Heart Failure With Reduced Left Ventricular Ejection Fraction Patients Research Articles

Mesenchymal stromal cells to treat patients with non-ischaemic heart failure: Results from SCIENCE II pilot study.

Allogeneic stem cell therapy is more logistically suitable compared with autologous cell therapy for large-scale patient treatment. We aim to investigate the clinical safety and efficacy profile of the allogeneic adipose tissue derived mesenchymal stromal cell product (CSCC_ASC) as an add-on therapy in patients with chronic non-ischaemic heart failure with reduced left ventricular ejection fraction (HFrEF)<40%. This is a single-centre investigator-initiated randomized phase I/II study with direct intra-myocardial injections of 100 million allogeneic CSCC_ASC. A total of 30 HFrEF patients with New York Heart Association (NYHA) class ≥II despite optimal anticongestive heart failure medication and plasma NT-proBNP>300pg/mL (>35pmol/L) were included and randomized 2:1 to CSCC_ASC or standard care. The primary endpoint left ventricular end systolic volume (LVESV) and other echo related parameters were analysed by an investigator blinded for treatment allocation. No difference in serious adverse events was observed between groups. LVESV decreased significantly from baseline to 6months follow-up in the ASC group (153.7±53.2mL and 128.7±45.6mL, P<0.001) and remained unchanged in the standard care group (180.4±39.4mL and 186.7±48.9mL, P=0.652). There was a significant difference between the groups in LVESV change (31.3±11.0mL, P=0.009). The difference from baseline to follow-up between the two groups in left ventricular end diastolic volume (LVEDV) was 18.7±12.4mL, P=0.146 and in left ventricular ejection fraction (LVEF) -7.8±2.1%, P=0.001. Considering the baseline values of LVESV, LVEDV and LVEF as covariates, the difference between groups for change from baseline to follow-up resulted in a P-value of 0.056, 0.076, and 0.738, respectively. NYHA class and self-reported health did also improve significantly in the ASC group compared with the standard care group (0.7±0.2, P=0.001 and -12.8±5.3, P=0.025; respectively). There was no difference in NT-proBNP (-371±455pmol/L, P=0.422) or in 6min walk test (12±31m, P=0.695) between groups. Intramyocardial injections of allogeneic CSCC_ASC in patients with chronic non-ischaemic HFrEF was safe and improved LVESV, LVEF, NYHA class, and self-reported health compared with standard care group.

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

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.

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.

M16. The potential role of pentraxin-3 as prognostic factor to predict outcome in heart failure patients with reduced left ventricular ejection fraction: a meta-analysis study

Abstract Aims This study was aimed to investigate the prognostic value of pentraxin-3 in predicting cardiac events in heart failure with reduced left ventricular ejection fraction (HFrEF) patients. Methods and Results A comprehensive search was conducted on Pubmed, Science Direct, Taylor-Francis and LILACS database with the date of publication ranging from inception until 20 July 2021. The identified articles were screened based on pre-specified eligibility criteria which resulted in four prospective cohort studies included in quantitative analysis. Their risk of biases have a mean score of 8.2 ± 0.4 according to the Newcastle-Ottawa Scale, equivalent to good quality rating based on the Agency for Healthcare Research and Quality. In these studies, 3,427 HFrEF patients were enrolled to measure their pentraxin-3 levels on admission and to observe cardiac events, defined as cardiac death or rehospitalization for worsening HF. The association between pentraxin-3 and cardiac events was summarized using forest plot and the heterogeneity was evaluated by I2 index. Higher concentrations of pentraxin-3 on admission were consistently associated with increased cardiac events in HFrEF patients (HR: 1.21, 95% CI: 1.14 - 1.29, I2: 12%). Unfortunately, most of the studies were conducted in Asia and had small sample sizes, which affects the external validity of this meta-analysis. Conclusion Elevated concentrations of pentraxin-3 on admission are associated with cardiac events in HFrEF patients. Further investigations with an emphasis on multi-centre studies, as well as the establishment of the standard cut-off value, are needed.

