Mid-range Left Ventricular Ejection Fraction Research Articles

Decompensation of Heart Failure in "Fragile" Patients: Clinical Features and Approaches to Therapy

To evaluate the impact of frailty syndrome (FS) on the course of acute decompensated heart failure (ADHF) and the quality of drug therapy before discharge from the hospital in patients with reduced and moderately reduced left ventricular ejection fraction (LVEF). This open prospective study included 101 patients older than 75 years with reduced and mid-range LVEF hospitalized for decompensated chronic heart failure (CHF). FS was detected during the outpatient follow-up and identified using the Age is Not a Hindrance questionnaire, the chair rise test, and the One Leg Test. The "fragile" group consisted of 54 patients and the group without FS included 47 patients. Clinical characteristics of patients were compared, and the prescribing rate of the main drugs for the treatment of CHF was assessed upon admission to the hospital. The sacubitril/valsartan or dapagliflozin therapy was initiated in the hospital; prescribing rate of the quadruple therapy was assessed upon discharge from the hospital. Patients with reduced LVEF were followed up for 30 days, and LVEF was re-evaluated to reveal possible improvement due to optimization of therapy during hospitalization. Statistical analysis was performed with the SPSS 23.0 software. The main causes for decompensation did not differ in patients of the compared groups. According to the correlation analysis, FS was associated with anemia (r=0.154; p=0.035), heart rate ≥90 bpm (r=0.185; p=0.020), shortness of breath at rest (r =0.224; p=0.002), moist rales in the lungs (r=0.153; p=0.036), ascites (r=0.223; p=0.002), increased levels of the N-terminal pro-brain natriuretic peptide (NT-proBNP) (r= 0.316; p<0.001), hemoglobin concentration <120 g / l (r=0.183; p=0.012), and total protein <65 g / l (r=0.153; p=0.035) as measured by lab blood tests. Among patients with LVEF ≤40 % in the FS group (n=33) and without FS (n=33), the quadruple therapy was a part of the treatment regimen at discharge from the hospital in 27.3 and 3.0 % of patients, respectively (p=0.006). According to the 30-day follow-up data, improvement of LVEF was detected in 18.2% of patients with LVEF ≤40% in the FS group and 12.1% of patients with LVEF ≤40% in the FS-free group (p=0.020). In patients with LVEF 41-49 % in the FS (n=21) and FS-free (n=14) groups, the prescribing rate of the optimal therapy, including sacubitril/valsartan, sodium-glucose cotransporter 2 inhibitors, beta-blockers, and mineralocorticoid receptor antagonists, no statistically significant differences were detected (14.3 and 7.1 %, respectively; p=0.515) at discharge from the hospital. Patients with ADHF and FS showed more pronounced clinical manifestations of decompensation, anemia, heart rate ≥90 beats/min, and higher levels of NT-proBNP upon admission. The inpatient therapy with sacubitril/valsartan or dapagliflozin was more intensively initiated in FS patients with reduced LVEF. An individualized approach contributed to achieving a prescribing rate of sacubitril/valsartan of 39.4%, dapagliflozin of 39.4%, and quadruple therapy of 27.3% upon discharge from the hospital.

The Effect of Beta-Blocker Post-Myocardial Infarction With Ejection Fraction >40% Pooled Analysis From Seven Arabian Gulf Acute Coronary Syndrome Registries.

The use of beta-blockers (BB) in reduced left ventricular ejection fraction (LVEF) post-myocardial infarction (MI) is associated with reduced 1-year mortality, while their role in patients with mid-range and preserved LVEF post-MI remains controversial. We studied 31,620 patients who presented with acute coronary syndrome (ACS) enrolled in seven Arabian Gulf registries between 2005 and 2017. Patients with LVEF ≤40% were excluded. The remaining cohort was divided into two groups: BB group (n = 15,541) and non-BB group (n = 2,798), based on discharge medications. Patients in the non-BB group were relatively younger (55.3 vs. 57.4, P = .004) but higher risk at presentation; with higher Global Registry of Acute Coronary Events (GRACE) score (119.2 vs 109.2, P < .001), higher percentage of cardiogenic shock (3.5 vs 1.4%, P < .001), despite lower prevalence of comorbidities, such as hypertension and hyperlipidemia. BB use was associated with lower 1-year mortality in a multivariate logistic regression analysis, adjusting for major confounders [adjusted odds ratio (OR): 0.71 (95% CI 0.51-0.99)]. This remained the case in a sensitivity analysis using propensity score matching [adjusted OR: 0.34 (95% CI 0.16-0.73)]. In this study, using Arabian Gulf countries registries, the use of BB after ACS with LVEF >40% was independently associated with lower 1-year mortality.

The Clinical Evolution of Diffuse Myocardial Fibrosis in Patients With Arterial Hypertension and Heart Failure With Mildly Reduced Ejection Fraction Treated by Olmesartan or Sacubitril / Valsartan.

