bluuebunny/crossref_metadata_2025 huggingface dataset:
Epicardial adipose tissue is associated with an increased risk of mortality and hospitalizations in patients with heart failure with preserved ejection fraction
Authors: Grubler M , Binder C , Duca F , Kronberger C , Polednicek M , Rettl R , Hartmann A , Beitzke D , Loewe C , Dona C , Badr-Eslam R , Hengstenberg C , Kastner J , Bergler-Klein J , Kammerlander A A
Published: November 2023

Background

Accumulating evidence suggests that epicardial adipose tissue (EAT) plays a critical role in heart failure (HF). Previous studies raised the possibility of an association with mortality and hospitalizations, but data in preserved ejection fraction (HFpEF) is sparse.

Purpose

To investigate the association of epicardial fat measured by cardiac magnetic resonance imaging (CMR) with the combined end point of heart failure hospitalizations and cardiovascular death in patients with heart failure with preserved ejection fraction

Methods

In this secondary analysis of a prospective cohort study recruiting participants with HFpEF between July 2012 and March 2018 at a tertiary care centre. Patients with cardiac amyloidosis were excluded. The combined primary endpoint of this analysis consists of heart failure hospitalizations and cardiovascular mortality. The statistical analysis plan consisted of a Cox proportional hazard regression adjusted for multiple potential confounders. Adjustments were predefined and selected by their clinical relevance. EAT volume was measured using a modified Simpson rule, EAT area was measured in the four-chamber view. EAT was defined from visceral (immediately adhering the myocardium) to the parietal layer of the pericardium. Epi-pericardial tissue was excluded. We used dark blood steady-state free precision (SSFP) at end-diastole. If unavailable we used bright blood SSFP or true fast imaging with steady-state free precession.

Results

We studied 206 patients (69% women, mean age 71±9 years, median N-terminal prohormone of brain natriuretic peptide [NT-proBNP]: 1090 IQR 420 – 1997pg/mL). During mean follow-up of 78±35 months, 78 patients (37%) died of a cardiovascular cause. In multivariate analysis adjusting for age, gender, atrial fibrillation, left-ventricular ejection fraction (EF), right ventricular (RV) end-diastolic volume index, RVEF and NT-proBNP, EAT was significantly associated with a higher risk of the composite outcome (HR 1.07 [95% CI 1.02-1.12], P = 0.007). Additional adjustments for hepatic-, renal- and pulmonary function as well as metabolic biomarkers did not materially change the results. There was no statistically significant association with pulmonary pressures on right heart catheterization.

Conclusions

EAT accumulation is associated with increased risk for mortality and hospitalizations in patients with HF with preserved ejection fraction. This finding supports the rational for future interventional studies of EAT in HFpEF.

Conclusions

EAT accumulation is associated with increased risk for mortality and hospitalizations in patients with HF with preserved ejection fraction. This finding supports the rational for future interventional studies of EAT in HFpEF.
By using the new hemodynamic definition of pulmonary hypertension in patients with left heart disease the prognostic value of different phenotypes might be lost
Authors: Bech-Hanssen O , Astengo M , Karason K , Bollano E
Published: November 2023

Background and aims

In the 2022 ECS/ERS pulmonary hypertension (PH) guidelines the threshold for increased pulmonary vascular resistance (PVR) was lowered from 3 to 2 Wood Units (WU). Consequently, in patients with PH due to left heart disease, the proportions of patients with combined pre- and postcapillary PH (CpcPH) will increase while the proportion with isolated post-capillary PH (IpcPH) will decrease. In the present study we investigate in patients with left heart disease the impact of this revision in terms of hemodynamic profile, right ventricular (RV) function and prognostication. Methods. Two-hundred and two patients consecutively referred for heart transplant or heart failure work-up were included with right heart catheterization and echocardiography within 48 hours. RV dysfunction was graded using a novel echocardiographic score allocating one point each for (1) systolic pulmonary artery pressure (PAP) >40 mmHg, (2) reduced tricuspid annular plane systolic excursion (TAPSE<17 mm), (3) RV area dilatation, (4) moderate/severe tricuspid regurgitation and (5) reduced inferior cava collapsibility. For assessment of prognostication, we studied the end-point of all-cause mortality. Results. One-hundred and seventy-three patients (86%) had left ventricular ejection fraction <40%. Eighty-nine patients (44%) underwent heart transplantation and the median (25%; 75% percentile) follow-up time (years) was 1.8 (0.35; 6.7). Sixty patients (30%) had mean PAP<20 mmHg, thus no PH. Ninety-six patients (48%) had IpcPH using PVR 3 WU as threshold. Lowering the threshold to PVR 2 WU decreased the corresponding proportion to 24%. The degree of backward failure (PA wedge pressure), forward failure (cardiac index) or RV dysfunction (RVD score) did not significantly differ by the change in hemodynamic definition (Table). With the previous hemodynamic definition, the Kaplan-Meier curves demonstrated increased mortality in CpcPH patients compared with IpcPH (Figure B). Using the new definition this difference was not present (Figure B). Conclusions. The revised hemodynamic definition of PH significantly increases the proportion with CpcPH, but does not significantly alter the hemodynamic or RV function profiles in left heart disease patients with IpcPH or CpcPH phenotype. However, our findings indicate that by using the new hemodynamic definition of IpcPH and CpcPH phenotype the prognostic value of this hemodynamic classification might be lost.Table
Sleep-disordered breathing is associated with fibrosis and impaired diastolic function
Authors: Wester M , Hegner P H , Tafelmeier M T , Lebek S L , Provaznik Z P , Floerchinger B F , Schmid C S , Maier L S M , Arzt M A , Wagner S W
Published: November 2023

Background

Emerging evidence is linking sleep-disordered breathing (SDB) to diastolic dysfunction. SDB-induced hypoxia may stimulate the development of cardiac fibrosis which then causes diastolic dysfunction. We investigated the association between SDB and myocardial collagen and PDGF mRNA levels and how collagen mRNA levels are linked to parameters of diastolic dysfunction.