Abstract 10447: Prognostic Significance of Circulating Monocyte Counts in Patients with Chronic Heart Failure

Introduction: We previously reported that a high monocyte count was an independent and incremental of cardiovascular events in patients with coronary artery disease. To elucidate the prognostic value of monocyte in heart failure (HF), we investigated the association of monocyte counts in patients with HF with their future cardiovascular events. Methods: Consecutive HF patients referred for hospitalization at Kumamoto University Hospital between 2006 and 2013 were registered. We further divided HF patients into two types according to left ventricular ejection fraction (LVEF) (HF with reduced LVEF (HFrEF) and HF with preserved LVEF (HFpEF)). We defined high monocyte group as monocyte counts≥420/mm 3 in HFrEF patients and as monocyte counts≥308/mm 3 in HFpEF patients. Results: In this study, HFrEF was 200 patients and HFpEF was 478 patients. Kaplan-Meier analysis revealed that HFrEF patients with high monocyte group (≥420/mm 3 ) had a significant higher risk of HF-related events (P=0.001) compared with those with low monocyte groups (&lt;420/mm 3 ). By contrast, high and low monocyte groups in HFpEF patients had no significant difference in HF-related events. Multivariate Cox hazard analysis identified a high monocyte count as an independent and significant predictor of future HF-related events in HFrEF patients (hazard ratio:2.24, 95% confidence interval: 1.01-4.99, P=0.04). Conclusions: A high monocyte count was an independent and incremental predictor of HF-related events in HFrEF, but not in HFpEF patients.

Abstract 11485: Left Ventricular Dimensions and Cardiovascular Outcomes in Systolic Heart Failure: The WARCEF Trial

Introduction: There is limited information on the association between left ventricular (LV) dimensions and cardiovascular (CV) outcomes in patients with heart failure with reduced LV ejection fraction (HFrEF) receiving recommended HF treatment. We investigated the association between LV dimensions and CV outcomes in HFrEF patients receiving recommended HF treatment. Methods: We investigated the association between LV echocardiographic dimensions and CV outcomes using conventional Cox models in 1138 HFrEF patients in sinus rhythm randomized to warfarin or aspirin treatment in the WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) trial. Results: LV enlargement, whether by diameter (LV end-diastolic diameter index: LVEDDI, and LV end-systolic diameter index: LVESDI) or volume (LV end-diastolic volume index: LVEDVI, and LV end-systolic volume index: LVESVI), was independently associated with all-cause death [LVEDDI: hazard ratio (HR) per cm/m 2 1.53, LVESDI: HR per cm/m 2 1.65, LVEDVI: HR per 10 ml/m 2 1.07 and LVESVI: HR per 10 ml/m 2 1.10; all p-values &lt; 0.001], CV death (HR 1.68, 1.79, 1.09 and 1.12, respectively; all p-values &lt; 0.001) and HF hospitalization (HR 1.59, 1.79, 1.06 and 1.08, respectively; all p-values &lt; 0.001). No association was observed with myocardial infarction or stroke. The associations were independent of LV ejection fraction values, and incremental to them. LV volumes conferred additional predictive value over LV diameters. Conclusions: LV enlargement is an independent predictor of CV events in patients with HFrEF and recommended HF treatment. LV dimensions should be considered in the risk assessment.

Left ventricular dimensions and cardiovascular outcomes in systolic heart failure: the WARCEF trial.

