Heart Failure With Reduced Left Ventricular Ejection Fraction Research Articles

ANTIHYPERTENSIVE DRUGS IN CHRONIC HEART FAILURE IN THE CZECH REPUBLIC, FOCUSING ON BETA-BLOCKERS

Objective: Hypertension is a very common comorbidity in patients with heart failure. Beta-blockers (BB) are the first choice drug together with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) in patients with heart failure with reduced left ventricular ejection fraction (HFrEF), reducing morbidity and mortality. Design and method: Data were collected in the FARmacology and NeuroHumoral Activation Registry (FAR NHL). Patients with chronic heart failure with left ventricular ejection fraction (LVEF) < 50% for at least one month were included. Results: 1,100 patients with a mean age of 65 years, 80.8% male, were included. The mean systolic blood pressure was 128.0 mm Hg, mean diastolic blood pressure was 80.0 mm Hg. Of all patients, 20% received low dose of beta-blocker (LD), 57% medium dose (MD) and 17% high dose (HD), 6.2% did not receive BB. The higher the blood pressure (LD 124/ 77; MD 129/ 80; HD 132/ 82 mm Hg; p < 0.001), LV EF (LD 29.5; MD 30.5; HD 32.0%; p = 0.003), creatinine clearance (LD 78.7; MD 87.8; HD 91.1 ml/min; p = 0.001) or weight of the patients, the higher the BB dose they received (LD 83.2; MD 88.7; HD 93.5 kg; p < 0.001). The lower the NT-proBNP, the higher the BB dose patients received (LD 767; MD 456; HD 314 pg/ml; p < 0.001). The presence of atrial fibrillation (AF) did not affect the BB dose. Patients with AF were more likely to be treated with digoxin or a combination of digoxin and BB than patients without AF (p < 0.001). Conclusions: According to FAR NHL registry, almost 94% of patients with HFrEF receive BB. A total of 17% of patients take the target dose of BB. If a patient has BB, he/she is treated with the recommended preparation in more than 99% of cases. The more severe the disease, as reflected by lower BP, creatinine clearance, LV EF, weight or higher NT-proBNP, the lower the dose of beta-blockers the patient receives and tolerates.

Predicting factors for omitting beta-blockers in patients with tachycardia-induced cardiomyopathy after successful catheter ablation for atrial fibrillation.

Tachycardia induces a reduction in the left ventricular ejection fraction (LVEF), which is defined as tachycardia-induced cardiomyopathy (TIC). Conversion to and maintenance of sinus rhythm by catheter ablation can improve LVEF in patients with TIC due to atrial fibrillation (AF). Beta-blockers are mandatory for the treatment of heart failure with reduced LVEF(HFrEF), but the necessity of beta-blockers in TIC patients even after catheter ablation remains unclear. We examined the effect of beta-blockers on cardiac function in TIC patients after catheter ablation. We retrospectively analyzed 124 patients with a history of heart failure and an LVEF of ≤ 50% who underwent catheter ablation for AF. TIC was defined as a ≥ 10% improvement in the baseline LVEF and an improvement to an LVEF of ≥ 50% at 6months after ablation. Patients with other cardiomyopathy diagnosed before the ablation were excluded. LVEF was significantly increased with the reductions of the left ventricular and left atrial volumes at the 6-month follow-up in all 80 patients with TIC. No beta-blockers were prescribed during the post-ablation follow-up in 21 patients with TIC. The absolute values of and changes in the echocardiographic parameters between before and after ablation were not significantly different between patients with and without beta-blockers after the ablation. A simple score using the history of hospitalization for heart failure and use of beta-blockers or diuretics prior to ablation was useful in identifying TIC patients who did not need prescription of beta-blockers after catheter ablation. LVEF similarly improved in both patients with and without prescription of beta-blockers after the ablation. Beta-blockers may not need to be prescribed after successful catheter ablation for AF in LVEF of ≤ 50% patients without other cause of cardiomyopathy diagnosed before the ablation, a history of hospitalization for heart failure and prescription of beta-blockers and diuretics before the ablation.

Pulmonary hypertension in patients with heart failure with reduced ejection fraction: impact of the new definition of pulmonary hypertension