Methods

RA biopsies were collected from 31 patients undergoing elective coronary artery bypass grafting in the prospective observational study CONSIDER-AF. Tissue mRNA levels of collagen type I (Col1A), PDGFα, and PDGFβ were quantified using real-time qPCR on ViiA 7 real-time PCR system. NT-pro-BNP levels were measured in the serum via ELISA blots. The apnea-hypopnea-index (AHI) was registered in portable SDB-monitoring. Echocardiography was performed to assess diastolic function.

Results

First, we investigated an association of SDB and cardiac fibrosis. AHI was correlated with tissue mRNA levels of Col3a (p = 0.0239, Fig A), PDGFα (p = 0.0414, Fig B), and PDGFβ (p = 0.0024, Fig C). Then, we investigated an association between cardiac fibrosis and diastolic dysfunction. Tissue mRNA levels of Col3A were inversely correlated with lateral (p = 0.0196, Fig D) and septal E’ (p = 0.0006, Fig E) as a marker for diastolic relaxation. Higher ratios of E/E’mean were correlated with increased tissue mRNA levels of Col3A (p = 0.0368, Fig F). NT-pro-BNP which is a diagnostic criterion for heart failure with preserved ejection fraction was correlated with Col3 levels (p = 0.0247, Fig G).

Discussion: Our findings indicate that SDB is linked to fibrosis which is associated with diastolic dysfunction.
Heart failure with improved ejection fraction: patients' characters and predictors for improvement
Authors: Segev A , Avrahamy B , Fardman A , Regev O , Younis A , Grupper A
Published: November 2023

Introduction

Heart failure with improved ejection fraction (HFimpEF) is a relatively new definition, which presents a diagnostic and therapeutic challenge. Little is known about these patients' characteristics and predictors for EF improvement.

Purpose

Characterizing the profile of HFimpEF patients and evaluate predictors for EF improvement within heart failure with reduced ejection fraction (HFrEF) patients.

Methods

The cohort included ambulatory HFrEF patients (EF≤40%) who had two consecutive echo exams at least 6 months apart in a single tertiary medical center. Patients who improved their EF from ≤40% to >40% and by ≥10% (improved group) were compared to those who did not (not-improved group). Clinical, electrocardiographic and echocardiographic data were collected and compared between the groups.

Results

A total of 567 HFrEF patients (72% male, 54.3±14.4 years old) were analyzed. Patients without EF improvement (n = 393) were more likely to be male, had more comorbidities and had higher rates of ischemic cardiomyopathy (ICMP), compared with the improved group (n = 174) (Table). Lack of improvement in EF was also associated with lower EF and higher left and right ventricular diameters in the first echo.

In a multivariate analysis model adjusted to all statistically significant variables in the univariate analysis, predictors for lack of EF improvement were male sex (adjusted odds ratio [OR] 1.63, 95% CI 1.02-2.61; P = 0.041), ICMP (OR 3.98, 95% CI 2.03-7.81; P<.001), larger left ventricular end diastolic and end systolic diameters (OR 2.07, 95% CI 1.44-2.98 and OR 1.84, 95% CI 1.36-2.5, respectively; P<.001 for both) and enlarged right ventricle (OR 1.93, 95% CI 1.11-3.36; P = 0.02), while higher EF at baseline was a positive predictor for improvement (OR 0.95, 95% CI 0.92-0.98; P = 0.001) (Figure). Interestingly, NYHA functional class was not associated with EF improvement (OR 1.16, 95% CI 0.87-1.55; P = 0.306).

Hospitalization and mortality rates were both higher in the not-improved group (median of 1 (IQR 1-2) vs. 0 (IQR 0-1); P<.001 and 24% vs. 13%; P = 0.001, respectively). Patients in both groups were generally treated with high rates of guideline directed medical therapy (GDMT) for HFrEF. Although no correlation was found between GDMT and EF improvement, these drugs were associated with reduced hospitalization and mortality rates in both groups.

Conclusions

Improvement in EF among HFrEF patients may be predicted by the HF etiology and echocardiographic parameters. HFimpEF patients have better prognosis compared to HFrEF patients. While GDMT was not associated with EF improvement, it improved outcomes in both HFimpEF and HFrEF regardless of EF.
Clinical predictors of right ventricular dysfunction and association with adverse outcomes in peripartum cardiomyopathy
Authors: Imran T F , Ataklte F , Lopez D , Mohebali D , Bello N A , Gaziano J M , Djousse L , Coglinease E , Arany Z , Sabe M , French K , Poppas A , Wu W , Choudhary G
Published: November 2023

Background

Peripartum cardiomyopathy (PPCM) is a type of pregnancy associated heart failure with reduced ejection of unknown etiology that is associated with significant morbidity and mortality in young women. It is a leading cause of peripartum maternal death in the United States, with mortality as high as 25% in some cohorts, and accounts for approximately 50% of cases of maternal cardiogenic shock.

Purpose

We sought to identify factors associated with right ventricular (RV) dysfunction and elevated RV systolic pressure (RVSP) and association with adverse outcomes in PPCM.

Methods

We conducted a multi-center cohort study to identify subjects with PPCM with the following criteria: LVEF < 40%, development of heart failure within the last month of pregnancy or 5 months of delivery and no other identifiable cause of heart failure with reduced ejection fraction. Outcomes included a composite of 1) major adverse events (need for extra-corporeal membrane oxygenation, ventricular assist device, orthotopic heart transplantation or death) or 2) recurrent heart failure hospitalization.