Aim A 12-month evaluation of the potentialities of the angiotensin II receptor inhibitor olmesartan (Olme) and the angiotensin receptor and neprilysin inhibitor (ARNI) sacubitril/valsartan in patients with arterial hypertension (AH) and dyslipidemia in the dynamics of the following indicators of chronic heart failure (CHF): N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), LV global longitudinal strain (LV GLS) in diffuse myocardial fibrosis (MF) previously diagnosed by magnetic resonance imaging (MRI).Material and methods Olmesartan medoxomil (n=56) and sacubitril/valsartan (n=63) were used for 12 months in patients with hypertension, dyslipidemia and NYHA functional class II-III CHF with mid-range LVEF (CHFmrEF). MF was diagnosed by the following MRI criteria: late gadolinium enhancement and an increased proportion of extracellular matrix (33% or more). The frequency of persisting late gadolinium enhancement and the increased proportion of extracellular matrix (33% or more) was evaluated at 12 months; changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), NT-proBNP, and LV GLS were evaluated after 3, 6, and 12 months of follow-up.Results Baseline parameters did not differ between groups. The late gadolinium enhancement and increased proportion of extracellular matrix were present at baseline in all patients of both groups (100%; p=1.0). Already at 3 months, statistically significant decreases in SBP and DBP were observed in both groups. In addition, the LV GLS monitoring showed LV GLS significantly increased in both groups after 3 months and continued changing after 6 and 12 months. The NT-proBNP concentration significantly decreased in both groups already after 3 months and continued to decrease after 6 and 12 months. At 6 and 12 months, sacubitril/valsartan was superior to olmesartan in reducing SBP and NT-proBNP and in restoring LV GLS. At 12 months, the incidence of persisting, abnormal late gadolinium enhancement and increased proportion of extracellular matrix was significantly less in the ARNI group.Conclusion Olmesartan was demonstrated effective in the multi-modality therapy of CHFmrEF and MF in patients with AH and dyslipidemia. ARNI was superior to olmesartan in this regard, but further research of this issue is required.

Study of the clinical and epidemiological profile of heart failure

The purpose was to describe the clinical and epidemiological profile of patients with Heart Failure (HF) treated at a specialized clinic in the Unified Health System. This is a descriptive, individual and cross-sectional study, which collected data from medical records of patients with HF. Patients were divided into three groups according to the stroke volume: preserved, mid-range and reduced. A total of 545 medical records were evaluated, with a mean age of 64.9 ± 13.6 years, and 55.6% of which were male. Hypertension (76.7%), coronary artery disease (38.5%), and diabetes mellitus (37.2%) were the main risk factors. Myocardial ischemia was the main etiology (36.40%), followed by Chagas disease (20.22%). The valve etiology was frequently associated with reduced LVEF (left ventricular ejection fraction) (Pearson's ρ &lt;0.06), with mid-range LVEF (Pearson's ρ &lt;0.10) and with preserved LVEF (Pearson's ρ &lt;0.39). The ischemic etiology was frequent in preserved LVEF (Pearson's ρ &lt;0.08). The findings showed a strong association between valve disease and preserved LVEF; frequent association between mid-range LVEF and valve and ischemic disease; frequent association between valve disease and reduced LVEF.

FACE study: 2-year follow-up of adaptive servo-ventilation for sleep-disordered breathing in a chronic heart failure cohort

BackgroundSleep-disordered breathing (SDB) is a common comorbidity in patients with heart failure (HF) and is associated with worse prognosis. ObjectivesThis study evaluated the effects of adaptive servo-ventilation (ASV) on morbidity and mortality in a large heterogeneous population of HF patients with different etiologies/phenotypes. MethodsConsecutive HF patients with predominant central sleep apnea (± obstructive sleep apnea) indicated for ASV were included; the control group included patients who refused or stopped ASV before three months follow-up. Six homogenous clusters were determined using the latent class analysis (LCA) method. The primary endpoint was time to composite first event (all-cause death, lifesaving cardiovascular intervention, or unplanned hospitalization for worsening of chronic HF). ResultsOf 503 patients at baseline, 324 underwent 2-year follow-up. Compared to control group, 2-year primary endpoint event-free survival was significantly greater in patients in ASV group only in univariable analysis (1.67, 95% [1.12–2.49]; p = 0.01). Secondary endpoints, event-free of cardiovascular death or heart failure-related hospitalization and all-cause death or all-cause hospitalization were positively impacted by ASV (univariate and multivariable analysis). LCA identified two groups, with preserved and mid-range left ventricular ejection fraction (LVEF) and severe hypoxia, in whom ASV increase prognosis benefit. ConclusionsPatients with HF and SDB are a highly heterogeneous group identified using LCA. Systematic deep phenotyping is essential to ensure that ASV is prescribed to those benefit from therapy, as ASV use in patients with severe hypoxic burden and those with HFpEF was associated with a significant reduction in cardiovascular events and mortality. Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT01831128.

