a natural language processing algorithm, clinical data of patients with at least one diagnosis of HF (index event) were retrospectively collected. Patients for which the most recent estimated glomerular filtration rate (eGFR) value prior to the index date was ≤ 60 mL/min/1.73m2 and/or had a documented medical history of CKD (including dialysis) were considered as having CKD. A linear mixed effects model was used to show the longitudinal eGFR trajectories during the follow-up period (after index). A Cox proportional hazard model was used to analyse the association between baseline variables and mortality. Finally, joint modelling was used to combine the linear mixed eGFR sub-model with the survival sub-model, to estimate the effect of the current eGFR value and the eGFR slope of the year prior on mortality.

Results

The study population consisted of 1992 patients with a mean (±SD) age of 74.8 ± 11.7 years and 58% males. In total, 17% had HF with preserved ejection fraction (HFpEF, n = 339) and 70% (n = 1156) presented CKD at the index event. The median follow-up time was 3.16 years and 13% (n = 198) of the patients were deceased after two years. The group of 2-year survivors had significantly lower proportion of CKD at index (55 vs 76%, p < 0.001). The calculated mean yearly decrease of the eGFR value was 4.2 mL/min/1.73m². The multivariate Cox PH model identified age, CVA, diastolic blood pressure, HDL, and log10proBNP as baseline predictors of mortality. Joint modelling showed that a 10 mL/min/1.73m2 lower current eGFR value amongst patients was associated with an increased mortality hazard of 1.30 ± 0.06 (p < 0.001). Additionally, a decrease of 10 mL/min/1.73m2 in eGFR during the year prior indicated an increased mortality hazard of 1.87 ± 0.19 (p < 0.001).

Conclusion

In a real-world cohort of HF patients, the prevalence of CKD is high and CKD is an independent predictor of mortality. The current eGFR value and the year prior’s eGFR slope adds additional prognostic information and helps to better fine tune the individual mortality hazard. Based on the findings of this analysis, patients with worse prognosis might benefit from a closer and more vigilant follow-up.
Effect of timely availability of TTR-stabilizing therapy on diagnosis, treatment initiation, and cardiovascular outcomes in transthyretin amyloid cardiomyopathy
Authors: Dobner S , Stortecky S , Wiedemann S , Kassar M , Pilgrim T , Graeni C , Hunziker L , Bernhard B
Published: November 2023

Background

Transthyretin-stabilization reduces cardiovascular morbidity and mortality in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Despite increased access, regional differences in the availability of therapy continue to exist, and how these may affect diagnostic efficacy and cardiovascular outcomes is currently unknown.

Objective

To determine how access to and availability of tafamidis affected time-to-diagnosis, time-to-therapy, and cardiovascular outcomes in patients with ATTR-CM.

Methods and Results

91 consecutive patients diagnosed with ATTR-CM between June 2019 and June 2021 were evaluated for TTR-stabilizing therapy with tafamidis. Access was regulated by an expanded access program for the initial 42 patients (early cohort; 46.2%), while insurance coverage was required for the latter 49 patients (facilitated access cohort, 53.8%) after local regulatory drug approval in April 2020. Tafamidis was started in 37 of 42 (88.1%), and 43 of 49 patients (87.8%), respectively. Baseline characteristics, e.g., age (76.3±6.4 vs. 77.3±6, p = 0.45), sex (male: 95.2% vs. 93.9%) and ATTR-CM disease stage (≤stage 2: 88.2% vs. 90.9%, p= 0.919) were comparable between both groups.