Results

In all, 229 women (1993 to 2017) met criteria. Mean age was 32.4 ± 6.8 years, 28% were of African descent, 50 (22%) had RV dysfunction, and 38 (17%) had RVSP > = 30mmHg. After a median follow-up of 3.4 years (IQR 1.0-8.8), 58 (25%) experienced the composite outcome of adverse events. African descent, family history of cardiomyopathy, LVEF, and RVSP were significant predictors of RV dysfunction (Table 1).

Using Cox proportional hazards models, we found that women with RV dysfunction were three times more likely to experience the adverse composite outcome: HR 3.21 (95% CI: 1.11-9.28), p = 0.03 in a multivariable model adjusting for age, race, body mass index, preeclampsia, hypertension, diabetes, kidney disease and LVEF. Women with RVSP >= 30mmHg had a lower probability of survival free from adverse events (log rank p = 0.04) (Figure 1).

Conclusion

African descent and family history of cardiomyopathy were significant predictors of RV dysfunction. RV dysfunction and elevated RVSP were significantly associated with a composite of major adverse cardiac events. This at-risk group may prompt closer monitoring, genetic testing, or early referral for advanced therapies.Table of predictorsSurvival curves
The effect of empagliflozin on ketone bodies in patients with heart failure with reduced ejection fraction (Empire HF)
Authors: Larsen J H , Jensen J , Andersen C F , Hoejlund K , Kistorp C M , Poulsen M I , Tuxen C , Gustafsson F , Koeber L , Schou M , Moeller J E , Omar M
Published: November 2023

Background

The thrifty-substrate hypothesis suggests that Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors increase plasma levels of ketone bodies and create a salutary switch in myocardial fuel metabolism.

Purpose

We investigated the effect of SGLT2 inhibitor on plasma beta-hydroxybutyrate in patients with heart failure and reduced ejection fraction (HFrEF).

Method

This is a post hoc analysis of the Empagliflozin in Heart Failure Patients with Reduced Ejection Fraction (Empire HF) trial, an investigator-initiated, double-blind, randomized, placebo-controlled trial which enrolled 190 stable HFrEF patients with a left ventricular ejection fraction (LVEF) of ≤40%. Patients were randomly assigned (1:1) to empagliflozin 10 mg once daily, or matching placebo. Analyses were performed in patients with complete data using a linear-mixed effect-model with log-transformed beta-hydroxybutyrate, adjusted for baseline beta-hydroxybutyrate value, age, sex, and type 2 diabetes.

Results

A total of 188 (99%) patients had available data. The groups were well-matched with respect to baseline characteristics. Mean age was 64 (SD, 11) years; LVEF was 29 (SD, 8) %, 13% had type 2 diabetes, New York Heart Association (NYHA) class II was found in 78%. Median plasma levels of beta-hydroxybutyrate were 0.10 (inter quartile range (IQR) 0.05–0.18) mmol/l at baseline, and 0.11(IQR 0.07–0.2) mmol/l at follow-up in the empagliflozin group. In the placebo group, baseline and at follow-up concentrations were 0.10 (0.06–0.17) mmol/l and 0.09 (0.05–0.15) mmol/l, respectively. Empagliflozin increased plasma levels of beta-hydroxybutyrate compared to placebo (adjusted between-groups treatment effect; Ratio of change 1.45 [95%confidence interval (CI); 1.12–1.87], p = 0.005 (Figure 1). The effect of empagliflozin on beta-hydroxybutyrate outcomes was consistent across multiple subgroups analyses including baseline median age, sex, N-terminal-pro B-type natriuretic peptide (NT-proBNP) cut-off 600 pg/mL, treatment with sacubitril–valsartan or beta-blockers, measured glomerular filtration rate (GFR) level, hemoglobin A1c (HbA1c) level, and concomitant type 2 diabetes (all P interaction>0.05).

Conclusion

In patients with HFrEF, predominantly without diabetes, short-term treatment with empagliflozin increased the levels of beta-hydroxybutyrate. The absolute changes were modest and the exact contribution of ketone bodies to the cardiovascular benefits of SGLT2 inhibitors requires further clarification.Figure 1Table 1
Accelerometer-measured physical activity in patients with heart failure and reduced ejection fraction: determinants and relationship with patient-reported health status
Authors: Larsen J H , Andersen C F , Omar M , Kistorp C M , Tuxen C D , Gustafsson F , Koeber L , Poulsen M I , Broend J C , Moeller J E , Schou M , Jensen J
Published: November 2023

Background

Accelerometer-measured physical activity is an increasingly used endpoint in heart failure (HF) trials.

Purpose

We aimed to investigate the determinants of accelerometer-measured physical activity and to establish the minimal clinically important difference (MCID).

Methods

Post-hoc analysis of the Empire HF trial, including stable outpatients with HF with reduced ejection fraction (HFrEF). Physical activity was quantified as average accelerometer counts per minute (CPM) with higher values representing higher activity. Associations between activity level and important clinical variables [age, sex, body mass index, N-terminal pro-brain natriuretic peptide, left ventricular ejection fraction (LVEF), atrial fibrillation, and anemia], as well as patient-reported health status (Kansas City Cardiomyopathy Questionnaire, KCCQ) were assessed.

Results

Complete data were available in 180 (95%) patients (86% male, mean age 65 years, mean LVEF 30%). Baseline median physical activity level was 1318 CPM (Q1-Q3 1111–1585). At baseline, age and anemia were independently associated with activity level (β-coefficients: -10 CPM per year age increase [95% CI -16 to -5.1], p = 0.00015, and -126 CPM for presence of anemia [95% CI -9.1 to -244], p = 0.035). Moreover, a significant independent association was observed between activity level and all KCCQ summary scores (β-coefficient point estimates of 3.7, 4.6, and 4.9 CPM, all p<0.02). For 12-week changes, only the KCCQ-clinical summary score (CSS) was associated with activity level, with a mean increase of 17.5 CPM [95% CI 1.5 to 34.0], p = 0.032, for every clinically relevant 5-point increase in KCCQ-CSS, corresponding to the MCID.