Abstract Background Prevalence, haemodynamic character, and associated factors of pulmonary hypertension (PH) in heart failure with reduced left ventricular ejection fraction (HFrEF) according to the 2022 European Society of Cardiology (ESC) PH definition remain unclear. Purpose To describe the prevalence of PH and its phenotypes in patients with advanced HFrEF according to the 2022 PH definition and analyse characteristics of the respective PH groups. Methods We retrospectively analysed 175 consecutive patients (pts) (136 men) with advanced HFrEF referred to a single centre. All pts underwent right heart catheterization (RHC). We identified pts with post-capillary PH which was defined as mean pulmonary artery pressure (mPAP) > 20 mm Hg and pulmonary artery wedge pressure (PAWP) > 15 mm Hg. Pts with mPAP ≤ 20 mm Hg and/or PAWP ≤ 15 mm Hg were labelled as pts without post-capillary PH. According to pulmonary vascular resistance (PVR), PH was further classified as isolated post-capillary (IPC PH) (PVR ≤ 2 Wood units) or combined post- and pre-capillary PH (CPC PH) (PVR ≤ 2 Wood units). We compared selected demographic, clinical, echocardiographic, laboratory, and haemodynamic parameters between the individual groups. Results Median age of the pts was 54 (18-69) years and mean left ventricular ejection fraction (LVEF) 21.9 ± 6.7 %. Out of 175 pts included, 146 (83 %) pts had post-capillary PH. Twenty-nine (17%) pts did not meet the post-capillary PH criteria. Thirty-five (20%) pts had IPC PH and 111 (63%) pts CPC PH. In comparison with the pts without post-capillary PH, pts with post-capillary PH had longer history of HFrEF (6.8 ± 5.6 vs 3.8 ± 4.6 years, p<0.01), lower systolic blood pressure (108 ± 13 vs 120 ± 20 mmHg, p<0.01), lower LVEF (21 ± 6 vs 26 % ± 8 p<0.001), larger left atrial diameter (51 ± 7 vs 45 ± 7 mm, p<0.001), right ventricular diameter (39 ± 9 vs 34 ± 8 mm, p<0.01), higher prevalence of renal insufficiency (29 vs 59%, p<0.05) and atrial fibrillation (12 vs 0 %, p<0.05), and higher natriuretic peptide levels (4565 ± 4087 vs 1976 ± 2376 pg/mL, p<0.001). Patients with CPC PH were older (54 ± 10 vs 47 ± 13 years, p < 0.001), had lower 6-minute walking distance (390 ± 126 vs 439 ± 74 years, p<0.05), higher prevalence of renal insufficiency (33 vs 14 %, p<0.05), and diabetes mellitus (32 vs 11 % p<0.05) than pts with IPC PH. Alteration in pulmonary haemodynamics was more pronounced in CPC PH than IPC PH, with higher mPAP (40 ± 9 vs 29 ± 5 mm Hg, p<0.001), PAWP (27 ± 6 vs 22 ± 5 mm Hg, p<0.001), and lower cardiac index (1.9 ± 0.4 vs 2.3 ± 0.5 L/min/m2, p<0.001). Conclusion Post-capillary PH according to 2022 definition is frequent in pts with advanced HFrEF, with CPC PH prevalence three times as high as in ICP PH. Despite lowering both the threshold for presence of PH and pre-capillary component in the recent definition, PH and CPC PH still seem to reflect a more advanced stage of HFrEF.

Characterization and prognostic impact of ischemic etiology in heart failure with reduced left ventricular ejection fraction

Abstract Introduction and objectives Ischemic heart disease is the cause of 50-60% of cases of heart failure with reduced left ventricular ejection fraction (HF-rEF). The impact of ischemic etiology on left ventricular ejection fraction (LVEF) improvement and prognosis remains unclear. Our main objective was to analyze the differential clinical profile between ischemic and non-ischemic etiology, as well as its medium-to-long term prognosis. Methods Prospective study of a cohort of patients with HF-rEF in real clinical practice. A comparative analysis was performed between patients with HF-rEF of non-ischemic etiology (Group 1) and ischemic etiology (Group 2). Clinical, analytical, echocardiographic and therapeutic variables were analyzed, and the medium-to-long term impact in terms of mortality and hospital readmissions for HF was evaluated. Results 409 patients were analyzed. 276 patients (67.5%) had non-ischemic etiology and 133 patients (32.5%) had ischemic etiology. Group 2 was older (65.8±13.3vs70.8±10.3;p<0.001), more men (68.1%vs86.5%;p<0.001), higher prevalence of arterial hypertension (62.3%vs76.7%;p = 0.004), diabetes mellitus (38.8%vs67.7%; p<0.001), dyslipemia (52.4%vs82.7%;p<0.001), chronic kidney disease (34.4%vs56.4%;p<0.001), anemia (24.3%vs47.4%;p<0.001) and vascular comorbidity (25.7%vs54.9%;p<0.001) and lower prevalence of atrial fibrillation (56.2%vs44.4%;p = 0.025). In Group 2 there was a lower proportion of de novo HF (60.1%vs45.1%;p = 0.004) with longer HF evolution time (24.4±48.8vs61.5±89.3; p<0.001), a lower proportion of patients improving LVEF at follow-up (51.6%vs21.1%;p<0.001) and a higher baseline NTproBNP concentration [4463(IQR 1976-10431)vs5746(IQR 2336.5-13789);p = 0.039]. Regarding baseline treatment, in Group 1 there was a higher prescription of mineralocorticoid receptor antagonists (78.3%vs63.9%;p = 0.002) and less ICD implantation (6.5vs14.3%;p = 0.01), with no differences in the rest of the treatment. With a mean follow-up of 60 months, Group 2 had a higher readmission rate (39%vs50.3%;p<0.01) and higher HF mortality (26.8%vs41%;p<0.01), with differences from early stages. Conclusions Patients with HF-rEF of ischemic etiology associate a greater number of comorbidities, a lower percentage of de novo HF, longer time of HF evolution, lower percentage of LVEF improvement and higher baseline NTproBNP.