Timely availability of tafamidis after April 2020 numerically reduced time from first presentation to diagnosis (median [months (IQR)]) from 6.2 (1.3;28.9) to 2.4 (0.7; 21.7) months (p = 0.196) and from presentation to therapy from 24.4 (10.7;46.8) to 11.8 (6.4; 32.4) months (p = 0.127). While RV function assessed by echocardiography significantly decreased in the early cohort between diagnosis and therapy initiation (S’ velocity 10±2.2 to 9.2±2.2 cm/s; p = 0.018; TAPSE 17.3±4.7 to 15.7±3.9, p = 0.008) it remained stable in the facilitated access cohort (S’ velocity 9.56±2.57 to 9.36±2.28 cm/s; p = 0.83; TAPSE 15.6±4.2 to 16.3±3.1, p = 0.45). After a median follow-up 42.3 and 24.9 months in the early and facilitated access cohort, respectively, timely availability of tafamidis in the facilitated access cohort was associated with a significant reduction of annual heart failure hospitalisations (treated: 0.12±0.34 vs. 0.5±1, p = 0.049; overall cohort: 0.17±0.37 vs. 0.35±0.47, p = 0.044). Overall, timely diagnosis of ATTR-CM within 12 months of first presentation was associated with a significant reduction in all-cause mortality [HR = 3.490 (95% CI 1.37 to 8.91), p = 0.009], prolonged survival without MACE [HR = 2.50 (95% CI 1.30 to 4.81), p = 0.006] or heart failure hospitalisation [HR = 2.52 (95% CI 1.24 to 5.16), p = 0.011].

Conclusions

Availability of tafamidis numerically shortened time-to-diagnosis and time-to-therapy initiation in ATTR-CM patients. Timely diagnosis and initiation of therapy was associated with a reduction in all-cause mortality and heart failure hospitalisations.Door-to-diagnosis-therapyClinical outcomes
Lower incidence of new-onset heart disease following covid-19 compared to viral pneumonia despite more echocardiography
Authors: Ovrebotten T , Tholin B , Myhre P L , Stavem K
Published: November 2023

Background

Studies have shown an increased risk of cardiac disease and dysfunction following COVID-19. However, it remains unknown whether infection with COVID-19 differs from other viral pneumonias with respect to subsequent incident heart disease.

Purpose

To determine the incidence of heart disease and use of cardiac procedures in patients following a diagnosis of COVID-19 compared to other viral pneumonias.

Methods

In a retrospective, observational study, we compared incidence rates for cardiac disease diagnosed after hospitalization with COVID-19 February-November 2020 versus hospitalization with viral pneumonia as the main diagnosis in 2018-2019. Data was obtained from The Norwegian Patient Registry and the Norwegian Surveillance System for Communicable Diseases, and linked with a unique national person identification number. We defined heart disease using ICD-10 codes and used Cox regression models to compare the hazard of first episodes of myocarditis, acute myocardial infarction, atrial fibrillation/flutter, heart failure, ischemic disease, other cardiac disease, and total heart disease (any of these conditions). Patients were followed until 31 December 2020, with censoring on this date or a maximum of 274 days after hospital admission.

Results

Patients hospitalized with COVID-19 in 2020 (n = 2,359) were younger, mean 59 (SD 18) vs 69 (19) years, had fewer comorbidities, had fewer hospitalizations prior to the index hospitalization (0.5 (1.2) vs 0.9 (1.8)), were more frequently treated with respiratory support (14.2% vs 7.8%) and had higher in-hospital mortality (6.9% vs 2.3%) than patients hospitalized with viral pneumonia in 2018-2019 (n = 9,018). Patients hospitalized with COVID-19 had a lower crude incidence of new total heart disease than those with viral pneumonia (56 [95%CI 48-65] vs 75 [95%CI 71-79] per 100,000 person-years). This difference persisted after adjusting for age, sex, Charlson comorbidity score (comprising age, sex, and 17 dichotomized comorbidities), hospital admission during the previous year, respiratory support, and a propensity score for being hospitalized for COVID-19 vs. other pneumonia: Hazard ratio (HR) 0.79 [95%CI 0.67-0.94], p = 0.006. Patients with COVID-19 more frequently underwent echocardiography: HR 1.41 [1.23-1.63], p = <0.001 (Fig. 1).