AimsThere is limited information on the association between left ventricular (LV) dimensions and cardiovascular (CV) outcomes in patients with heart failure (HF) with reduced LV ejection fraction (HFrEF) receiving recommended HF treatment. We investigated the association between LV dimensions and CV outcomes in HFrEF patients receiving recommended HF treatment.Methods and resultsWe investigated the association between LV echocardiographic dimensions and CV outcomes using conventional Cox models in 1138 HFrEF patients in sinus rhythm randomized to warfarin or aspirin treatment in the Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. LV enlargement, whether by diameter [LV end‐diastolic diameter index (LVEDDI) and LV end‐systolic diameter index (LVESDI)] or volume [LV end‐diastolic volume index (LVEDVI) and LV end‐systolic volume index (LVESVI)], was independently associated with all‐cause death [LVEDDI: hazard ratio (HR) per cm/m2 1.53, LVESDI: HR per cm/m2 1.65, LVEDVI: HR per 10 mL/m2 1.07, and LVESVI: HR per 10 mL/m2 1.10; all P values < 0.001], CV death (HR 1.68, 1.79, 1.09, and 1.12, respectively; all P values < 0.001), and HF hospitalization (HR 1.59, 1.79, 1.06, and 1.08, respectively; all P values < 0.001). No association was observed with myocardial infarction or stroke. The associations were independent of LV ejection fraction values, and incremental to them. LV volumes conferred additional predictive value over LV diameters.ConclusionsLeft ventricular enlargement is an independent predictor of CV events in patients with HFrEF and recommended HF treatment. LV dimensions should be considered in the risk assessment.

Right ventricular myocardial work: proof-of-concept for non-invasive assessment of right ventricular function.

Right ventricular myocardial work (RVMW) is a novel method for non-invasive assessment of right ventricular (RV) function utilizing RV pressure-strain loops. This study aimed to explore the relationship between RVMW and invasive indices of right heart catheterization (RHC) in a cohort of patients with heart failure with reduced left ventricular ejection fraction (HFrEF), and to compare values of RVMW with those of a group of patients without cardiovascular disease. Non-invasive analysis of RVMW was performed in 22 HFrEF patients [median age 63 (59-67) years] who underwent echocardiography and invasive RHC within 48 h. Conventional RV functional measurements, RV global constructive work (RVGCW), RV global work index (RVGWI), RV global wasted work (RVGWW), and RV global work efficiency (RVGWE) were analysed and compared with invasively measured stroke volume and stroke volume index. Non-invasive analysis of RVMW was also performed in 22 patients without cardiovascular disease to allow for comparison between groups. None of the conventional echocardiographic parameters of RV systolic function were significantly correlated with stroke volume or stroke volume index. In contrast, one of the novel indices derived non-invasively by pressure-strain loops, RVGCW, demonstrated a moderate correlation with invasively measured stroke volume and stroke volume index (r = 0.63, P = 0.002 and r = 0.59, P = 0.004, respectively). RVGWI, RVGCW, and RVGWE were significantly lower in patients with HFrEF compared to a healthy cohort, while values of RVGWW were significantly higher. RVGCW is a novel parameter that provides an integrative analysis of RV systolic function and correlates more closely with invasively measured stroke volume and stroke volume index than other standard echocardiographic parameters.

A novel age-biomarker-clinical history prognostic index for heart failure with reduced left ventricular ejection fraction

PurposeA model for predicting the prognosis of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) is currently not available. This study aimed to develop an age-biomarker-clinical history prognostic index (ABC-PI) and validate it for the assessment of individual prognosis.Patients and methodsA total of 5,974 HFrEF patients were enrolled and 1,529 were included in this study after excluding missing values and loss to follow-up. Variables that significantly contributed to prediction of all-cause mortality were assessed by Cox regression and latent trait analysis (LTA) was used to validate discrimination of variables.ResultsAfter Cox regression, the following seven most significant variables were selected: age, N-terminal pro-B-type natriuretic peptide, renal dysfunction, left ventricular mass index, percutaneous coronary intervention, atrial fibrillation, and New York Heart Association (C-index: 0.801 ± 0.013). After verification by LTA, discrimination of these seven variables was proven. A nomogram was used to form the ABC-PI, and then the total score was set to 100 points. A lower score indicated a higher risk. After verification, the 3-year mortality rate was 34.7% in the high-risk group and only 2.6% in the low-risk group.ConclusionOur novel ABC-PI shows a good performance and does not require re-input in the original model. The ABC-PI can be used to effectively and practically predict the prognosis of HFrEF patients.