No-Implant Interatrial Shunt for HFpEF: 6-Month Outcomes From Multicenter Pilot Feasibility Studies

BackgroundMost approaches to the creation of an interatrial shunt require placement of a permanent implant to maintain patency. ObjectivesThe goal of this study was to investigate the safety and efficacy of a no-implant interatrial shunt for patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF). MethodsThis was a multicenter, uncontrolled study of patients with HFpEF/HFmrEF and NYHA functional class ≥II, ejection fraction >40%, and pulmonary capillary wedge pressure (PCWP) during supine exercise ≥25 mm Hg with PCWP-to–right atrial gradient ≥5 mm Hg. Follow-up was through 6 months with imaging to assess shunt durability. ResultsA total of 28 patients were enrolled: mean age was 68 ± 9 years, and 68% were female. Baseline resting and peak exercise PCWP were 19 ± 7 mm Hg and 40 ± 11 mm Hg, respectively. All procedures displayed technical success with confirmation of left-to-right flow (shunt diameter 7.1 ± 0.9 mm). At 1 month, peak exercise PCWP decreased 5.4 ± 9.6 mm Hg (P = 0.011) with no change in right atrial pressure. There were no serious device or procedure-related adverse events through 6 months. Mean 6-minute walk distance increased 101 ± 71 meters (P < 0.001); Kansas City Cardiomyopathy Questionnaire Overall Summary Score increased 26 ± 19 points (P < 0.001); N-terminal pro–B-type natriuretic peptide decreased 372 ± 857 pg/mL (P = 0.018); and shunt patency was confirmed with unchanged diameter. ConclusionsIn these feasibility studies of a no-implant interatrial shunt, HFpEF/HFmrEF shunts exhibited stability with favorable safety and early efficacy signals. The results show promise toward this new approach for treating patients with HFpEF/HFmrEF and an appropriate hemodynamic profile. (Evaluation of the Safety and Feasibility of a Percutaneously Created Interatrial Shunt to Alleviate Heart Failure Symptoms in Patients With Chronic Heart Failure and Preserved or Mid-Range Left Ventricular Ejection Fraction [ALLEVIATE-HF-1]; NCT04583527; Evaluation of the Safety and Effectiveness of a Percutaneously Created Interatrial Shunt to Alleviate Heart Failure Symptoms in Patients With Chronic Heart Failure and Preserved or Mid-Range Left Ventricular Ejection Fraction [ALLEVIATE-HF-2]; NCT04838353)

Left ventricular isovolumetric relaxation time is a potentially new marker of short-term and long-term prognosis in patients with acute heart failure’s decompensation and mid-range ejection fraction

Purpose: to assess the role of left ventricular (LV) isovolumic relaxation time (IVRT) as a predictor of adverse outcome in acute decompensated heart failure (ADHF) against the background of intermediate ejection fraction (EF) of the left ventricle.Materials and methods. The study included 121 patients aged 37 to 85 years (mean age 67.2±2.5 years) with ADHF against the background of LV ЕF; 78 — male, 43 are fermale. In all patients, the time between the end of blood flow in the outflow tract and the beginning of blood flow in the inflow tract was determined, i.e., LV IVRT. According to this parameter, the whole group was divided into 3 samples: with an average LV IVRT (70–100 ms — 54 patients), increased (more than 100 ms — 15 patients) — or reduced LV IVRT (less than 70 ms — 52 patients).Results. The mean LV IVRT in group 1 was 87.5±6.4 ms, in group 2–106.4±9.7 ms, in group 3–55.3±4.1 ms. Hospital mortality (HM) in the entire sample was 5.3%, long-term (24 months) (LM) — 39.6%. The obtained results were subjected to correlation analysis: HM was characterized by a connection with LV IVRT (r= –0.295, p&lt;0.05), but the dependence was inversely proportional. For LM, the correlation coefficient with LV IVRT was 0.519, p&gt;&lt;0.05, which is typical for an average connection strength. Conclusions: 1. The value of IVRT in patients with midrange LV EF correlated negatively with the levels of both in-hospital and long-term mortality: low numbers of IVRT statistically significantly predicted an increase in mortality from all causes, while a decrease in mortality was observed at high values of IVRT. 2. In patients who are hospitalized for ADHF against the background of mid-range LV EF, it is advisable to determine the LV IVRT to assess the immediate and long-term prognosis of the disease. Keywords: heart failure, acute decompensation, time of isovolumetric relaxation of the left ventricle, prognosis&gt; ˂ 0.05), but the dependence was inversely proportional. For LM, the correlation coefficient with LV IVRT was 0.519, p ˂ 0.05, which is typical for an average connection strength.Conclusions: 1. The value of IVRT in patients with midrange LV EF correlated negatively with the levels of both in-hospital and long-term mortality: low numbers of IVRT statistically significantly predicted an increase in mortality from all causes, while a decrease in mortality was observed at high values of IVRT. 2. In patients who are hospitalized for ADHF against the background of mid-range LV EF, it is advisable to determine the LV IVRT to assess the immediate and long-term prognosis of the disease.

Prediction of Sudden Cardiac Death Manifesting With Documented Ventricular Fibrillation or Pulseless Ventricular Tachycardia.