Conclusion

Following hospitalization for COVID-19, the incidence of total heart disease and heart failure was lower than for patients hospitalized with viral pneumonia, despite more frequent examinations with echocardiography.Figure 1
Importance of early diagnosis and treatment of heart failure across the spectrum of ejection fraction
Authors: Wang H , Gao C , Guignard-Duff M , Cole C , Hall C , Larman M , Baruah R , Gao H , Mamza J B , Lang C C , Mordi I
Published: November 2023

Introduction

Early diagnosis of heart failure (HF) is crucial in ensuring that optimal guideline-directed medical therapy (GDMT) is administered to reduce morbidity and mortality. Limited access to echocardiography could lead to late diagnosis for patients, for example during a HF hospitalisation (hHF).

Purpose

The study aimed to compare the incidence and outcomes of inpatient versus outpatient diagnosis of HF across the ejection fraction (EF) spectrum.

Methods

Electronic health records were linked to echocardiography data between 2016 to 2021. Diagnosis of incident HF was classified into inpatient (hHF) or outpatient (echocardiography reporting impaired left ventricular function or preserved EF with at least 2 continuous prescriptions of loop diuretics) and stratified by EF to define HF with reduced/mildly reduced/preserved EF (HFrEF/HFmrEF/HFpEF). A non-HF comparator group with normal LV function was also defined. The primary outcome was time to CV death or hHF.

Results

5251 individuals were identified, 1100 HFrEF, 650 HFmrEF, 1252 HFpEF, 1295 HF with unknown EF, and 954 non-HF comparators. Median duration of follow-up was 2.4 years. CV death or hHF were observed in 605 individuals (55%) with HFrEF, 237 (36%) with HFmrEF, 333 (27%) with HFpEF, 98 (10%) of non-HF comparators, and 647 (50%) with HF but unknown EF. Compared to non-HF individuals, HF patients had significantly worse outcome (hazard ratio [HR] adjusted for age and sex – HFrEF: 8.22 [95% CI: 6.64 – 10.18], p < 0.001; HFmrEF: 4.40 [3.47 – 5.58], p < 0.001; HFpEF: 2.89 [2.31 – 3.62], p < 0.001; HF with unknown EF: 8.22 [6.64 – 10.18], p < 0.001). Of the 4297 HF patients, 2318 (54%) were diagnosed as inpatients, an increase from 42% in 2016 to 62% in 2021. Those diagnosed as inpatients had significantly worse outcome than those diagnosed as outpatients (adjusted HR: 1.83 [1.66 – 2.01], p < 0.001). This difference was driven by those with HFpEF (adjusted HR: 2.31 [1.80 – 2.96], p < 0.001), but was not seen in HFrEF (1.05 [0.89 – 1.23], p = 0.554) or HFmrEF (0.97 [0.73 – 1.28], p = 0.811). For HFrEF patients first diagnosed as inpatients, those discharged on GDMT had a reduced incidence of the primary outcome: adjusted HR compared to those discharged on no GDMT drugs - monotherapy 0.77 [0.51 - 1.16], p = 0.205; dual-therapy 0.57 [0.37 – 0.88], p = 0.011; and triple therapy 0.54 [0.33 – 0.90], p = 0.017.

Conclusion

Individuals whose first presentation of HF was a HF hospitalisation had a significantly worse outcome than those who were diagnosed in the community. These real-world data also demonstrate the benefit of early optimisation of GDMT during a hHF. Our results highlight the importance of improving diagnostic pathways to allow for earlier identification and treatment of HF across the ejection fraction spectrum.Outcomes Based on Diagnostic LocationImpact of GDMT After Hospitalisation
Impact of integrated care in patients with heart failure with reduced ejection fraction: a report from the WARCEF trial
Authors: Proietti M , Romiti G F , Bonini N , Corica B , Mei D A , Qian M , Thompson J L P , Homma S , Lip G Y H
Published: November 2023

Background

In recent years there has been more and more attention to the concept of ‘integrated care’ for patients with cardiovascular diseases. Integrated care strategies have been thought to provide comprehensive evaluation and management of patients characterized by complex chronic conditions and high prevalence of comorbidities.