Conclusion

In patients with HFrEF, high age and anemia were independently associated with lower accelerometer-measured physical activity. Moreover, clinically relevant 5-point increases in Kansas City Cardiomyopathy Questionnaire clinical summary scores at 12 weeks were associated with an increase of 17.5 activity counts per minute, thus representing the minimal clinically important difference.Table 1.Baseline characteristicsFigure 1
Role of beta-3 adrenergic receptor polymorphism TRY64ARG in heart failure
Authors: Jimenez Rodriguez G , Elizalde-Silva J L , Manzur-Sandoval D , Cota-Apodaca L , Ramos-Enriquez A , Bucio-Reta E , Lazcano-Diaz E , Baeza-Herrera L , Santos-Martinez L , Gonzalez-Ruiz F , Gaytan-Garcia C , Hernandez-Gonzalez G L , Rojas-Velasco G
Published: November 2023

Introduction

The TRY64ARG polymorphism of the beta-3 adrenergic receptor has been associated with the onset and maintenance of hypertension, diabetes and obesity, its role in heart failure has not been studied.

Objectives

To examine the role of the TRY64ARG beta-3 adrenergic receptor in the improvement of left ventricular ejection fraction (LVEF) in patients with Heart Failure due to ischemic heart disease.

Methods

This study is a retrospective analysis based on a 5-year follow-up of patients with heart failure with decreased LVEF due to ischemic heart disease.

Results

We studied a sample of 338 patients with decreased LVEF collected from our Genetic database during the period of time from January 2012 to December 2016. In the scrutiny 26 patients did not have complete data for analysis, resulting in a final sample of 312 patients with a minimum follow-up of 5 years. The mean age was 58.9 years (SD 14), 72% of the population were men (n = 244), the frequency of hypertension was 168 (53.85%), diabetes 119 (38.14%), obesity (18.27%). The definition of LVEF improvement was defined as an incremental in more than 15%. There was no statistical difference in the medical treatment and revascularization methods. Patients with the TRY64ARG β3 adrenergic polymorphism present less improvement in the LVEF (42% vs 58%, p< 0.001).

Conclusions

The expression of the TRY64ARG polymorphism of the beta-3 adrenergic receptor in patients with HF and low LVEF is related to a lack of incremental LVEF at 5 years.
Efficacy and safety of intravenous iron repletion in patients with heart failure: a systematic review and meta-analysis
Authors: Vukadinovic D , Abdin A , Boehm M
Published: November 2023

Introduction

AFFIRM-AHF and IRONMAN demonstrated lower rates of the combined endpoint recurrent heart failure (HF) hospitalizations and cardiovascular death (CVD) by using intravenous (IV) ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), respectively in patients with HF and iron deficiency (ID) utilizing prespecified COVID-19 analyses.

Material and methods

We meta-analyzed efficacy, between trial heterogeneity and data robustness for the primary endpoint and CVD in AFFIRM-AHF and IRONMAN. As sensitivity analysis, we analyzed data from all eligible exploratory trials investigating FCM/FDI in HF.

Results

FCM/FDI reduced the primary endpoint (RR = 0.81, 95% CI 0.69-0.95, p = 0.01, I2 = 0%), with the number needed to treat (NNT) being 7. Power was 73% and findings were robust with fragility index (FI) of 94 and fragility quotient (FQ) of 0.041. Effects of FCM/FDI were neutral concerning CVD (OR = 0.88, 95% CI 0.71-1.09, p = 0.24, I2 = 0%). Power was 21% while findings were fragile with reverse FI of 14 and reversed FQ of 0.006. The sensitivity analysis from all eligible trials (n = 3,258) confirmed positive effects of FCM/FDI on the primary endpoint (RR = 0.77, 95% CI 0.66-0.90, p = 0.0008, I2 = 0%), with NNT being 6. Power was 91% while findings were robust (FI of 147 and FQ of 0.045). Effect on CVD was neutral (RR = 0.87, 95% CI 0.71-1.07, p = 0.18, I2 = 0%). Power was 10% while findings were fragile (reverse FI of 7 and reverse FQ of 0.002). Rate of infections (OR = 0.85, 95% CI 0.71-1.02, p = 0.09, I2 = 0%), vascular disorder (OR = 0.84, 95% CI 0.57-1.25, p = 0.34, I2 = 0%) and general or injection-site related disorders (OR = 1.39, 95% CI 0.88-1.29, p = 0.16, I2 = 30%) were comparable between groups. There was no relevant heterogeneity (I2>50%) between the trials for any of the analyzed outcomes.

Conclusions

Use of FCM/FDI is safe and reduces the composite of recurrent HF hospitalizations and CVD without benefit on CVD. Findings concerning composite outcomes exhibit a high level of robustness without heterogeneity between trials with FCM and FDI.Summary
Anemia and 1-year outcomes in hospitalized patients with heart failure with preserved ejection fraction: Findings from the China Cardiovascular Association Database-Heart Failure Center Registry
Authors: Qiu W , Cai A , Xia S , Yang J , Feng Y , Li L
Published: November 2023

Background

Little evidence exists regarding the association of anemia and clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF).

Purpose

To determine the associations of anemia and clinical outcomes in HFpEF.