This study aimed to develop a novel clinical prediction algorithm for avertable sudden cardiac death. Sudden cardiac death manifests as ventricular fibrillation (VF)/ ventricular tachycardia (VT) potentially treatable with defibrillation, or nonshockable rhythms (pulseless electrical activity/asystole) with low likelihood of survival. There are no available clinical risk scores for targeted prediction of VF/VT. Subjects with out-of-hospital sudden cardiac arrest presenting with documented VF or pulseless VT (33% of total cases) were ascertained prospectively from the Portland, Oregon, metro area with population ≈1 million residents (n=1,374, 2002-2019). Comparisons of lifetime clinical records were conducted with a control group (n=1,600) with ≈70% coronary disease prevalence. Prediction models were constructed from a training dataset using backwards stepwise logistic regression and applied to an internal validation dataset. Receiver operating characteristic curves (Cstatistic) were used to evaluate model discrimination. External validation was performed in a separate, geographically distinct population (Ventura County, California, population ≈850,000, 2015-2020). A clinical algorithm (VFRisk) constructed with 13 clinical, electrocardiogram, and echocardiographic variableshad very good discrimination in the training dataset (C statistic=0.808; [95% CI: 0.774-0.842]) and was successfully validated in internal (C statistic=0.776 [95% CI: 0.725-0.827]) and external (C statistic=0.782 [95% CI: 0.718-0.846]) datasets. The algorithm substantially outperformed the left ventricular ejection fraction (LVEF)≤35% (Cstatistic=0.638) and performed well across the LVEF spectrum. An algorithm for prediction of sudden cardiac arrest manifesting with VF/VT was successfully constructed using widely available clinical and noninvasive markers. These findings have potential to enhance primaryprevention, especially in patients with mid-range or preserved LVEF.

Possible pathway for heart failure with preserved ejection fraction prevention and treatment: the angiotensin-converting enzyme inhibitor effect on endothelial function in comorbid patients.

Aim To evaluate the effect of perindopril on the endothelial function and levels of endothelial dysfunction markers in groups of patients with heart failure with preserved (HFpEF) and mid-range (intermediate) left ventricular ejection fraction (HFmrEF).Material and methods 40 patients with HFpEF (n=20) and HFmrEF (n=20) were evaluated. At baseline, parameters of the morpho-functional state of large blood vessels and of microvessels were evaluated with photoplethysmography, and levels of E-selectin and endothelin-1 (ET-1) were measured. The patients were prescribed perindopril, and after 12 months of treatment, photoplethysmographic parameters and endothelial dysfunction markers were determined again.Results After 12 months of the perindopril treatment, improvements in the endothelial function of both large blood vessels and microvessels were noted. The phase shift increased from 10.1 to 10.9 ms in the HFpEF group (р=0.001) and from 8.35 to 9.65 ms in the HFmrEF group (р=0.002). Furthermore, the occlusion index increased from 1.45 to 1.75 in patients with HFpEF (р=0.004) and from 1.5 to 1.75 in patients with HFmrEF (р=0.010). The Е-selectin concentration decreased in both groups, from 57.25 to 42.4 ng/ml (р=0.00008) and from 40.5 to 35.7 ng/ml (р=0.010) in patients with HFpEF and HFmrEF, respectively. The ET-1 concentration decreased from pg/ml (р=0.010) in patients with HFpEF whereas in patients with HFmrEF, there was no significant change in the ET-1 concentration after 12 months of the perindopril treatment.Conclusion At 12 months, the endothelial function improved and E-selectin and ET-1 levels decreased in patients with HFpEF and HFmrEF.

Prognostic impact of high-sensitive troponin on 30-day mortality in patients with acute heart failure and different classes of left ventricular ejection fraction

High-sensitive troponin T (hs-TnT) is increasingly used for prognostication in patients with acute heart failure (AHF). However, uncertainty exists whether hs-TnT shows comparable prognostic performance in patients with heart failure and different classes of left ventricular ejection fraction (LV-EF). The aim of the present study was to assess the prognostic value of hs-TnT for the prediction of 30-day mortality depending on the presence of HF with preserved ejection fraction (HFpEF), HF with mid-range LV-EF (HFmrEF) and HF with reduced LV-EF (HFrEF) in patients with acutely decompensated HF. Patients admitted to our institution due to AHF were retrospectively included. Clinical information was gathered from electronic and paper-based patient charts. Patients with myocardial infarction were excluded. A total of 847 patients were enrolled into the present study. A significant association was found between HF groups and hs-TnT (regression coefficient -0.018 for HFpEF vs. HFmrEF/HFrEF; p = 0.02). The area under the curve (AUC) of hs-TnT for the prediction of 30-mortality was significantly lower in patients with HFpEF (AUC 0.61) than those with HFmrEF (AUC 0.80; p = 0.01) and HFrEF (AUC 0.73; p = 0.04). Hs-TnT was not independently associated with 30-day outcome in the HFpEF group (OR 1.48 [95%-CI 0.89–2.46]; p = 0.13) in contrast to the HFmrEF group (OR 4.53 [95%-CI 1.85–11.1]; p < 0.001) and HFrEF group (OR 2.58 [95%-CI 1.57–4.23]; p < 0.001). Prognostic accuracy of hs-TnT in patients hospitalized for AHF regarding 30-day mortality is significantly lower in patients with HFpEF compared to those with HFmrEF and HFrEF.