Purpose

To propose and evaluate an integrated care management for patients with heart failure with reduced ejection fraction (HFrEF).

Methods

We performed a secondary analysis of the WARCEF trial, which randomized HFrEF patients with sinus rhythm at baseline to Warfarin and Aspirin. We propose the ABC-HF as a strategy of integrated care management. ABC-HF stands on three pillars: i) Adherence to Guideline-Directed-Medical-Therapy, defined as ACE inhibitors/ARBs plus Beta-Blockers plus MRAs; ii) Better symptom control, defined as NYHA category I-II; iii) Comorbidities optimisation, as per guideline-directed management of hypertension, previous myocardial infarction, previous stroke, peripheral vascular disease, (incident) atrial fibrillation, etc. Patients were managed adherent to the ABC-HF strategy if all the three conditions were fulfilled. Main outcome was the composite of ischemic stroke, intracranial hemorrhage, all-cause death.

Results

A total of 2,264 patients were available for analysis (mean [SD] age 60.8 [11.4] years, 450 [19.9%] females). Overall, 254 (11.2%) patients were managed adherent to ABC-HF: 199 (8.8%) adherent to no criteria; 905 (40.0%) to one criterion; and 906 (40.0%) to two criteria. Over a mean (SD) follow-up of 3.55 (1.78) years there were 602 (26.6%) events. Patients managed adherent to ABC-HF reported a lower rate of composite outcome compared to those non-adherent (16.1% vs. 27.9%, p<0.001). A Cox multivariate regression analysis adjusted for age, sex, ejection fraction, randomized treatment, and Minnesota physical domain score showed that clinical management adherent to ABC-HF was associated with a reduction in the risk of the primary composite outcome (HR 0.54, 95% CI 0.38-0.76). A progressively higher number of ABC-HF criteria fulfilled was associated with a progressively lower risk [Figure 1].

Conclusion

In a cohort of HFrEF with severe ventricular dysfunction, adherence to ABC-HF, as an integrated care management for HF patients, is associated with a lower risk of adverse outcomes. Higher numbers of ABC-HF criteria fulfilled is associated with a progressively lower risk.ABC-HF Criteria and Risk of Composite Ou
Validation of the ATTR-CM score for transthyretin amyloid cardiomiopathy in a mediterranean cohort of patients at risk
Authors: Cediel G , Santesmases J , Domingo M , Moragas G , Sola M , Garcia-Calvo X , Guix G , Pacho C , Santiago-Vacas E , Borrellas A , Codina P , Figuerola N , Ruiz-Cueto M , Lupon J , Bayes-Genis A
Published: November 2023

Background

Transthyretin Amyloid Cardiomiopathy (ATTR-CM) is an emerging underdiagnosed cause of heart failure. 99mTc-3, 3-diphosphono-1,2-propanodicarboxylic acid (DPD) allows ATTR-CM diagnosis in the absence of histology. Recently a simple clinical score to identify increased risk of ATTR-CM in patients with heart failure and preserved left ventricular ejection fraction has been developed and validated.

Purpose

To assess the prevalence of ATTR-CM in a Mediterranean cohort of patients at risk, and to externally validate the ATTR-CM score. We also explore its diagnostic accuracy improvement by adding N-terminal pro-B-type natriuretic peptide (NTproBNP).

Methods

Retrospective cohort study of consecutive patients with suspected cardiac amyloidosis referred to DPD planar test between March 2017 and November 2020. Scans were reported using a visual grading system (0 to 3 increasingly; 2-3 positive) on planar images (anterior, left oblique anterior and lateral). Patients with clonal dyscrasia or those without rule-out tests (serum free light chain assay, and serum and urine protein electrophoresis with immunofixation) were excluded. Discrimination was obtained using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve based on the ATTR-CM score [High risk: score ≥ 6. Components and punctuation: age (60-69 = 2 points; 70-79 = 3 points; ≥80 = 4 points), male sex = 2 points, hypertension diagnosis = -1 point, ejection fraction <60% = 1 point, posterior wall thickness ≥12 mm = 1 point, relative wall thickness (septal + posterior wall thickness/left ventricular end diastolic diameter) >0.57 = 2 points]. Calibration was assessed with the Hosmer-Lemeshow goodness- of-fit test.