P1647Prognostic significance of circulating leukocyte subtype counts in patients with chronic heart failure

Abstract Background Inflammation, characterized by early leukocyte recruitment, is known to be associated with vascular endothelial dysfunction and atherosclerosis. Previous studies have reported that an increased leukocyte count is a risk factor for the progression of atherosclerosis in cardiovascular diseases, and we previously reported that a high monocyte count was an independent and incremental of cardiovascular events in patients with coronary artery disease. Furthermore, previous study also reported that inflammation play a role in the pathophysiology of heart failure (HF), but few studies have evaluated the prognostic role of monocyte in patients with HF. Purpose To elucidate the prognostic value of monocyte in HF, we investigated the association of monocyte counts in patients with HF with their future cardiovascular events, and compared them among new categories of HF in this study. Methods Consecutive HF patients referred for hospitalization at Kumamoto University Hospital between 2006 and 2015 were registered. Finally, a total of 678 HF patients were enrolled in the study, and were followed prospectively until 2016 or until the occurrence of cardiovascular events. We defined high monocyte group as monocyte counts ≥360/mm3 according to previous clinical reports. We further divided HF patients into three types according to left ventricular ejection fraction (LVEF) (HF with reduced LVEF (HFrEF), HF with mid-range LVEF (HFmrEF), and HF with preserved LVEF (HFpEF)). Results In this study, HFrEF was 82 patients, HFmrEF was 118 patients and HFpEF was 478 patients, respectively. The average of total monocyte counts were 397±136 in HFrEF and 375±172 in HFmrEF, and 341±138 in HFpEF patients. Kaplan-Meier analysis revealed that both HFrEF and HFmrEF patients with high monocyte group (≥360 /mm3) had a significant higher risk of HF-related events (P=0.03 and P=0.02, respectively) but not of total cardiovascular events compared with those with low monocyte groups (&lt;360/mm3) (P=0.001). By contrast, high and low monocyte groups in HFpEF patients had no significant difference in both total cardiovascular and HF-related events. Multivariate Cox hazard analysis identified a high monocyte count as an independent and significant predictor of future HF-related events in HFrEF and HFmrEF patients (hazard ratio: 3.02, 95% confidence interval: 1.20–7.59, p=0.018). Next, by whether they had ischemic heart disease (IHD), we divided HFrEF and HFmrEF patients into two groups. Non-ischemic HF group with high monocyte counts had a significant higher risk of HF-related events compared to those with low monocyte counts (P=0.014). By contrast, there was no statistically significant difference of the occurrences of future HF-related events between in ischemic HF group with high and low monocyte counts. Conclusion A high monocyte count was an independent and incremental predictor of HF-related events in HFrEF and HFmrEF especially with IHD, but not in HFpEF patients.

P4510Impact of secondary tricuspid regurgitation on survival in heart failure - insights from COMMIT-HF registry

Abstract Background Functional tricuspid regurgitation (fTR) is common in left sided heart disease, especially in patients with concomitant left-sided valvular diseases and can lead to functional impairment and reduced survival. However, the impact of fTR on survival in chronic heart failure with reduced left ventricular ejection fraction (HFrEF) without severe left valvular diseases (LVD) is not fully established. The aim of the present study was to observe if moderate to severe fTR may influence the survival in patients with HFrEF without severe LVD. Methods We have analyzed a large single-center registry (n=2731) of HFrEF patients treated in a large-volume cardiovascular center between 2009–2015. After exclusion of patients with severe aortic and mitral valve disease we have included 2435 patients with HFrEF (left ventricular ejection fraction (LVEF) ≤35%). Functional moderate to severe tricuspid regurgitation without severe left valvular diseases was present in 465 patients. Twelve -month vital status was available for the whole patient population. Univariate and multivariate Cox proportional hazard regression models were performed to evaluate the relationship between moderate to severe fTR and mortality in the study group. Results Comparison of clinical data of fTR and non-fTR in HFrEF patients revealed some significant differences (age 63.3±12.9 vs 61.3±12.4, p=0.002; female sex 25.8% vs 17,9%, p&lt;0.001; chronic kidney disease stage III-V 45.3 vs 26.6%, p=0.001; atrial fibrillation 52.4% vs 28.5%, p&lt;0.001). Twelve-month all-cause mortality was over 2-fold higher in the fTR group (21.2% vs 8.1%, p&lt;0.001). There were no significant differences with regard to the medical treatment, implantable defibrillator or cardiac resynchronization therapy. The presence of fTR was identified as an independent echocardiographic factor impaired 12-month all-cause survival (HR 1.59, CI 1.2- 2.09, p&lt;0.001, figure 1) Conclusion Apart from the LVEF, the presence of moderate to severe fTR may predict 12-month all-cause mortality in patients with HFrEF. Acknowledgement/Funding None