Incidence, Clinical Characteristics and Short-Term Prognosis in Patients With Cardiogenic Shock and Various Left Ventricular Ejection Fractions After Acute Myocardial Infarction

The 2016 European Society of Cardiology Guidelines introduced a new term, mid-range left ventricular ejection fraction (mrEF) heart failure, however, the clinical characteristics and short-term outcomes in cardiogenic shock patients with mrEF after acute myocardial infarction remain unclear. This retrospective study analyzed the baseline characteristics, management, and outcomes according to the left ventricular ejection fraction (LVEF), reduced LVEF (rEF) ≤40%, mrEF 41% to 49%, and preserved LVEF (pEF) ≥50% in patients with acute myocardial infarction complicated by cardiogenic shock. The primary end point was 30-day all-cause mortality and the secondary end point was the composite events of major adverse cardiovascular events (MACEs). In 218 patients, 71 (32.6%) were patients with mrEF. Compared with those with pEF, patients with mrEF had some similar clinical characteristics to that of rEF. The 30-day all-cause mortality in patients with rEF, mrEF, and pEF were 72.7%, 56.3%, and 32.0%, respectively (p = 0.001). The 30-day MACE were 90.9%, 69.0%, and 60.2%, respectively (p = 0.001). After multivariable adjustment, patients with mrEF and rEF had comparable 30-day all-cause mortality (hazard ratio [HR] = 0.81, 95% confidence interval [CI] 0.50 to 1.33, p = 0.404), and pEF was associated with decreased risk of 30-day all-cause mortality compared with rEF (HR = 0.41, 95% CI 0.24 to 0.71, p = 0.001). In contrast, the risk of 30-day MACE in mrEF and pEF were lower than that of rEF (HR = 0.62, 95% CI 0.40 to 0.96, p = 0.031 and HR = 0.53, 95% CI 0.34 to 0.80, p = 0.003, respectively). In conclusion, 1/3 of patients with acute myocardial infarction complicated by cardiogenic shock were mrEF. The clinical characteristics and short-term mortality in patients with mrEF were inclined to that of rEF and the occurrence of early left ventricular systolic dysfunction is of prognostic significance.

Impact of left ventricular ejection fraction on clinical outcomes in females undergoing percutaneous coronary intervention with drug-eluting stents

Abstract Background Reduced left ventricular ejection fraction (LVEF) is associated with increased risk of adverse events among patients undergoing percutaneous coronary intervention (PCI). Due to under-enrollment of females in randomized trials, there is limited data on the impact of LVEF on post-PCI outcomes in female patients. Purpose To evaluate the impact of varying degrees of LVEF impairment on 3-year outcomes in female patients undergoing PCI with drug-eluting stents (DES). Methods We pooled patient-level data of female patients from 26 randomized trials of coronary stents. The study population was stratified into three groups according to the 2016 European Society of Cardiology Heart Failure guidelines: LVEF ≥50% (normal), LVEF 40–49% (mid-range), and LVEF &amp;lt;40% (reduced). The primary outcome was major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction (MI), or stent thrombosis (ST) at 3-year follow-up. The Kaplan-Meier method was used for time-to-event analyses, with comparative risks being assessed using Cox regression. Results Out of 5672 female patients with available LVEF values at baseline, 4427 (78.1%) had normal LVEF, 602 (10.6%) had mid-range LVEF, and 643 (11.3%) had reduced LVEF. Patients with reduced LVEF were older and had a higher prevalence of smoking, prior MI, and multi-vessel disease. There was a stepwise increase in 3-year event rates moving from normal, to mid-range and reduced LVEF (Figure 1). After multivariable adjustment, hazard ratio (HR) for MACE was 1.45 (95% CI: 1.10–1.92) in patients with mid-range LVEF and 2.43 (95% CI: 1.84–3.22) in patients with reduced LVEF (trend p-value &amp;lt;0.0001). The risk of ST was more than doubled in both mid-range LVEF (HR 2.30, 95% CI: 1.30–4.06, p=0.004) and reduced LVEF patients (HR 2.18, 95% CI: 1.11–4.28, p=0.02), as compared with normal LVEF. Conclusion The presence of an even mild degree of LVEF impairment confers an increased risk of ischemic events, including ST, among females undergoing PCI with DES. Funding Acknowledgement Type of funding sources: None. Figure 1

Association of beta-blockers or inhibitors of renin-angiotensin system with clinical outcomes in patients with mid-range left ventricular ejection fraction after acute myocardial infarction