Heart Failure: Recent Advances and Breakthroughs

Heart failure (HF) is a common clinical condition encountered in various healthcare settings with a vast socioeconomic impact. Recent advancements in pharmacotherapy have led to the evolution of novel therapeutic agents with a decrease in hospitalization and mortality rates in HF with reduced left ventricular ejection fraction (HFrEF). Lately, the introduction of artificial intelligence (AI) to construct decision-making models for the early detection of HF has played a vital role in optimizing cardiovascular disease outcomes. In this review, we examine the newer therapies and evidence behind goal-directed medical therapy (GDMT) for managing HF. We also explore the application of AI and machine learning (ML) in HF, including early diagnosis and risk stratification for HFrEF.

Short-Term Changes in Peak VO2 After Initiation of Dapagliflozin in Heart Failure Across Iron Status

BackgroundSome studies have indicated that sodium-glucose cotransporter-2 (SGLT2) inhibitors promote an increase in cell iron use. ObjectivesThe aim of this study was to examine, in patients with stable heart failure with reduced left ventricular ejection fraction (HFrEF), the effect of dapagliflozin on ferrokinetic parameters and whether short-term changes in peak oxygen consumption (Vo2) after dapagliflozin treatment are influenced by baseline and serial ferrokinetic status. MethodsThis was an exploratory analysis of a randomized, double-blind clinical trial that evaluated the effect of dapagliflozin vs placebo on peak Vo2 in patients with HFrEF (NCT04197635) and included 76 of the 90 patients initially enrolled in the trial. Changes in peak Vo2 at 1 and 3 months were explored according to baseline and longitudinal ferrokinetic parameters (natural logarithm [ln] ferritin, transferrin saturation index [TSAT], soluble transferrin receptor, and hepcidin). Linear mixed-effect regression was used for the analyses. ResultsCompared with placebo, dapagliflozin led to a significant decrease in 3-month ln ferritin (P = 0.040) and an increase in 1-month ln soluble transferrin receptor (P = 0.023). Between-treatment comparisons revealed a stepwise increase in peak Vo2 in the dapagliflozin group at 1 and 3 months, which was especially apparent at lower baseline values of TSAT and ferritin (P < 0.05). Lower time-varying values of TSAT (1 and 3 months) also identified patients with greater improvements in peak Vo2. ConclusionsIn patients with stable HFrEF, treatment with dapagliflozin resulted in short-term increases in peak Vo2, which were most marked in patients with surrogates of greater iron deficiency at baseline and during treatment. (Short-Term Effects of Dapagliflozin on Peak Vo2 in HFrEF [DAPA-VO2]; NCT04197635)

Exercise oscillatory ventilation in patients with coexisting chronic obstructive pulmonary disease and heart failure: Clinical implications

BackgroundExercise oscillatory ventilation (EOV) is considered an important variable for predicting poor prognosis in patients with heart failure (HF) with reduced left ventricular ejection fraction (HFrEF). However, there are no studies evaluating EOV presence in the coexistence chronic obstructive pulmonary disease (COPD) and HFrEF. Aims: I) To compare the clinical characteristics of participants with coexisting HFrEF-COPD with and without EOV during cardiopulmonary exercise testing (CPET); and II) to identify the impact of EOV on mortality during follow-up for 35 months. Methods50 stable HFrEF-COPD (EF<50%) participants underwent CPET and were followed for 35 months. The parametric Student's t-test, chi-square tests, linear regression model and Kaplan-Meier analysis were applied. ResultsWe identified 13 (26%) participants with EOV and 37 (74%) without EOV (N-EOV) during exercise. The EOV group had worse cardiac function (LVEF: 30 ± 6% vs. N-EOV 40 ± 9%, p = 0.007), worse pulmonary function (FEV1: 1.04 ± 0.7 L vs. N-EOV 1.88 ± 0.7 L, p = 0.007), a higher mortality rate [7 (54%) vs. N-EOV 8 (27%), p = 0.02], higher minute ventilation/carbon dioxide production (V̇˙E/ V̇˙ CO2) slope (42 ± 7 vs. N-EOV 36 ± 8, p = 0.04), reduced peak ventilation (L/min) (26.2 ± 16.7 vs. N-EOV 40.3 ± 16.4, p = 0.01) and peak oxygen uptake (mlO2 kg−1 min−1) (11.0 ± 4.0 vs. N-EOV 13.5 ± 3.4 ml●kg−1●min−1, p = 0.04) when compared with N-EOV group. We found that EOV group had a higher risk of mortality during follow-up (long-rank p = 0.001) than patients with N-EOV group. ConclusionThe presence of EOV is associated with greater severity of coexisting HFrEF and COPD and a reduced prognosis. Assessment of EOV in participants with coexisting HFrEF-COPD, as a biomarker for both clinical status and prognosis may therefore be warranted.

Short-term anti-remodeling effects of gliflozins in diabetic patients with heart failure and reduced ejection fraction: an explainable artificial intelligence approach.