1384MitraClip treatment of functional mitral regurgitation - A meta-analysis

Abstract Moderate-to-severe or severe functional mitral regurgitation (FMR) is associated with higher rates of hospitalizations and with increased mortality in heart failure with reduced left ventricular ejection fraction (HFrEF). Transcatheter mitral valve repair by MitraClip® implantation (TMVrMC) may effectively reduce severe MR, and is associated with symptomatic improvement. However, the long-term clinical effects of this procedure are not well defined. Aims We analyzed outcomes for rehospitalization and survival in heart failure patients with moderate-to-severe or severe functional mitral regurgitation (FMR) treated by either medical treatment (MT) only TMVrMC+MT by meta-analysis. Methods and results By systematic search of bibliographic databases, we evaluated publications comparing heart failure patients with FMR treated by MT only versus treatment by MT combined with TMVrMC. Studies with a minimum of 25 enrolled patients and a follow/up period of at least 12 months were deemed eligible for this meta-analysis. We identified n=7 studies enrolling 2,884 HFrEF patients, divided into two study arms: TMVrMC+MT (n=1,618), versus FMR patients receiving MT only (n=1,266). At 12 months, there was a significant reduction in all-cause mortality favoring TMVR+MT (OR: 0.67; CI 95% 0.55–0.81), as well as a reduction of unplanned rehospitalizations (OR: 0.69; 95%; CI 0.53–0.89), compared with the MT only patients. At 24 months, there was a significant reduction of all-cause mortality in the TMVrMC+MT patient group (OR: 0.50; CI: 95%: 0.38–0.66; p&lt;0.001). TMVrMC+MT was associated with significantly lower rates of unplanned re-admissions for heart failure compared with MT only at 12 months (OR: 0.69; 95% CI: 0.53–0.89; p&lt;0.001) and at 24 months (OR: 0.53; 95% CI: 0.39–0.71; p&lt;0.001). In one publication, a survival benefit of TMVrMC+MT over MT alone was shown at 5 years post intervention (HR: 0.75; 95% CI: 0.69–0.94; p=0.012) after weighting for propensity score and controlling for age. Conclusions This meta-analysis on n=2,884 patients with moderate-to-severe or severe FMR reveals that TMVrMC+MT, as compared with MT alone, is associated with a significant reduction of rehospitalizations and improvement of survival. These data imply additional evidence for TMVrMC in eligible heart failure patients with relevant FMR, which might be important for an update of the corresponding guidelines.

Exercise-based cardiac rehabilitation in patients with reduced left ventricular ejection fraction: The Cardiac Rehabilitation Outcome Study in Heart Failure (CROS-HF): A systematic review and meta-analysis.