Abstract Background In the era of the initial optimal interventional and medical therapy for acute myocardial infarction (AMI), a number of patients with mid-range left ventricular ejection fraction (EF) (&amp;gt;40%, &amp;lt;50%) becomes increasing. Purpose This observational study aimed to investigate the association between oral beta-blockers or inhibitors of renin-angiotensin system (RAS) and 2-year clinical outcomes in patients with mid-range EF after AMI. Methods Among 13,624 patients enrolled in the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH), propensity-score matched patients who survived the initial attack and had mid-range EF were selected according to beta-blocker or RAS inhibitor therapy at discharge. Results Beta-blocker therapy at discharge was associated with lower 2-year major adverse cardiac events (MACE) of cardiac death, MI, revascularization or re-hospitalization due to heart failure (8.7 vs. 12.8/100 person-year; hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.50–0.93; P=0.015), and no significant interaction between EF ≤45% and &amp;gt;45% was observed (P for interaction=0.354). This association was mainly driven by lower MI in patients with beta-blockers (1.6 vs. 3.1/100 person-year; HR 0.50; 95% CI 0.26–0.95; P=0.035). Inhibitors of RAS at discharge were not associated with lower 2-year MACE, but with lower re-hospitalization due to heart failure (1.8 vs. 3.5/100 person-year; HR 0.53; 95% CI 0.33–0.86; P=0.010) without significant interaction between EF ≤45% and &amp;gt;45% (P for interaction=0.333). Conclusions Beta-blockers or RAS inhibitors at discharge were associated with better 2-year clinical outcomes without significant interaction between ≤45% and &amp;gt;45% in patients with mid-range EF after AMI.&amp;lt;/ef&amp;lt;50%)&amp;gt; Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Korea Centers for Disease Control and Prevention. 2-year clinical outcomes

STEMI with mid-range ejection fraction: a group of intermediate risk not to be forgotten

Abstract Background Reduced left ventricular ejection fraction (LVEF) &amp;lt;40% is an important negative prognostic factor in the setting of ST-elevation acute myocardial infarction (STEMI). On the other hand, data concerning mid-range LVEF (mrEF) post-STEMI are scarce. Consequently, recommendations regarding reassessment of LVEF or administration of neurohormonal medication in this group of patients (pts) are also lacking. Purpose To assess the current treatment and prognosis of STEMI with mrEF. Methods Retrospective study including all consecutive pts hospitalized for STEMI and submitted to primary percutaneous coronary intervention in a Cardiology centre in 2018. Pts were divided into 3 groups according to LVEF assessed before hospital discharge: preserved EF (pEF: LVEF ≥50%), mid-range EF (mrEF: LVEF 40–49%) and reduced EF (rEF: LVEF &amp;lt;40%). We analysed clinical characteristics, treatment, evolution of LVEF post-STEMI and clinical outcomes - death, myocardial infarction (MI) and hospitalization for heart failure (HF) – of the mrEF group and compared it with pEF. Results 188 pts with a mean age of 61 years were admitted for STEMI in 2018. The majority (58%, n=109) had pEF; 29% (n=55) had mrEF and 13% (n=24) were in the rEF group. Pts in the mrEF group had similar baseline characteristics to the others. However, compared with pEF, culprit-lesion was more often located in left main or left anterior descending arteries (80% vs 35%, p&amp;lt;0.001) and NT-proBNP levels were higher in mrEF pts (2270 vs 881 pg/mL, p&amp;lt;0.001). At discharge, all mrEF patients were medicated with a renin-angiotensin-aldosterone blocker and 91% with a beta-blocker. After a median of 8 months, LVEF improved a mean of 4% (± 9%) in the mrEF group. However, in 12.5% LVEF worsened to &amp;lt;40% (vs 0 in the pEF group, p=0.006). At a median follow-up of 2.6 years, there was an increase in mortality according to the EF group (pEF 4% vs mrEF 13% vs rEF 48%, log-rank: p&amp;lt;0.001 – fig. 1) with a hazard ratio (adjusted for age) of 3.75 (95% CI 1.1–12.8, p=0.035) for mrEF vs pEF. There was also a non-significant tendency to higher rates of the composite endpoint of MI and hospitalization for HF in the mrEF group vs pEF (8.2% vs 2.9%, p=0.213). Conclusions This study confirms previous reports of the worse prognosis of STEMI with mrEF and suggests the existence of a continuum of risk of adverse clinical outcomes according to LVEF. Therefore, this group of intermediate risk might also benefit from neurohormonal medication, which is only specifically recommended for rEF in current STEMI guidelines. It also highlights the importance of a closer follow-up (with reassessment of LVEF) of mrEF pts since a non negligeable proportion ultimately progress to rEF and may require additional medical treatment or even an implantable cardioverter defibrillator. Further research with larger samples is required to identify predictors of worsening LVEF and assess the impact of neurohormonal modulation in this population. Funding Acknowledgement Type of funding sources: None. Kaplan-Meier Survival Analysis

Mechanoenergetic coupling in heart failure with preserved, mid-range and reduced left ventricular ejection fraction