Results

A total of 200 patients were included with a mean age of 78.5 ± 11 years, 45.5% male, left ventricular ejection fraction 58%±12 and a median NTproBNP of 2310 pg/ml (Figure 1). 81 (40.5%) patients were categorized as a high-risk group due to score value ≥6. Prevalence of ATTR-CM was 36%. The AUC for ATTR-CM score in our cohort was 0.82 (95% CI 0.75-0.89) with an appropriated calibration (Figure 2). The addition of NTproBNP to the score did not increase the AUC (P = 0.18), with a Net Reclassification Improvement (NRI) of 0.013 (95% CI - 0.102 to 0.210).

Conclusion

A simple clinical score is a valid and reliable tool for ATTR-CM diagnosis in our Mediterranean cohort. Added to clinical suspicion, it can improve the diagnostic workup for ATTR-CM, irrespective of NTproBNP values.Demographic and clinical characteristicsAUC of ATTR-CM score in our cohort
The prognostic role of clinical features and biomarkers in patients hospitalized with cardiorenal syndromes
Authors: Theofilis P , Vordoni A , Volis N , Doumani-Korka G , Kampourelli A , Xanthopoulou E , Kalaitzidis R G
Published: November 2023

Background

Cardiorenal syndromes (CRS), involving the heart-kidney cross-talk and the activation of neurohumoral and inflammatory pathways, is an entity characterized by high morbidity and mortality.

Objective

To evaluate the prognostic role of risk factors and biomarkers in patients hospitalized for CRS.

Methods

In this prospective, observational cohort study, 113 consecutive patients hospitalized for CRS were enrolled. Socio-demographic characteristics, personal medical history, and prior medication use were recorded upon admission, and echocardiography was performed. Moreover, an array of blood markers were measured. The endpoint of interest was a composite of death or dialysis dependence at discharge.

Results

Patients were classified into two groups; Group 1 (N = 59): discharged being dialysis-independent, Group 2 (N = 54): death/dialysis dependence at discharge. No major differences were detected in baseline characteristics between the two groups. Group 2 patients used renin-angiotensin-aldosterone system blockers (RAASb) less often (Group 1: 69.5% vs. Group 2: 46.3%, p = 0.01) and more frequently presented with oliguria/anuria (Group 1: 28.8% vs. Group 2: 70.4%, p<0.001) and any infection (Group 1: 33.9% vs. Group 2: 55.6%, p = 0.02). No dissimilarities were noted in echocardiographic markers. Group 2 patients had significantly lower hemoglobin, serum albumin, bicarbonate, and 25-hydroxy-vitamin D (25OHD) (Figure 1). At the same time, N-terminal prohormone brain natriuretic peptide, serum potassium, and parathyroid hormone (PTH) were significantly higher in Group 2 patients (Figure 1). In a multivariate regression analysis, lack of RAASb was independently associated with a 17.7-fold increased risk of death or dialysis dependence at discharge, while the decreasing 25OHD/PTH ratio (β coefficient -0.01, p = 0.007) and increasing admission serum potassium levels (β coefficient 0.82, p = 0.03) increased the possibility of facing the composite endpoint. Following a receiver operating characteristic curve analysis, 25OHD/PTH ratio emerge as the most accurate predictor of facing the composite endpoint, with an ideal cutoff of 103.7 (sensitivity 81%, specificity 74%) (Figure 2).