BackgroundIn heart failure with reduced left ventricular ejection fraction (HFrEF) patients the effects of exercise-based cardiac rehabilitation on top of state-of-the-art pharmacological and device therapy on mortality, hospitalization, exercise capacity and quality-of-life are not well established.DesignThe design of this study involved a structured review and meta-analysis.MethodsEvaluation of randomised controlled trials of exercise-based cardiac rehabilitation in HFrEF-patients with left ventricular ejection fraction ≤40% of any aetiology with a follow-up of ≥6 months published in 1999 or later.ResultsOut of 12,229 abstracts, 25 randomised controlled trials including 4481 HFrEF-patients were included in the final evaluation. Heterogeneity in study population, study design and exercise-based cardiac rehabilitation-intervention was evident. No significant difference in the effect of exercise-based cardiac rehabilitation on mortality compared to control-group was found (hazard ratio 0.75, 95% confidence interval 0.39–1.41, four studies; 12-months follow-up: relative risk 1.29, 95% confidence interval 0.66–2.49, eight studies; six-months follow-up: relative risk 0.91, 95% confidence interval 0.26–3.16, seven studies). In addition there was no significant difference between the groups with respect to ‘hospitalization-for-any-reason’ (12-months follow-up: relative risk 0.79, 95% confidence interval 0.41–1.53, four studies), or ‘hospitalization-due-to-heart-failure’ (12-months follow-up: relative risk 0.59, 95% confidence interval 0.12–2.91, four studies; six-months follow-up: relative risk 0.84, 95% confidence interval 0.07–9.71, three studies). All studies show improvement of exercise capacity. Participation in exercise-based cardiac rehabilitation significantly improved quality-of-life as evaluated with the Kansas City Cardiomyopathy Questionnaire: (six-months follow-up: mean difference 1.94, 95% confidence interval 0.35–3.56, two studies), but no significant results emerged for quality-of-life measured by the Minnesota Living with Heart Failure Questionnaire (nine-months or more follow-up: mean difference –4.19, 95% confidence interval –10.51–2.12, seven studies; six-months follow-up: mean difference –5.97, 95% confidence interval –16.17–4.23, four studies).ConclusionNo association between exercise-based cardiac rehabilitation and mortality or hospitalisation could be observed in HFrEF patients but exercise-based cardiac rehabilitation is likely to improve exercise capacity and quality of life.

Comparable prognostic impact of BNP levels among HFpEF, Borderline HFpEF and HFrEF: a report from the CHART-2 Study.

We aimed to compare the usefulness of plasma levels of B-type natriuretic peptide (BNP) for long-term risk stratification among patients with heart failure (HF) with preserved left ventricular ejection fraction (LVEF) (HFpEF), borderline HFpEF, and HF with reduced LVEF (HFrEF) in the same HF cohort. In the CHART-2 Study (N = 10,219), we categorized 4301 consecutive Stage C/D HF patients (mean age 68.7years, female 32.4%) into 3 groups: HFpEF (LVEF ≥ 50%, N = 2893), borderline HFpEF (LVEF 40-50%, N = 666), and HFrEF (LVEF ≤ 40%, N = 742). During the median 6.3-year follow-up, all-cause deaths occurred in 887 HFpEF, 330 borderline HFpEF, and 330 HFrEF patients. Although median BNP levels increased from HFpEF, borderline HFpEF to HFrEF (85.3, 126 and 208pg/ml, respectively, P < 0.001), the relationship between log2 BNP levels and the mortality risk was comparable among the 3 groups. As compared with patients with BNP < 30pg/ml, those with 30-99, 100-299 and ≥ 300pg/ml had comparably increasing mortality risk among the 3 groups (hazard ratio 2.5, 4.7 and 7.8 in HFpEF, 2.1, 4.2 and 7.0 in borderline HFpEF, and 3.0, 4.7 and 9.5 in HFrEF, respectively, all P < 0.001). BNP levels have comparable prognostic impact among HFpEF, borderline HFpEF, and HFrEF patients.

In HFREF patients, sacubitril/valsartan, given at relatively low doses, does not lead to increased mortality or hospitalization : Aretrospective cohort study.