Abstract Background Heart failure (HF) classification based on left ventricular ejection fraction (LVEF) can vary because of changes in filling pressures, afterload, and contractile function. 11C-acetate positron emission tomography (PET) provides a load-independent measure of myocardial external efficiency (MEE) by simultaneous assessment of myocardial oxygen consumption (MVO2), cardiac work, left ventricular mass (LVM), end-systolic wall stress (ESWS), and myocardial blood flow (MBF). Purpose We aimed to characterize mechanoenergetic derangements in patients with HF and to study its interrelation with age, sex and obesity. Methods MEE was measured in 121 participants with 11C-acetate PET, and LVEF was acquired with echocardiography. We investigated healthy controls (n=20) and patients with HF and reduced LVEF &amp;lt;40% (HFrEF; n=25), mid-range LVEF 40–49% (HFmrEF; n=23), as well as patients with asymptomatic aortic valve stenosis (AS) and LVEF ≥50% (AS-asymp; n=38), and symptomatic AS and LVEF ≥50% (defined as HF with preserved LVEF (HFpEF); n=15). Results MEE declined in tandem with reduced LVEF from HFpEF and HFmrEF to HFrEF (p=0.041, p&amp;lt;0.001, and p&amp;lt;0.001 versus control, respectively; Figure 1). Impaired MEE was aggravated with increasing LVM (p=0.001) due to a disproportionate increase in overall left ventricular MVO2. In a multivariate analysis, female sex (p&amp;lt;0.001), a lower body mass index (p&amp;lt;0.001), and advanced age (p=0.01) were associated with a lower MEE (Figure 2). HFpEF, HFmrEF, and HFrEF patients had distinct energetic profiles involving MEE, MVO2, MBF, ESWS, and LVM (Figure 2). Conclusions Mechanoenergetic uncoupling was evident in every clinical state within the HF syndrome and associated with left ventricular hypertrophy and progressive systolic dysfunction. Sex, age, and obesity impacted myocardial energetics. To date, the present study is the largest investigation of mechanoenergetic coupling across several categories of patients with heart failure. 11C-acetate PET extends our pathophysiological comprehension of the HF syndrome beyond LVEF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Heart FoundationThe Lundbeck Foundation Relationship between LVEF and MEEMyocardial energetics in heart failure

Interim Results of the BYHEART Observational Study: Exogenous Phosphocreatine Effect on the Quality of life of Patients with Chronic Heart Failure.

Aim Improvement of quality of life is one of the most important goals for the treatment of patients with chronic heart failure (CHF). This study searched for ways to increase the efficiency of CHF treatment based on parameters of quality of life in CHF patients during and after the treatment with exogenous phosphocreatine (EP).Material and methods The effect of a single course of EP treatment on quality of life of patients with functional class (FC) II-IV CHF with reduced or mid-range left ventricular ejection fraction was studied as a part of the all-Russia prospective observational study BYHEART. The presence of FC II-IV CHF and a left ventricular ejection fraction &lt;50 % were confirmed by results of 6-min walk test (6MWT) and findings of echocardiography after stabilization of the background therapy.Results An interim data analysis showed that the course of EP treatment was associated with a significant improvement of quality-of-life indexes as determined by the Minnesota Living with Heart Failure Questionnaire (LHFQ) total score. These indexes significantly increased and remained at a satisfactory level for 6 mos. following completion of the treatment course. Also, the treatment significantly beneficially influenced the clinical condition of patients (heart failure severity scale), results of 6MWT, and the increase in left ventricular ejection fraction.Conclusion The conclusions based on results of the interim analysis should be confirmed by results of the completed study. Complete results are planned to be published in 2022.

Chronic Heart Failure in Patients with Arterial Hypertension Associated with Obstructive Sleep Apnea Syndrome: Possible Options to Pathogenetic Therapy

Aim. To study approaches to the treatment of chronic heart failure (CHF) with reduced and mid-range left ventricular ejection fraction (LVEF) in patients with arterial hypertension (AH) against the background of obstructive sleep apnea (OSA).Material and methods. The study included 136 patients with CHF and AH. Inclusion criteria for the study: 1) moderate and severe OSA (with an apnea/hypopnea index of more than 15 per hour); 2) II-IV functional class of CHF according to NYHA; 3) the level of brain natriuretic peptide precursor (NT-proBNP) ≥125 pg/ml; 3) LVEF &lt;50%; 4) the duration of hypertension is at least 2 years. Patients received drug therapy, including beta-blockers, mineralocorticoid receptor antagonists, diuretics, ACE inhibitors or angiotensin receptor inhibitors or valsartan/sacubitrile. After 12 months of followup, the patients were divided into 2 groups depending on the medication being administered. Group 1 included patients (n = 50) receiving therapy with valsartan/sacubitril, group 2 included patients (n = 86) receiving therapy without this drug. Effective CPAP-therapy also was registered in each group.Results. In patients with CHF who received valsartan/sacubitril, disease progression was recorded in 28% of cases, while in patients who did not receive therapy with this drug, an unfavorable course of CHF was recorded in 42.8% (p = 0.001). In group 1, the NT-proBNP level significantly (p = 0.034) decreased by 34%, while in group 2, a significant (p = 0.002) increase in biomarker levels was revealed by 35.5%. In the group of patients receiving therapy with valsartan/sacubitril an increase in LVEF (p = 0.007) was revealed by 12.5%. In group 1, an increase in exercise tolerance was achieved in the form of a significant (p = 0.012) increase in the distance of the six-minute walk test by 18.2%, while in group 2, the six-minute walk distance decreased by 19.2% (p = 0.034). In the subgroup of patients receiving CPAP therapy in combination with valsartan/sacubitril therapy (n=8), LVEF increased by 11.6% (p = 0.043), the six-minute walk test distance increased by 29.7% (p = 0.046), and NT-proBNP decreased by 22.5% (p = 0.039), while in the group of patients who received only CPAP therapy (n=19).Conclusion. The most significant slowdown in the rate of progression of CHF in patients with AH associated with OSA, an increase in exercise tolerance, as well as the most pronounced tendency to the reverse development of pathological echocardiographic changes in the myocardium when using valsartan/sacubitrile in drug therapy in combination with effective hardware CPAP therapy.