Conclusion

Lack of prior RAASb use, high admission serum potassium, and a low 25OHD/PTH ratio are associated with poor prognosis in patients hospitalized for CRS.Figure 1Figure 2
Association between triglyceride with all-cause mortality and cardiovascular outcomes in heart failure patients
Authors: Ren Q W , Chan H C , Tsang T W , Tse Y K , Wu M Z , Xu X , Yiu K H
Published: November 2023

Background

Remnant cholesterol, identified by triglyceride-rich lipoprotein, is increasingly acknowledged as a significant causal risk factor for ischemic heart diseases. The association with cause-specific outcomes in heart failure (HF) settings remains unexplored. This study aims to determine the association between triglyceride levels with all-cause mortality and cardiovascular outcomes in patients with HF.

Methods

Using a previously validated territory-wide clinical information registry, all eligible patients with HF (N = 127124) from 1996 to 2020 were enrolled. Triglyceride levels associated with risk of mortality were evaluated on a continuous scale using restricted cubic spline curves and by categories of triglyceride using Cox proportional hazards regression model with competing risks as appropriate. The primary outcomes were all-cause mortality and cardiovascular death (CVD). Secondary outcomes included ASCVD (a composite of myocardial infarction, unstable angina, arterial revascularization or ischemic stroke) and HF readmission or death.

Results

The mean age of the study population was 71.4±12.2 years and 65869 (51.8%) were male. Notably, when we investigated the association of triglyceride levels with admission or death for ASCVD, a positive relationship was seen in high triglyceride levels and ASCVD admission or death while neutral in low triglyceride levels. Conversely, when we investigated the association with readmission or death for HF, an inverse relationship was found where lower triglyceride levels were associated with higher risks of HF readmission. Together, the association between triglyceride levels and the risk of all-cause mortality and CVD was an U-shaped curve. The risk of all-cause mortality reached a nadir between triglyceride levels of 1.12 mmol/L and 3.28 mmol/L and was lowest at 1.95 mmol/L.

Conclusion

In the HF population, low and high levels of triglyceride were associated with increased risks of all-cause mortality and CVD compared with those with midrange levels. Triglyceride was positively associated with ASCVD while inversely associated with HF admission or death. The lowest risk of all-cause mortality was found at a triglyceride concentration of 1.95 mmol/L.TG and mortalityTG and CVD
Effects of empaglifozin on collagen biomarkers in patients with heart failure. Results from the EMPEROR trials
Authors: Ferreira J , Sumin M , Butler J , Zannad F
Published: November 2023

Background

Extracellular matrix remodeling is one of the key pathways in progression of Heart Failure (HF). Clinical trials demonstrated that SGLT-2 inhibitors improved cardiovascular outcomes in HF patients, which may be partly explained by an effect on cardiac remodeling. Supporting data from preclinical studies suggested effects of SGLT-2 inhibitors on collagen synthesis and attenuation of fibrosis. However, the effect of SGLT-2 inhibitors on collagen turnover in HF patients is not fully elucidated.

Purpose

In patients of the EMPEROR-Preserved and EMPEROR-Reduced trials, across a wide spectrum of ejection fraction and renal function, the effect of empagliflozin on serum markers of collagen turnover was investigated.

Methods

1084 patients (545 in empagliflozin and 539 in placebo) were included in the analysis. Biomarkers measured from serum samples at baseline, 12 and 52 weeks included PICP (a collagen type I formation marker; ELISA), PRO-C3 (a collagen type III formation marker; ECLIA), PINP (a collagen type I formation marker; ECLIA, Roche Diagnostics), PRO-C6 (a collagen type VI formation marker; ECLIA), C1M and C3M (markers of collagen type I and III degradation CLIA). A mixed model repeated measurements model (MMRM) was used to evaluate the treatment effects on the analysed biomarkers.

Results

Treatment with empagliflozin vs. placebo reduced PICP levels at week 12 and week 52, and reduced PRO-C3 at week 52. In contrast, no significant effect was observed on PINP, PRO-C6, C1M or C3M levels (Table 1).