In heart failure with reduced left ventricular ejection fraction (HFREF) patients, the dosage of sacubitril/valsartan is modulated according to agradual increase regimen. Nevertheless, if patients exhibit tolerability problems, aprovisional reduction of the dose of sacubitril/valsartan or even its interruption are recommended. This study provides estimates of respective proportions of patients receiving minimum or intermediate doses of sacubitril/valsartan. In addition, acomparison was made to detect possible differences regarding all-cause mortality and heart failure hospitalization in patients treated with the recommended optimum dose compared to those receiving submaximum maintenance doses of sacubitril/valsartan. Patients treated with sacubitril/valsartan in addition to beta-blocker and mineralocorticoid receptor blocker were68. Among them, 20patients (29.4%), were identified as having clinical features that were contraindications to the administration of sacubitril/valsartan at full dose. The subsequent decision was to maintain an intermediate dose in 11patients and to reduce the dose to the minimum level allowed, i.e., 24 mg/26 mg twice daily in nine patients. After a median follow-up of 5.25months, no differences were found concerning the risk of all-cause death by comparing patients treated with reduced versus those subjected to target doses of sacubitril/valsartan (odds ratio [OR] = 1.666; 95% confidence interval [CI] = 0.256-10.823; p = 0.6266). Patients taking reduced doses had a similar risk of heart failure hospitalizations when compared to patients treated with the target dose (OR = 0.789; 95% CI: 0.077-8.0808; p = 1.00). During amedian follow-up of 5.25months, in the group of patients who had proven to be intolerant to the maximum dose of sacubitril/valsartan, use of reduced doses of the drug did not result in increased all-cause mortality or heart failure hospitalization compared to patients treated with sacubitril/valsartan at the target dose.

Differential efficacy profile of aldosterone receptor antagonists, depending on the type of chronic heart failure, whether with reduced or preserved left ventricular ejection fraction-results of a meta-analysis of randomized controlled trials.

Because of renin-angiotensin-aldosterone system (RAAS) activation, the patients with chronic heart failure (CHF) manifest increased ventricular stress, with impaired left ventricular function, and a slowing down in systemic venous drainage. More importantly, a reduction of the patient's life expectancy has been proven in the case of RAAS overstimulation. For these reasons, huge efforts have been made to obtain molecules able to efficaciously antagonize the RAAS overstimulation, such as aldosterone receptor antagonists (ARAs). These drugs have been shown to improve clinical outcomes in patients with heart failure with reduced left ventricular ejection fraction (HFREF), but not in those with preserved left ventricular ejection fraction (HFpEF). In order to study this topic more deeply, we carried out a meta-analysis of selective and nonselective ARAs in HFREF and HFpEF. Only randomized controlled trials (RCTs) were incorporated in our meta-analysis. Studies were included if they satisfied the following criteria: experimental groups included patients with CHF treated with ARAs in addition to the conventional therapy; control groups included patients with CHF receiving conventional therapy without ARAs. Outcomes of interest were all-cause mortality, cardiovascular hospitalizations, hyperkalemia, or gynecomastia. Overall, 15 RCTs including a total of 15,671 patients were eligible for inclusion in the meta-analysis. ARA use in patients with heart failure was associated with a significant reduction in adverse outcomes. Indeed, a significant reduced odds of all-cause death among CHF patients treated with ARAs compared to controls was found [odds ratio (OR) =0.79; 95% CI: 0.73-0.87]. Subgroup analysis based on the heart failure (HF) type revealed a statistically significant benefit as regards all- cause death for patients with HFREF (OR =0.77; 95% confidence interval (CI): 0.69-0.84), but not for those with HFpEF (OR =0.91; 95% CI: 0.76-1.1). Furthermore reduced odds of CV hospitalizations was detected in the entire group of CHF patients under treatment with ARAs (OR =0.73; 95% CI: 0.61-0.89) as well as among HFREF patients treated with ARAs, compared to controls (OR =0.66; 95% CI: 0.51-0.85). Hyperkalemia was significantly more frequent with ARA use. Besides, ARA use was shown to be associated with the occurrence of gynecomastia. In particular, selective ARAs didn't induce significant amounts of gynecomastia compared to controls (OR =0.74; 95% CI: 0.43-1.27), while nonselective ARAs did (OR =8.22; 95% CI: 4.9-13.81). Based on this meta-analysis, ARAs should be systematically used in patients with HFREF, in whom these drugs proved to reduce all-cause mortality and hospitalizations from cardiac cause. Conversely, ARA usage in HFpEF patients is questionable since in this CHF setting no significant improvement in clinical endpoints has been demonstrated so far. New selective ARAs are devoid of the risk of gynecomastia, while are similar to nonselective ARAs with regard to the efficacy profile as well as to the risk of eliciting hyperkalemia.