Introduction: Sodium-glucose cotransporter type 2 inhibitors (SGLT2i), gliflozins, play an emerging role for the treatment of heart failure with reduced left ventricular ejection fraction (HFrEF). Nevertheless, the effects of SGLT2i on ventricular remodeling and function have not been completely understood yet. Explainable artificial intelligence represents an unprecedented explorative option to clinical research in this field. Based on echocardiographic evaluations, we identified some key clinical responses to gliflozins by employing a machine learning approach. Methods: Seventy-eight consecutive diabetic outpatients followed for HFrEF were enrolled in the study. Using a random forests classification, a single subject analysis was performed to define the profile of patients treated with gliflozins. An explainability analysis using Shapley values was used to outline clinical parameters that mostly improved after gliflozin therapy and machine learning runs highlighted specific variables predictive of gliflozin response. Results: The five-fold cross-validation analyses showed that gliflozins patients can be identified with a 0.70 ± 0.03% accuracy. The most relevant parameters distinguishing gliflozins patients were Right Ventricular S'-Velocity, Left Ventricular End Systolic Diameter and E/e' ratio. In addition, low Tricuspid Annular Plane Systolic Excursion values along with high Left Ventricular End Systolic Diameter and End Diastolic Volume values were associated to lower gliflozin efficacy in terms of anti-remodeling effects. Discussion: In conclusion, a machine learning analysis on a population of diabetic patients with HFrEF showed that SGLT2i treatment improved left ventricular remodeling, left ventricular diastolic and biventricular systolic function. This cardiovascular response may be predicted by routine echocardiographic parameters, with an explainable artificial intelligence approach, suggesting a lower efficacy in case of advanced stages of cardiac remodeling.

Prognostic significance of addition of electrocardiographic findings to the MAGGIC heart failure risk score

Abstract Funding Acknowledgements Type of funding sources: None. Main funding source(s): Researchers Background The Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) is a scoring system that is easy to use in outpatient or inpatient settings and was developed to predict the survival of heart failure (HF) patients after hospitalization. Aim This study aims to determine the prognostic significance of MAGGIC risk score combined with electrocardiography (ECG) parameters in decompensated patients with heart failure with reduced left ventricular ejection fraction (HFrEF) who were hospitalized for worsening HF. Methods A total of 562 HF patients with New York Heart Association (NYHA) II-IV functional class who were discharged after hospitalization for decompensated HF between 2013 and 2018 in a single center were included. MAGGIC risk scores of all participating patients were calculated according to baseline characteristics gathered using data from the initial hospitalization for HF. In addition, electrocardiographic findings of all patients were examined. Results During the follow-up period (4.5 ± 1.2 years) 177 patients died. MAGGIC scores were observed to be higher in non-survivors compared to surviving patients (28.69 ± 7.01 vs. 22.82 ± 6.05, p &amp;lt; 0.001). After a multivariate analysis, MAGGIC score (OR:1.090, p &amp;lt; 0.001), development of cardio-renal syndrome (OR:2.035, p &amp;lt; 0.001), presence of left bundle branch block (LBBB) (OR:1.931, p &amp;lt; 0.001), atrial fibrillation (AF) (OR:1.817, p &amp;lt; 0.001), and fragmented QRS (fQRS) (OR:1.671, p = 0.002) on ECG were found to be independent predictors of mortality. While the MAGGIC score was shown to predict mortality (AUC = 0.739), its predictive power was improved when combined with AF (AUC = 0.752), LBBB (AUC = 0.745), and fQRS (AUC = 0.757) respectively, as well as in the combined final model (MAGGIC score, AF, LBBB, fQRS) (AUC = 0.787). Conclusions Our findings showed that addition of electrocardiographic findings to the MAGGIC heart failure risk score has prognostic significance in decompensated patients with HFrEF.

Muscle sympathetic nerve activity and adaptive servo-ventilation: questions remain

Sudden cardiac death presumably due to cardiac arrhythmias is one of the hypotheses to explain the observed higher cardiovascular mortality in the adaptive servo-ventilation (ASV) group of the SERVE-HF study [1, 2]. In this regard, we congratulate Tamisier et al . [3] for their efforts to clarify the effect of ASV on muscle sympathetic nerve activity (MSNA) in patients with central sleep apnoea (CSA) and heart failure with reduced left ventricular ejection fraction (HFrEF). Analysing data from an SERVE-HF ancillary study, they concluded that: 1) suppression of CSA with ASV did not seem to have a significant effect on chronic HFrEF-related sympathetic activation; and 2) simultaneous suppression of CSA and reduction in MSNA was associated with increased cardiovascular mortality. In our opinion, these conclusions might be different if some confounding factors were considered. Stratified analyses of ongoing trials will need to take adaptive servo-ventilation (ASV) efficacy into account before concluding on ASV impact on outcome measures https://bit.ly/3GpHAD4

Treatment response in recent-onset heart failure with reduced ejection fraction: non-ischaemic vs. ischaemic aetiology.