Conclusion

Among patients with chronic HF, across a wide range of EF and of renal function, treatment with empagliflozin reduced the serum levels of PICP, a collagen type I formation marker, both at weeks 12 and 52 and PRO-C3, a collagen type III formation marker, at week 52. These results add support for an anti-fibrotic effect of empagliflozin and may help to explain the clinical effect of SGLT-2 inhibitors on cardiac remodeling.
Redox state of human serum albumin predicts 1-year prognosis in patients with heart failure: a single center prospective cohort study
Authors: Nishikawa T , Ueyama J , Miyata S , Shimizu S , Shibata Y , Yamada S
Published: November 2023

Background

As chronic inflammation would be a fundamental underlying mechanism in the pathogenesis in patients with heart failure (HF), oxidative stress has a possibility to closely associate with the prognosis. However, little is known about the association of oxidative stress with the prognosis in HF patients.

Purpose

In this study, we assessed the association of the fraction of human mercapto-albumin [f(HMA)], an index of the redox state of human serum albumin, with prognosis in patients hospitalized for HF with the aim to find the possible biomarker available on the prediction for adverse events in HF patients.

Methods

A single-center prospective cohort study was conducted. In the cohort, 290 ambulate patients admitted for acute HF or exacerbation of chronic HF were registered. Of these, 182 who were successfully followed-up patients were analyzed (median age: 79 years, men: 68.3%. median follow-up: 365 days). The primary outcome was a composite of HF rehospitalization and all-cause mortality. The high-performance liquid chromatography postcolumn bromocresol green method was used to part human serum albumin into human nonmercaptalbumin (oxidized form) and human mercaptalbumin (HMA, reduced form). We divided patients into two groups by median f(HMA) level. Kaplan-Meier Curve and the Cox proportional hazards model was used to examine the significance of f(HMA) as a prognostic indicator of HF patients, adjusting for potential confounding factors.

Results

Median level of f(HMA) was 57.2%. During 50,965 person-days of follow-up, 52 patients (28.6%) were re-hospitalized due to HF exacerbation, and 25 patients (13.7%) died due to cardiac or noncardiac reasons. Log-rank analysis showed that a high f(HMA) group reduced adverse events (Fig. 1). In the Cox proportional hazards model, a high level of f(HMA) was associated with a reduced risk of composite outcomes (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.39-1.07). In the subgroup analysis, high f(HMA) showed an event-reducing effect in HF rehospitalizations (HR 0.53; 95% CI 0.30-0.94), but not in all-cause mortality (HR 0.61; 95%CI 0.27-1.38).

Conclusion

The findings of this study support that f(HMA) could be a novel prognostic biomarker for HF patients.Fig. 1
Contribution of the left atrial speckle tracking in the evaluation of left ventricule filling pressure in acute coronary syndromes
Authors: Brahim A S M A , Mghaieth Zghal F A T H I A
Published: November 2023

Introduction

A non invasive estimation of diastolic function with echocardiography according to consensual methods, ie American society of Echocardiography (ASE) / European association of cardiovascular imaging (EACVI) algorithm 2018, is considered an integral essential part of the clinical evaluation of patients presenting with symptoms of acute coronary syndrome (ACS). Left atrial (LA) longitudinal strain in the frame of speckle tracking echocardiography (STE) was reported recently to have additive diagnostic value to assess left ventricle (LV) filling pressures (LVFP) in a large spectrum of cardiovascular diseases.

Our study aim is to assess the accuracy of LA strain in evaluating LVFP in patients with ACS, as a single parameter.

Methods

Our study was monocentric in our cardiology department led prospectively between April 20, 2022, and June 30, 2022. We included all patients admitted to our department for evolving ST elevation (STEMI) or non-ST elevation (NSTEMI) myocardial infarction (<48 hours from onset of symptoms). Echocardiographic measurements were performed according to ASE/EACVI in less than 24 hours. They were divided into two groups according to the elevation of LVFP group 1 with non-elevated LVFP vs group with elevated LVF. LA-GS was assessed using images obtained in apical 4- and 2-chamber views , with attention to optimal visualization of the LA. The endocardial border of the LA was traced manually. Left atrial reservoir strain (LARS) was calculated from LV-end diastole, and pump strain (LAPS) after the onset of the p-wave in the electrocardiogram.