Methods

Data were from 575 China Cardiovascular Association Database-HF Center certified secondary and tertiary hospitals across overall 31 provinces of mainland China. Between January 2017 and December 2021, 48,992 HFpEF patients with an left ejection fraction (LVEF) ≥50% and hemoglobin (Hb) data were included. According to the World Health Organization criterion (Hb <12g/dL for women and <13 g/dL for men), participants were categorized into two groups (with and without anemia). The primary outcome was a composite of hospitalization for HF and cardiovascular (CV) death, and the secondary outcomes were all-cause hospitalization and all-cause death.

Results

Among the overall patients, 50.0% were men, the mean age was 72.2 years, and 48.1% (n = 23,570) had anemia. Compared with individuals without anemia, participants with anemia were older and more symptomatic, more likely to have New York Heart Association class III/IV, and had greater comorbid burden. At 1-year’s follow-up, anemia was independently associated with an increased risk of primary outcome (hazard ratio [HR]: 1.08, 95% CI: 1.03-1.12), all-cause death (HR: 1.30, 9%% CI: 1.21-1.38), and all-cause hospitalization (HR: 1.06, 95% CI: 1.02-1.10). There was a trend toward increased risk of primary and secondary outcome with increasing severity of anemia (all P-trends were <0.05). The results were consistent in all the subgroups analyses (sex, age (≥75 and <75 years old), NYHA class (Ⅰ/Ⅱ and Ⅲ/Ⅳ), eGFR (≥60 and <60 ml/min/1.73m2)). The restricted cubic spline showed significant nonlinear relationships between primary outcome and hemoglobin as continuous variable, with a risk nadir around 13-15g/dL.

Conclusion

Anemia was common in Chinese HFpEF patients and was an independent risk factor for adverse clinical outcomes at 1 year’s follow-up. Further studies are needed to evaluate whether ameliorating anemia can improve outcome in HFpEF patients.Graphic Abstract
Impact of cardiac power output, invasively measured by right heart catheterization, on exercise capacity and clinical outcomes in patients with chronic heart failure
Authors: Shimono Y , Ishizaka S , Omote K , Nakamura K , Yasui Y , Mizuguchi Y , Takenaka S , Aoyagi H , Tamaki Y , Kobayashi Y , Tada A , Sato T , Kamiya K , Nagai T , Anzai T
Published: November 2023

Background

Cardiac power output (CPO) is a novel hemodynamics parameter that is derived from both flow and pressure, and therefore it represents the cardiac pumping ability. CPO is strongly associated with outcomes in patients with cardiogenic shock. Nevertheless, less data is available about the impact of CPO on exercise capacity or clinical outcomes in patients with chronic heart failure (CHF).

Purpose

The present study aimed to investigate the impact of CPO on exercise intolerance or morbidity and mortality in patients with CHF who underwent invasive right heart catheterization.

Methods

The study enrolled 280 consecutive patients with CHF who underwent cardiopulmonary exercise testing and right heart catheterization between 2013 and 2018. The primary outcome was composite of heart failure hospitalization and death. CPO was calculated as (mean arterial pressure × cardiac output [CO])/451. Study population was divided into 2 groups according to the established cut-off value of CPO (= 0.53 W).

Results

Patients with low CPO (n = 99) were older and lower body mass index and displayed poorer kidney function, higher plasma brain natriuretic peptide (BNP) levels and lower left ventricular ejection fraction (LVEF) as compared to patients with high CPO (n = 181). CPO was correlated with peak oxygen consumption (Peak V̇O2), peak workload achievement, and ventilatory efficiency (V̇E/V̇CO2 slope) (Figure 1), while each of CO or mean arterial pressure was not. There were 48 patients with events over a median follow-up period of 3.5 (Interquartile range 1.0-6.0) years. Patients with low CPO had a 2.0-fold higher risk of events as compared to those with high CPO (HR 1.97; 95%CI, 1.12-3.48, P = 0.02, Figure 2). In multivariable Cox regression, 0.1-decreased in CPO was associated with 19% increased adverse events even after adjustment for gender, BNP, renal function, LVEF, and pulmonary capillary wedge pressure (HR 0.81; 95%CI, 0.67-0.99, P = 0.04).

Conclusions

CPO was associated with reduced exercise capacity and poor clinical outcomes, suggesting that CPO is useful for risk stratification in patients with CHF. Further study is required to identify therapies targeting CPO to improve the exercise capacity or clinical outcomes in patients with CHF.Figure1Figure2
A prospective, observational multicenter registry of heart failure patients in Germany: preliminary results of the ongoing H2-registry
Authors: Leiner J , Koenig S , Nitsche A , Mouratis K , Seyfarth M , Baberg H , Schade A , Neuser H , Staudt A , Tebbenjohanns J , Andrie R , Niehaus M , Ferrari M W , Kuhlen R , Bollmann A
Published: November 2023

Background

Heart failure (HF) is a highly prevalent condition affecting 1-2% of the adult population in Europe. Despite pioneering improvements in HF treatment during the last two decades, hospitalization and mortality rates remain relatively high. Gathering real-world data on HF populations is crucial especially in the light of newly emerging therapeutic approaches.

Purpose

The H2-registry was set up in 2021 to provide up-to-date, real-world data on a contemporary cohort of hospitalized HF patients in Germany using a standardized set of outcome measures.

Methods

The ongoing H2-registry represents a prospective, investigator-initiated, multicenter observational registry. Inpatients ≥18 years of age with a present diagnosis of chronic or acute HF are recruited in secondary and tertiary hospitals throughout Germany. Patients are excluded if they present in any kind of shock during index hospitalization, or if they previously underwent heart transplantation or ventricular assist device therapy. Routine follow-up (FU) is conducted every 6 months. A standardized set of variables according to the International Consortium of Health Outcome Measurements (ICHOM) including a pre-defined selection of questionnaires to collect patient-reported outcome measures (PROMs) is used to objectively monitor the course of disease.