In heart failure (HF) with reduced left ventricular ejection fraction (HFrEF), the prognosis appears better in non-ischaemic than in ischaemic aetiology. Infrequent diagnostic work-up for ischaemic heart disease (IHD) in HF is reported. In this study, we compared short-term response to initiated guideline-directed medical treatment (GDMT) in recent-onset HFrEF of non-ischaemic (non-IHF) vs. ischaemic (IHF) aetiology and evaluated the frequency of coronary investigation. Patients hospitalized with recent-onset HFrEF [left ventricular ejection fraction (LVEF)<40%] between 1 January 2016 and 31 December 2019 were included. Treatment response was determined by use of a hierarchical clinical composite outcome classifying each patient as worsened, improved, or unchanged based on hard outcomes (mortality, heart transplantation, and HF hospitalization) and soft outcomes (±≥10 unit change in LVEF, ±≥30% change in N-terminal pro-B-type natriuretic peptide, and ±≥1 point change in New York Heart Association functional class) during 28weeks of follow-up. The associations between baseline characteristics and composite changes were analysed with multiple logistic regression. Among the 364 patients analysed, 47 were not investigated for IHD. Comparing non-IHF (n=203) vs. IHF (n=114), patients were younger (mean age 61.0 vs. 69.4years, P<0.001) with lower mean LVEF (26% vs. 31%, P<0.001), but with similar male predominance (70.4% vs. 75.4%, P=0.363). For non-IHF vs. IHF, the composite outcomes were worsened (19.1% vs. 43.9%, P<0.001) and improved (74.2% vs. 43.9%, P<0.001). After multivariable adjustments, IHF was associated with increased odds for worsening [odds ratio (OR) 2.94; 95% confidence interval (CI) 1.51-5.74; P=0.002] and decreased odds for improvement (OR 0.35; 95% CI 0.18-0.65; P<0.001). In cases without previous IHD or new-onset myocardial infarction (n=261), a decision for coronary investigation was made in 69.0%. In recent-onset HFrEF, patients with non-IHF responded better to GDMT than patients with IHF. Almost one-third of patients selected for follow-up at HF clinics were never investigated for IHD.

Disease progression of heart failure in type 2 diabetes patients in Germany; a real world data analysis using health insurance claims data

Abstract Individuals with Type 2 Diabetes (T2D) show two- to four-fold increased risk of Heart failure (HF). Given the increasing T2D prevalence in Germany, researching the interaction of T2DM and HF is of high importance. HF still progresses rapidly. Left ventricular ejection fraction (LVEF) plays an important role in understanding disease progression. Commonly, LVEF is being distinguished into three categories: HF with preserved LVEF (HFpEF), HF with moderate reduced LVEF (HFmEF) and HF with reduced LVEF (HFrEF). In Germany there are no recent data on disease progression in HF especially according to LVEF categories. Purpose of this study is to a) measure how many T2DM patients acquire HF over two years; b) understand the progression of HF in these patients in a five-year follow-up; and c) visualize disease progression with Sankey plots. We used insurance claims data from German Statutory Health Insurances (SHI). As LVEF category is not included in these data, a model was used to classify patients into HFrEF or HFpEF (with omitting the HFmEF category due to better statistical performance of a binary model). The model was derived from a set of 34 proxy variables (disease coding, interventions, drug prescriptions). Selection period for T2D patients is 2013. Inclusion period was 2014–2015, follow-up 2016–2020. Baseline characteristics include demographic data, disease stage, comorbidities, and risk factors. Follow-up criteria were MACE (including hospital admission) changes in LVEF category and mortality. 173,195 individuals with T2D were identified in 2013, median age 66 yrs. 6,725 (3.88% of the overall sample) developed HF in 2014 or 2015, median age 74 yrs. As Sankey plot visualizations show, 34.4% of the patients had MACE over the course of five years; 24.5% were still alive and 9.9% died from CV-death. Further 33% died of other causes. Myocardial infarct was the most common MACE, followed by stroke (32%), hospital admission for HF (28%) and CV death (7%). 40% of patients were never admitted to a hospital over the study period. Exploratory analyses identified 5,282 HFpEF patients (78.54%) and 1,443 HFrEF patients (21.46%). Survival after 5 years in HFpEF patients was 71%, in HFrEF patients 29%. After five years 3,430 (90%) surviving patients were still in HFpEF and 399 (10%) in HFrEF. This analysis provides disease progression insights in T2D patients who developed HF in Germany. The sample is representative for the country and numbers can be extrapolated to the overall German SHI population. A significant number of patients die within 5 years of initial diagnosis. As echo diagrams are not available in German insurance claims, validity of the predicted LVEF cannot be assessed. Further research featuring real world LVEF score validation would be highly desirable. Beyond therapeutic care, digital solutions for closer monitoring of these patients may improve the outcome of these patients. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Sanofi

Does a normal electrocardiogram exclude heart failure with reduced left ventricular ejection fraction?