Results

Fifty patients were included in our study. The mean age was 59 ± 12 years. 72%(36) of our population was men. 34%(17) of the population had elevated LVFP (Group2) with a male predominance of 82% (14). They were active smokers in 64% (11), 52%(9) had hypertension, 70% (12) had diabetes mellitus, 47%(8) had dyslipidemia and 35% (6) were hospitalized for NSTEMI.

The mean LARS and LAPS were 26.9%, and 15.2% in group 1 vs 15.1%, and 7.1% respectively in group 2 with a difference statically significative p = 0.001, and p = 0.002 respectively.

The area under the curve was 0.910 (LARS) and 0.850 (LAPS).

The best cut-off for the LAPS was 11.5% with 100% of sensibility and 63% of specificity, for the LARS the best cut-off was 18% with 95% of sensibility and 66% of specificity.

Conclusion

LA-GS includes a reproducible and simple method for LVFP assessment in ACS. it provides an additional variable that can contribute when one of the other parameters is missing.
Left ventricular longitudinal myocardial function in heart failure patients with transition to preserved ejection fraction from reduced ejection fraction and those with preserved ejection fraction
Authors: Nagai S , Nishimori M , Todo S , Oota E , Odajima S , Takeuchi K , Ichikawa Y , Kintsu M , Yamauchi Y , Shiraki H , Yamashita K , Fukuda T , Hisamatsu E , Hirata K , Tanaka H
Published: November 2023

Background

Left ventricular (LV) longitudinal myocardial dysfunction is considered the first marker of a preclinical form of heart failure (HF) with preserved ejection fraction (HFpEF), and is strongly associated with poor outcomes. LV ejection fraction (LVEF) may improve over time during treatment or follow-up in some patients with HF with reduced ejection fraction (HFrEF). Furthermore, it has been reported that patients with HF with improved EF, known as HFimpEF, which was defined as current LVEF > 40% but any previously documented LVEF ≤ 40%, had favorable outcomes compared to those with HFpEF. However, LV longitudinal myocardial function in patients with previously reduced LVEF who had improved LVEF to normal range (≥ 50%), and its association with cardiovascular events remains unclear.

Purpose

The purpose of this study was the comparison of LV longitudinal myocardial function in patients with HFpEF and those with previously reduced LVEF who had improved LVEF to normal range (reduced LVEF-HFpEF), and to investigate whether LV longitudinal myocardial function was associated with cardiovascular events.

Methods

We retrospectively studied 70 patients with HFpEF and 45 patients with reduced LVEF-HFpEF. Reduced LVEF-HFpEF was defined as current LVEF ≥ 50% but any previously documented reduced LVEF < 50% (mean: 34 ± 10%). HFpEF was defined as current and all previous LVEF reports ≥ 50%, and met the HFA-PEFF diagnostic algorithm criteria. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS) by means of two-dimensional speckle-tracking strain. The primary endpoint was defined as cardiovascular death over a median follow-up period of 5.0 (0.5-9.0) years.

Results

As expected, the Kaplan-Meier curve indicated that patients with reduced LVEF-HFpEF experienced fewer cardiovascular death than those with HFpEF (Figure A). GLS in patients with HFpEF was significantly lower than that in patients with reduced LVEF-HFpEF (13.6 ± 3.5% vs. 14.8 ± 2.2%, P = 0.03) regardless of similar LVEF (55.7 ± 3.3% vs 56.8 ± 5.0%, P = 0.15). An important finding of the multivariate Cox proportional hazards analysis showed that GLS was an independently associated with cardiovascular death (Figure B).

Conclusion

Impaired LV longitudinal myocardial function was observed in patients with HFpEF compared to those with reduced LVEF-HFpEF regardless of similar LVEF. Moreover, LV longitudinal myocardial function was independently associated with cardiovascular death HF patients with current LVEF ≥ 50%. Our findings may provide new insights for the management of HF patients.FigureAFigureB