Results

Until the reference date 12/31/22, a total of 2,190 patients were included in ten active study centers. Mean age was 72 years, 36.8% were female, and mean left-ventricular ejection fraction (LVEF) was 43.4% (38.1% had an LVEF of ≤ 40%). In-hospital mortality at index case was 1.3%. Within the cohort with completed 6-month FU comprising of 976 patients, all-cause mortality was 11.3% (110). In addition, 24.2% (209) in the survival cohort had at least one HF-related re-hospitalization. Numbers for all-cause mortality and re-hospitalizations at 12-month FU were 21.3% (71) and 32.8% (86), respectively. Evaluations of Kansas City Cardiomyopathy Questionnaire (KCCQ-12) scores showed a significant improvement overall and in all sub-categories (p < 0.001) at 6- and 12-month FU.

Conclusions

The H2-registry currently represents the largest ongoing prospective registry of HF inpatients in Germany. Our preliminary data highlights the pronounced mortality risk and healthcare burden in this cohort. However, HF-related therapies initiated during the course of a hospitalization have the potential to significantly improve patients’ quality of life. In the near future, it its foreseeable that the actively recruiting H2-registry based on ICHOM-standards will markedly contribute to the collection of real-world data on HF patients.
Educational level and risk of all-cause death in patients with heart failure with reduced ejection fraction (HFrEF): a report from the WARCEF Trial
Authors: Corica B , Romiti G F , Simoni A H , Mei D A , Thompson J L P , Homma S , Proietti M , Lip G Y H
Published: November 2023

Background

The influence of social determinants of health (SDOH) on the prognosis of patients with Heart Failure and Reduced Ejection Fraction (HFrEF) is increasingly reported; however, the contribution of educational level to this risk of adverse outcomes in HFrEF is unclear.

Purpose

We aimed to explore the role of the educational level on the risk of adverse outcomes.

Methods

We used data from the WARCEF trial, which randomised HFrEF patients with sinus rhythm to receive Warfarin or Aspirin; educational level of patients enrolled was collected at baseline. We defined three levels of education: low, medium and high level, according to the highest qualification achieved or highest school grade attended, consistently to previous classification. The primary outcome for this analysis was the risk of all-cause death; we also analyzed other exploratory secondary outcomes. Outcomes were analysed using adjusted Cox-regression analysis; competing-risk analysis using Fine-Gray regression were additionally performed.

Results

2,295 patients (mean age 60.8 ±11.3; 20% females) were included in this analysis. After a median follow-up time of 3.7 [IQR: 2.0-5.0] years, 546 (23.8%) death were recorded. Highest percentage of females were in the low educational level (21.6%), while in medium education females were 19.3%, and in high educational level were 17.4%. Highest percentage of non-married people were in the low and medium educational level patients (35.7% and 41.0%, respectively), while in high education level patients, non-married were 26.4%.

Patients with low educational level had a high risk of all-cause death (adjusted Hazard Ratio [aHR] 1.44, 95% Confidence intervals (CI) 1.10-1.89) compared to those at high educational level; no statistically significant differences were observed for those with medium educational level (aHR: 1.27, 95%CI: 0.97-1.68). Survival curves for the risk of all-cause death is shown in Figure 1. Similar results were observed for the composite outcome of death, ischemic stroke or intracerebral hemorrhage. No statistically significant differences were observed for the subdistribution hazards of secondary outcomes in the competing-risk analysis.

Conclusions

Low educational status is associated with worse prognosis in HFrEF patients. These findings underline the importance of considering SDOH in the management of these subjects.Kaplan Meier Curves
Suboptimal guideline-directed medical therapy and prognosis in patients with heart failure and reduced ejection fraction: The SMYRNA Study
Authors: Kocabas U , Ergin I , Kivrak T , Yilmaz Oztekin G M , Tanik V O , Ozdemir I H , Avci Demir F , Dogdus M , Sen T , Altinsoy M , Ustundag S , Urgun O D , Sinan U Y , Uygur B , Yeni M
Published: November 2023

Background

Heart failure and reduced ejection fraction (HFrEF) is associated with an increased risk of morbidity and mortality. Despite strong evidence from the randomized-controlled trials and recommendations of guidelines, the use of guideline-directed medical therapy (GDMT) among patients with HFrEF remains suboptimal in a real-life setting.

Purpose

The Suboptimal guideline-directed Medical therapY and prognosis in patients with heaRt failure and reduced ejectioN frAction (SMYRNA) study aims to determine the prognostic significance of GDMT in patients with HFrEF.

Methods

The SMYRNA study is a prospective, multicenter, and observational study that included outpatients with HFrEF. The study population enrolled at 41 cardiology centers between January 2019 and June 2019. Patients were divided into 3 groups: those treated with ≤1 class of HF medication, 2 classes of HF medications, and 3 classes of HF medications. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure, analyzed as the time to the first event.

Results

The study population consisted of 1,062 patients with HFrEF, predominantly men (69.1%), with a median age of 68 (20–96) years. RAS inhibitors, beta-blockers, and MRAs were prescribed in 76.0%, 89.4%, and 55.1%, of the patients at the time of study enrollment, respectively. The proportions of patients receiving target doses of medications were 24.4% for RAS inhibitors, 11.0% for beta-blockers, and 11.1% for MRAs (Figure 1). The median follow-up was 24 months. The rate of primary composite outcome was 40.4% among patients treated with ≤1 class of HF medication, 32.0% among patients treated with 2 classes of HF medications, and 32.8% among patients treated with 3 classes of HF medications. Patients treated with 2 or 3 classes of HF medications had a decreased risk of cardiovascular death or hospitalization for heart failure compared to those patients receiving ≤1 class of HF medication (HR, 0.65; 95% CI, 0.49 to 0.85; P = 0.002, and HR, 0.61; 95% CI, 0.47 to 0.79; P<0.001, respectively, Figure 2).