Abstract Background In the ESC guidelines for chronic heart failure an electrocardiogram (ECG) is part of the diagnostic set-up (1). A normal ECG makes the diagnosis unlikely. But can a normal ECG exclude heart failure with reduced left ventricular ejection fraction (HFrEF) and be a gatekeeper to echocardiography? Methods Patients referred from primary care to the cardiac outpatient clinic with suspicion of heart failure were consecutively included in the study, during a period of one year. With the referral from primary care was included an ECG which was assessed by a senior cardiologist and divided into two groups: 1) Patients with normal ECG; 2) Patients with pathologically ECG. Subsequently, an echocardiographic examination was performed in a blinded fashion and left ventricular ejection fraction (LVEF) was measured. Results Overall, 403 patients were included in the study. A normal ECG was present in 155 (38%) patients and a pathological ECG was present in 248 (62%) patients. In total, an echocardiographic examination identified 55 (14%) patients with an LVEF below 60% and 33 patients (8%) with LVEF below 50%. In patients with a normal ECG, only two patients had heart failure with a mildly reduced ejection fraction (41–49%), Figure 1. Thus, the ECG had a sensitivity of 94% and a negative predictive value of 99%, Figure 2. Conclusion A normal electrocardiogram has a high diagnostic sensitivity and negative predictive value for excluding heart failure with reduced LVEF and could be a gatekeeping tool in the prioritization of patients referred to echocardiography examination from primary care. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): Department of Cardiovascular research, OUH, Svendborg Hospital

Revisiting a Prognosticating Algorithm from Cardiopulmonary Exercise Testing in Chronic Heart Failure (from the MECKI Score Population)

Cardiopulmonary exercise testing is a prognostic tool in heart failure with reduced left ventricular ejection fraction (HFrEF). Prognosticating algorithms have been proposed, but none has been validated. In 2017, a predictive algorithm, based on peak oxygen consumption (VO2), ventilatory response to exercise (ventilation [VE] carbon dioxide production [VCO2], the VE/VCO2 slope), exertional oscillatory ventilation (EOV), and peak respiratory exchange ratio, was recommended, according treatment with β blockers: patients with HFrEF registered in the metabolic exercise test data combined with cardiac and kidney indexes (MECKIs) database were used to validated this algorithm. According to the inclusion/exclusion criteria, 4,683 MECKI patients with HFrEF were enrolled. At 3years follow-up, the end point was cardiovascular death and urgent heart transplantation (cardiovascular events [CV]). CV events occurred in 25% in patients without β blockers, whereas those with β-blockers had 11% (p <0.0001). In patients without β blockers, 36%, 24%, and 7% CV events were observed in those with peak VO2 ≤10, with peak VO2 >10 <18, and with peak VO2 ≥18ml/kg/min (p=0.0001), respectively; in MECKI patients with peak VO2 ≤10 and patients with intermediate exercise capacity, a peak respiratory exchange ratio (≥1.15) and VE/VCO2 slope (≥35) were diriment, respectively (p=0.0001). EOV, when occurred, increased risk. In MECKI patients on β blockers, 29%, 17%, and 8% CV events were noticed in those with a peak VO2 ≤8, with peak VO2=8 to 12, and patients with peak VO2 ≥12ml/kg/min, respectively (p=0.0000); when EOV was monitored an increment of risk was witnessed. In conclusion, the outcome of this algorithm was confirmed with the MECKI cohort.

Effects of trimetazidine in patients with severe chronic heart failure with reduced left ventricular ejection fraction: A prospective, randomized, open-label, cross-over study.

BackgroundTrimetazidine (TMZ) modulates cardiac metabolism, but its use in heart failure remains controversial. The aim of the study was to evaluate the effects of TMZ on exercise capacity, left ventricular ejection fraction (LVEF), mortality, and quality of life in stable patients with heart failure with reduced left ventricular ejection fraction (HFrEF).MethodsForty-five patients with stable advanced HFrEF treated with optimal medical therapy were randomized in a prospective, single-center, open-label, cross-over study of TMZ (35 mg b.i.d.) on top of standard medical therapy or standard pharmacotherapy for two periods of 30 days and one period of 6 months. Initially and at the end of each period all patients underwent the following: exercise testing, six-minute walk test (6MWT), two-dimensional-echocardiography, and quality of life assessment.ResultsThe mean age of patients was 58.2 ± 10.6 years. Etiology of HFrEF was ischemic in 66.6% of patients. After 6 months no significant changes were observed in either group with regards to peak VO2 uptake, 6MWT, LVEF, or quality of life. TMZ had no effect on mortality or cardiovascular events.ConclusionsThe additional use of TMZ on top of standard medical therapy in stable advanced HFrEF patients was not associated with significant changes in mortality, exercise capacity, LVEF, or quality of life.

Exercise oscillatory breathing in heart failure with reduced ejection fraction: clinical implication.