Characterization of heart failure patients with mid-range left ventricular ejection fraction-a report from the CHART-2 Study.

The new category of heart failure (HF), HF with mid-range left ventricular ejection fraction (LVEF) (HFmrEF), has recently been proposed. However, the clinical features of HFmrEF, with reference to HF with preserved LVEF (HFpEF) and HF with reduced LVEF (HFrEF) in the same HF cohort, remain to be fully examined. In the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 Study, we examined 3480 consecutive HF patients with echocardiography data consisting of 2154 HFpEF (LVEF ≥50%), 596 HFmrEF (LVEF 40-49%) and 730 HFrEF (LVEF <40%). While clinical characteristics and prognostic factors of HFmrEF were intermediate between HFpEF and HFrEF, prognosis of HFmrEF resembled HFpEF and the prognostic impact of cardiovascular medications in HFmrEF resembled that of HFrEF. Analysis of LVEF transition among the three groups revealed that HFmrEF and HFrEF dynamically transitioned to other categories, especially within 1 year, whereas HFpEF did not; HFmrEF at registration transitioned to HFpEF and HFrEF by 44% and 16% at 1 year, and 45% and 21% at 3 years, respectively. Landmark analysis demonstrated that, regardless of HF stages at registration, HFmrEF patients at 1 year had mortality comparable to that of HFpEF patients, which was better than HFrEF patients, but HFmrEF patients at registration had increased mortality when transitioned to HFrEF at 1 year. These results indicate that clinical characteristics of HFmrEF are intermediate between HFpEF and HFrEF and that HFmrEF dynamically transitions to HFpEF or HFrEF, especially within 1 year, suggesting that HFmrEF represents a transitional status or an overlap zone between HFpEF and HFrEF, rather than an independent entity of HF.

Abstract 13999: Elevated Asleep Blood Pressure is Associated With All-cause and Cardiovascular Mortality in Heart Failure With Preserved Left Ventricular Ejection Fraction (HFpEF) -From Nara-HF Study

Introduction: Abnormal circadian blood pressure (BP) rhythms are one of the risks of cardiovascular diseases and death. However, circadian BP rhythms in heart failure (HF) patients are unclear. Therefore, we examined the relationship between circadian BP rhythms for survival in HF patient. Moreover, we valued the difference of circadian BP rhythms between HF with preserved left ventricular ejection fraction (HFpEF) and HF with reduced left ventricular ejection fraction (HFrEF). Methods: Of 810 consecutive patients with acute decompensated HF emergently admitted to our hospital, we studied 228 HF patients performed ambulatory blood pressure monitoring (ABPM) at discharge. We examined the relationship between circadian BP rhythms and survival in HFpEF and HFrEF. Kaplan-Meier survival analysis and Cox proportional hazard model were performed to assess outcomes. Results: During a mean follow-up of 27.9 months, there were 80 deaths from all causes, including 36 deaths from cardiovascular causes. The pattern of circadian BP rhythms was similar between HFpEF and HFrEF. In HFpEF patients, Kaplan-Meier analysis showed that all-cause and cardiovascular death were significantly higher in patients with the pattern of elevated asleep BP (EABP), in which sleep BP exceeded awake BP (log-rank P=0.0298 and P=0.0195, respectively). In a multivariate analysis, EABP pattern was an independent predictor for all-cause and cardiovascular death (HR 2.57; 95% CI 1.09-6.13; P=0.0310 and HR 10.66; 95% CI 1.91-93.9; P=0.0063, respectively) after adjusted by age, hemoglobin and brain natriuretic peptide. However, these findings were not observed in HFrEF. Conclusions: EABP pattern was associated with increasing risk for adverse outcome in HFpEF patients, but not in HFrEF patients. Although further studies are necessary to elucidate the mechanism, we should pay attention to EABP pattern in HFpEF.