Conclusion

The real-life SMYRNA study showed that suboptimal GDMT is strongly associated with an increased risk of cardiovascular death or hospitalization for heart failure in patients with HFrEF.Figure 1Figure 2
HFrEF phenotyping in real life
Authors: Weidenhammer A , Prausmueller S , Panagiotides N , Arfsten H , Heitzinger G , Spinka G , Barkhudaryan A , Bartko P , Huelsmann M , Pavo N
Published: November 2023

Background

In May 2021 an HFA position paper[1] by Rosano GMC et al. classified patients with heart failure with reduced ejection fraction (HFrEF) into 11 phenotypes based on blood pressure, heart rate, renal function, potassium level and rhythm and assigned them to different prescription attitudes.

Aim

We aim to investigate the distribution of phenotype frequency in our cohort and their respective outcomes.

Methods

From 2016 to 2022 we enrolled 900 advanced HFrEF patients with severely reduced ejection fraction (LVEF <35%) in a prospective registry from our tertiary care heart failure unit. Patients were grouped according to the suggested phenotypes. Distribution and outcome for the different groups was analyzed.

Results

Characteristics of the different phenotypes, the distribution and outcome are shown in Figure 1. 65.8% of patients belong to 5 categories [3, 4, 5, 7b and 9]. Baseline characteristics of these 5 profiles are shown in Table 1. With the exception of Profile 3, which is characterized by a low resting hear rate, these major profiles are all eligible to receive all 4 drugs with class I recommendation at maximal dosages (RASi, BB, MRA, SGLT2i). The 6 remaining categories, all with GDMT limiting features, comprise solely another 3.8% of patients [1.8%, 1.2%, 0.3%, 0.3%, 0.2%, 0%, for the categories 7c, 7a, 1, 2, 6, 8 respectively]. With 30.2% a significant proportion of patients could not be assigned to one profile exclusively mostly because they showed a combination of profile attributes. Thus, of all classifiable HFrEF patients, with 83.4% the majority has no GDMT limiting features and should receive full HFrEF therapy. All-cause mortality did not differ between patient phenotypes [4,5,7b and 9] and the others (p = 0.193), while uncategorizable patients had significantly worse survival (p<0.0001) (Figure 1c).

Conclusion

The study provides insight into heart failure phenotyping in a real-world setting. Most HFrEF patients are eligible for the 4 class I drugs of HFrEF medication, and only a minority may not be able to receive them. However, nearly one-third of all patients could not be categorized, including those with the poorest survival. Given these findings, the added value of the classification of patients according to this pattern seems limited in routine practice, possibly resulting from the complexity of the clinical picture of HFrEF.Figure 1  BL characteristics
Prognostic value of serum bicarbonate in patients hospitalized for acute heart failure
Authors: Martin Dorado E , Hurtado E , Martinez J , Monteiro M , Gomez I , Salvador L , Palanco C , Sanchez S , Lledo M , Martinez-Carapeto A , Cerrato P , Rama J C , Bengla B , Ocampo M , Gordillo E
Published: November 2023

Background

Acute heart failure (AHF) requiring hospitalization is associated with significant morbidity and mortality. Acid-base disorders are very common in patients with AHF due to pulmonary oedema and low tissue perfusion. However, its long-term prognostic significance remains to be clarified. We aimed to determine the relationships between serum bicarbonate (HCO3) levels, which reflect acid–base homeostasis, with long-term outcomes.

Methods

This cohort study included all patients admitted for AHF from June 2021 to August 2022 in a single center. We excluded patients who did not have available gasometric values at admission. All patients had received a primary diagnosis of acute decompensated heart failure, including signs and symptoms of fluid overload and a concentration of N-terminal pro-B-type natriuretic peptide (NT-ProBNP) of 300 pg/mL at least. Clinical and demographic characteristics of all patients were collected during hospitalization. Normal range of HCO33 were defined as 22 to 26 mmol/L. The primary objective was a composite outcome of cardiovascular death and AHF readmission.

Results

Total of 153 patients were enrolled. Median age was 75,4 ± 10,8 years and 66 (43%) patients were female. 62 (38%) patients had diabetes and 67(41%) had chronic kidney disease. The median [IQR] of NT-ProBNP at admission was 4525 (IQR 25-75: 2010-7148), 58 (38%) patients had left ventricular ejection fraction (LVEF) ≤ 40%, 90 (56%) patients had atrial fibrillation and 49 (32%) patients had coronary artery disease. Regarding acid-base disorders, 38 (24,8%) patients had high serum HCO3 level, and 53 (34,6%) patients had low serum HCO3 level. During a median follow-up period of 10 months, there were 24 deaths (15%), and 60 patients were readmitted for heart failure. High serum HCO3 level (≥26 mmol/L) was significantly associated with higher incidence of the composite outcome (24/38, 63,2% vs 48/115, 41,7%; OR 2.39, 95% CI: 1.12-5.09, p = 0,017) compared with normal and low HCO3 level. In contrast, low serum HCO3 level had lower incidence of the composite outcome (19/53, 36% vs 53/100, 53%; OR 0.5, 95% CI: 0,25-0,98, p = 0,032) compared with normal and high serum HCO3 level. Moreover, we did not find differences between groups stratified by acidaemia (OR 0.82, 95% CI: 0,32-2,08, p = 0,43), alkalaemia (OR 2,8, 95% CI: 0,69-11,26, p = 0,12) and hyperlactatemia (OR 0,72, 95% CI: 0,34-1,52, p = 0,45).