The aim of the study is (i) to evaluate the impact of exercise oscillatory ventilation (EOV) in patients with heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) during cardiopulmonary exercise testing (CPET) compared with no EOV (N-EOV); (ii) to identify the influence of EOV persistence (P-EOV) and EOV disappearance (D-EOV) during CPET on the outcomes of mortality and hospitalization in HFrEF patients; and (iii) to identify further predictors of mortality and hospitalization in patients with P-EOV. Three hundred and fifteen stable HFrEF patients underwent CPET and were followed for 35 months. We identified 202 patients N-EOV and 113 patients with EOV. Patients with EOV presented more symptoms [New York Heart Association (NYHA) III: 35% vs. N-EOV 20%, P &lt; 0.05], worse cardiac function (LVEF: 28 ± 6 vs. N-EOV 39 ± 1, P &lt; 0.05), higher minute ventilation/carbon dioxide production (V̇E/V̇CO2 slope: 41 ± 11 vs. N-EOV 37 ± 8, P &lt; 0.05) and a higher rate of deaths (26% vs. N-EOV 6%, P &lt; 0.05) and hospitalization (29% vs. N-EOV 9%, P &lt; 0.05). Patients with P-EOV had more severe HFrEF (NYHA IV: 23% vs. D-EOV: 9%, P &lt; 0.05), had worse cardiac function (LVEF: 24 ± 5 vs. D-EOV: 34 ± 3, P &lt; 0.05) and had lower peak oxygen consumption (V̇O2) (12.0 ± 3.0 vs. D-EOV: 13.3 ± 3.0 mLO2 kg-1.min-1, P &lt; 0.05). Among P-EOV, other independent predictors of mortality were V̇E/V̇CO2 slope ≥36 and V̇O2 peak ≤12 mLO2 kg-1 min-1; a V̇E/V̇CO2 slope≥34 was a significant predictor of hospitalization. Kaplan-Meier survival analysis showed that HFrEF patients with P-EOV had a higher risk of mortality and higher risk of hospitalization (P &lt; 0.05) than patients with D-EOV and N-EOV. In HFrEF patients, EOV persistence during exercise had a strong prognostic role. In P-EOV patients, V̇E/V̇CO2 ≥36 and V̇O2 peak ≤12 mLO2 kg-1 min-1 had a further additive negative prognostic role.

META-ANALYSIS OF DEDICATED HEART FAILURE TRIALS EVALUATING THE EFFECT OF SACUBITRIL/VALSARTAN ON MAJOR CARDIAC RHYTHM DISORDERS

Objective: The important role of major cardiac rhythm disorders in the prognosis of subjects with heart failure (HF) has been discussed extensively. Sacubitril/valsartan has revolutionized treatment strategy for patients with HF with reduced left ventricular ejection fraction (HFrEF), while it is cardiovascular safe -but not efficacious- in patients with HF with preserved ejection fraction (HFpEF). Anti-arrhythmogenic effect of sacubitril/valsartan has been demonstrated in several, recent experimental studies, however the clinical implications of that observations remain largely unknown. Design and method: We sought to determine the effect of sacubitril/valsartan compared to active comparator on major cardiac rhythm disorders in patients with HF, pooling data from the dedicated HF outcome trials. We evaluated the following outcomes of interest: atrial fibrillation, atrial flutter, ventricular tachycardia, ventricular fibrillation and cardiac arrest. The latter outcome was assessed in the light of recent evidence that arrhythmias account for almost 7% of cardiac arrest cases, both in in-hospital and out-of-hospital settings. Results: We pooled data from 3 trials in a total of 14,128 enrolled subjects with HF regardless of LVEF, assigned either to sacubitril/valsartan or valsartan.Sacubitril/valsartan compared to valsartan alone did not result in a significant risk reduction for atrial fibrillation (RR = 1.05, 95% CI; 0.89–1.24, I2 = 0%), atrial flutter (RR = 1.01, 95% CI; 0.55–1.86, I2 = 34%), ventricular tachycardia (RR = 0.92, 95% CI; 0.53–1.58, I2 = 32%) and ventricular fibrillation (RR = 0.79, 95% CI; 0.47–1.32, I2 = 0%). However, we demonstrated that sacubitril/valsartan compared to valsartan conferred a significant risk reduction in cardiac arrest by 47% (RR = 0.53, 95% CI; 0.38–0.76, I2 = 0%). Conclusions: Therefore, despite the cardiovascular efficacy and safety of sacubitril/valsartan among patients with HF, and its established role in the treatment of patients with HFrEF, it does not prevent major cardiac arrhythmias. However, its preventive role against cardiac arrest is of utmost importance and should be assessed in future randomized controlled trials as a surrogate outcome.

Outcomes and Predictors of Mortality Among Cardiac Intensive Care Unit Patients With Heart Failure

BackgroundLittle is known regarding the causes of critical illness and determinants of prognosis of patients with heart failure (HF) admitted to the modern cardiac intensive care unit (CICU). We sought to describe the epidemiology and outcomes of patients with HF admitted to the contemporary CICU. Methods and ResultsRetrospective cohort analysis of Mayo Clinic CICU patients admitted with HF from 2007 to 2018 who had left ventricular ejection fraction (LVEF) data. HF with reduced LVEF (HFrEF) was defined as a LVEF of less than 50%, and HF with preserved LVEF (HFpEF) as a LVEF of 50% or greater. In-hospital mortality was analyzed using multivariable logistic regression. Survival to 1 year was analyzed using a Kaplan–Meier analysis. We included 4012 patients, including 67.8% with HFrEF and 32.2% with HFpEF. Patients with HFrEF and HFpEF were comparable and had equivalent severity of illness. Critical care therapies were used in 59.4%, with a slight preponderance in patients with HFrEF. In-hospital mortality occurred in 12.5% of patients and was similar in HFrEF vs HFpEF. Shock and cardiac arrest were the strongest predictors of adjusted in-hospital mortality, followed by Braden skin score and serum chloride level; patients with HFrEF and HFpEF had similar adjusted mortality rates. The 1-year survival after hospital discharge was 74.5% and was slightly lower for patients with HFpEF. All-cause rehospitalization occurred in 36.6%, and 52.8% of hospital survivors died or were readmitted within 1 year. ConclusionsCICU patients with HF have a substantial burden of critical illness, high use of critical care therapies, and poor outcomes regardless of LVEF. This finding emphasizes the potential unmet care needs in this cohort. Lay summaryPatients with heart failure who require admission to the cardiac intensive care unit have high severity of illness and are at significant risk of death during and after hospitalization. These patients often require specialized critical care therapies to treat manifestations of critical illness. Patients who are admitted with cardiac arrest or shock, including those who require mechanical ventilation or vasopressors, are at particularly high risk of death. Patients’ left ventricular ejection fraction is not strongly associated with the risk of death when accounting for other major predictors including frailty and laboratory abnormalities.