Conclusions

High serum HCO3 level, but not low serum HCO3 level, on admission was associated with composite outcome cardiovascular death or AHF readmission in patients with acute heart failure. HCO3 level seems to be a useful tool to identify acid-base disorders for stratifying the risk of adverse outcomes in patients with acute heart failure.
Point-of-care aid-to-diagnosis for heart failure using artificial intelligence based on seismocardiography acquired with a smartphone in the emergency department
Authors: Tran T L , El Ahmadie D , Mainil G , Hossein A , Meurant V , Almorad A
Published: November 2023

Background

The number of new heart failure (HF) diagnoses in hospitals constantly increases. The associated clinical signs lead to a delay in treatment. Reliable and rapid diagnostic assistance is needed at earlier stages and can be an added value to accelerate the process. Kinocardiography (KCG), based on Seismocardiography (SCG), allows the computation of non-invasive cardiac kinetic energy that is used to characterize the cardiac function and could detect HF among patients at risk.

Purpose

In a multi-centric study, test the performance of smartphone-based KCG recording in diagnosing HF in the emergency department.

Methods

Adult patients who presented with dyspnea in the emergency department (ED) were recruited. Clinical charactristics were recorded, including demographics, symptoms, medication use, and diagnostic studies. Additionally, a blood sample was collected for NT-proBNP measurement, and a 180-second KCG acquisition was acquired with a smartphone. The patient is placed supine on the back, and the smartphone is placed on his chest to acquire the precordial vibrations due to the heartbeats. From these vibrations, cardiac kinetic energy (CKE) metrics are derived, including diastolic gradient kinetic energy (ΔiKdiastolic). The final HF diagnosis was assessed from the medical record at discharge from the ED. The primary outcome is the performance of an AI based on CKE metrics at classifying HF, measured using metrics including the area under the receiver operating characteristic curve (AUROC), negative predictive value (NPV), and specificity, with two-sided 95% CIs.

Results

295 patients were recruited; among these, 106 patients were diagnosed with HF (78 [69;83] years, 26.9 [23.2;29.3] kg/m2, 42% male, 4933.0 [3299;8055] pg/ml, 67 HFpEF, 10 HFmrEF, 29 HFrEF) and 189 without HF (64 [55;74] years, 28.1 [25.5;31.4] kg/m2, 51% male, 297.0 [90;813] pg/ml). ΔiKdiastolic was significantly lower in patients with HF (0.35 [0.08;0.70] vs. 0.06 [-0.04;0.32] %, p<0.005). The AI approach resulted in an AUROC of 0.82 (0.80–0.89), sensitivity of 82.5% (72·7–90·2), and NPV of 79.3% (77·5–82·6).

Conclusion

This study shows that an AI system applied to SCG acquired during a 3-minutes examination with a smartphone can detect HF among patients presenting dyspnea. These findings highlight the potential for non-invasive, workflow-adapted, point-of-care, aid-to-diagnosis for earlier diagnosis and prognostically beneficial treatment.
Correlation and utility of the changes in sST2 level at clinician determined decompensation and recompensation
Authors: Li B , Dowley M , Langley S , Hardy-Wallace A , Cliffe P , Whiting S , Dimarco A , Zydik L , Barbagallo R , Dungu J N , Savage H O
Published: November 2023

Introduction

Soluble Suppressor of Tumorigenicity 2 (sST2) biomarker has been shown to demonstrate prognostic capabilities in patients with heart failure (HF), with serial measurements of sST2 at pre-determined time intervals providing additional predictive value for adverse outcomes. We sought to evaluate what level of sST2 level change, at clinician determined decompensation and recompensation during an acute admission for decompensated HF, could provide prognostic information for adverse outcomes.

Methods

Between January 2020 and February 2022, consecutive patients hospitalized at a secondary care hospital had sST2 measured within 24 hours of decompensated HF admission and following recompensation assessed by qualified clinicians, as part of the INST2ANT-HF study. sST2 samples were batched analysed at the end of recruitment period with a quantitative turbidimetric immunoassay. The primary outcome was the interval change between admission and discharge sST2 in patients admitted with decompensated heart failure. Related-samples Wilcoxon signed rank test was performed to evaluate for difference in sST2 at decompensation and recompensation. Comparison of median sST2 change was made using independent samples median test comparing alive and deceased patients at one year follow up.

Results

In 162 consecutive patients with paired samples, median age was 71 (IQR 61-80). 23.5% were female and 34% had an ischaemic aetiology. 94.4% presented with NYHA class III and IV and median ejection fraction was 26% (IQR 17-32). Median length of stay in hospital was 8 (IQR 5-13) days. Median levels of sST2 at decompensation and recompensation were 60.5 and 39.5ng/ml respectively (p<0.001) (Fig.1a). In patients who died within the first year, median levels of sST2, at decompensation and following recompensation, were significantly higher than in patients who were alive. (decompensation sST2 83 vs 56ng/ml; p = 0.007 and recompensation sST2 58 vs 34ng/ml; p = 0.036) (Fig. 1b). There was however no significant difference in the absolute or percentage change in sST2 level between those who died and those who survived (19.5 vs 16ng/ml, p= 0.437; 27 vs 35%, p = 0.363).

Conclusion

Our initial data demonstrates that in a cohort of patients admitted with acute decompensated HF, there was a significant difference in sST2 levels between clinician determined decompensation and recompensation. Higher levels of sST2 at both decompensation and recompensation were associated with a higher risk of mortality at one year. Utilizing newer biomarkers such as sST2 to predict outcomes may allow better risk stratification and identifying patients needing closer follow up. More research is needed however to determine what values would be useful in clinical practice.Figure 1Figure 2