Prognostic significance of addition of electrocardiographic findings to the MAGGIC heart failure risk score

BackgroundThe Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) is a scoring system that is easy to use in outpatient or inpatient settings and was developed to predict the survival of heart failure (HF) patients after hospitalization. AimThis study aims to determine the prognostic significance of MAGGIC risk score combined with electrocardiography (ECG) parameters in decompensated patients with heart failure with reduced left ventricular ejection fraction (HFrEF) who were hospitalized for worsening HF. MethodsA total of 562 HF patients with New York Heart Association (NYHA) II-IV functional class who were discharged after hospitalization for decompensated HF between 2013 and 2018 in a single center were included. MAGGIC risk scores of all participating patients were calculated according to baseline characteristics gathered using data from the initial hospitalization for HF. In addition, electrocardiographic findings of all patients were examined. ResultsDuring the follow-up period (4.5 ± 1.2 years) 177 patients died. MAGGIC scores were observed to be higher in non-survivors compared to surviving patients (28.69 ± 7.01 vs. 22.82 ± 6.05, p < 0.001). After a multivariate analysis, MAGGIC score (OR:1.090, p < 0.001), development of cardio-renal syndrome (OR:2.035, p < 0.001), presence of left bundle branch block (LBBB) (OR:1.931, p < 0.001), atrial fibrillation (AF) (OR:1.817, p < 0.001), and fragmented QRS (fQRS) (OR:1.671, p = 0.002) on ECG were found to be independent predictors of mortality. While the MAGGIC score was shown to predict mortality (AUC = 0.739), its predictive power was improved when combined with AF (AUC = 0.752), LBBB (AUC = 0.745), and fQRS (AUC = 0.757) respectively, as well as in the combined final model (MAGGIC score, AF, LBBB, fQRS) (AUC = 0.787). ConclusionsOur findings showed that addition of electrocardiographic findings to the MAGGIC heart failure risk score has prognostic significance in decompensated patients with HFrEF.

ARNI in HFrEF-One-Centre Experience in the Era before the 2021 ESC HF Recommendations.

Background: Sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor (ARNI), has demonstrated a survival benefit and reduces heart failure hospitalization in patients with heart failure with reduced left ventricular ejection fraction (HFrEF); however, our experience in this field is limited. This study aimed to summarize a real clinical practice of the use of ARNI in HFrEF patients hospitalized due to HFrEF in the era before the 2021 ESC HF recommendations, as well as assess their clinical outcome with regard to ARNI administration. Methods and Materials: Overall, 613 patients with HFrEF hospitalized in 2018–2020 were enrolled into a retrospective one-centre cross-sectional analysis. The study population was categorized into patients receiving (82/13.4%) and not-receiving (531/82.6%) ARNI. Clinical outcomes defined as rehospitalization, number of rehospitalizations, time to the first rehospitalization and death from any cause were analysed in the 1–2 year follow-up in the ARNI and non-ARNI groups, matched as to age and LVEF. Results: Clinical characteristics revealed the following differences between ARNI and non-ARNI groups: A higher percentage of cardiovascular implantable electronic devices (CIED) (p = 0.014) and defibrillators with cardiac resynchronization therapy (CRT-D) (p = 0.038), higher frequency of atrial fibrillation (p = 0.002) and history of stroke (p = 0.024) were in the ARNI group. The percentage of patients with HFrEF NYHA III/IV presented an increasing trend to be higher in the ARNI (64.1%) as compared to the non-ARNI group (51.5%, p = 0.154). Incidence of rehospitalization, number of rehospitalizations and time to the first rehospitalization were comparable between the groups. There were no differences between the numbers of deaths of any cause in the ARNI (28%) and non-ARNI (28%) groups. The independent negative predictor of death in the whole population of ARNI and non-ARNI groups was the coexistence of coronary artery disease (CAD) (beta= −0.924, HR 0.806, p = 0.011). Conclusions: Our current positive experience in ARNI therapy is limited to extremely severe patients with HFrEF. Regardless of the more advanced HF and HF comorbidities, the patients treated with ARNI presented similar mortality and rehospitalizations as the patients treated by standard therapy.