Pulmonary Hypertension in Patients With Heart Failure With Mid-Range Ejection Fraction.

Pulmonary hypertension (PH) is common in patients with heart failure (HF). The role of PH in patients with HF with reduced (HFrEF) and preserved (HFpEF) left ventricular ejection fraction (LVEF) has been extensively characterized during the last years. In contrast, the pathophysiology of HF with mid-range LVEF (HFmrEF), and in particular the role of PH in this context, are largely unknown. There is a paucity of data in this field, and the prevalence of PH, the underlying mechanisms, and the optimal therapy are not well-defined. Although often studied together there is increasing evidence that despite similarities with both HFrEF and HFpEF, HFmrEF also differs from both entities. The present review provides a summary of the current concepts of the mechanisms and clinical impact of PH in patients with HFmrEF, a proposal for the non-invasive and invasive diagnostic approach required to define the pathophysiology of PH and its management, and a discussion of future directions based on insights from mechanistic studies and randomized trials. We also provide an outlook regarding gaps in evidence, future clinical challenges, and research opportunities.

Prognostic significance of liver stiffness assessed by fibrosis‐4 index in patients with heart failure

BackgroundHeart failure (HF)‐related congestive hepatopathy is a well‐recognized problem in management of HF. The fibrosis‐4 (FIB4) index calculated by [age × aspartate aminotransferase (IU/L)/platelet count (109/L) × square root of alanine aminotransferase (IU/L)] is useful for evaluating liver stiffness. We aimed to investigate the impact of the FIB4 index on prognosis in patients with HF.Methods and resultsConsecutive HF patients referred for hospitalization at Kumamoto University Hospital, Japan, were registered between 2006 and 2015. We observed cardiovascular outcomes in each type of HF [HF with reduced left ventricular ejection fraction (LVEF) (HFrEF), HF with mid‐range LVEF (HFmrEF) and with preserved LVEF (HFpEF)] according to their FIB4 index; Group 1 (FIB4 index <1.3), Group 2 (FIB4 index: 1.3–2.67), and Group 3 (FIB4 index >2.67). This study enrolled 83 HFrEF patients, 117 HFmrEF patients, and 504 HFpEF patients. In HFpEF patients, the Kaplan–Meier curve revealed that Group 3 had a significantly higher rate of total cardiovascular events compared with the other two groups. By contrast, the occurrences of total cardiovascular events were not different among three groups in HFrEF and HFmrEF patients.Multivariate Cox proportional hazard analysis with significant factors in univariate analysis identified that the FIB4 index as an independent and significant predictor for future total cardiovascular events in HFpEF patients (hazard ratio: 1.09, 95% confidence interval: 1.03–1.15, P = 0.001).ConclusionsThe FIB4 index was a significant predictor for total cardiovascular events in HFpEF.

Clinical profile and causes of death according to ejection fraction in patients with heart failure cared for in a specialized Cardiology unit

Background and objectivePatients with heart failure are classified into three phenotypes based on left ventricular ejection fraction. This work aimed to compare the clinical profile, treatment, prognosis, and causes of death of patients with heart failure and reduced (<40%, HF-rEF), preserved (≥50%, HF-pEF), or mid-range (40–49%, HF-mrEF) left ventricular ejection fraction. MethodsAn analysis was conducted on the clinical data included in a prospective registry of patients with heart failure who were referred to a specific Cardiology unit from 2010 to 2019. ResultsA total of 1404 patients with HF-rEF, 239 patients with HF-mrEF, and 266 patients with HF-pEF were analyzed. Significant differences were observed among the groups in regard to several clinical characteristics and the frequency of prescription of neurohormonal blocking drugs. A multivariate Cox regression revealed an increased risk of all-cause mortality in patients with HF-pEF (hazard ratio 1.36; 95% confidence interval 1.03–1.80; p = 0.028) and patients with HF-mrEF (hazard ratio 1.36; 95% confidence interval 1.03–1.78; p = 0.029) as compared to patients with HF-rEF. Heart failure was the most frequent cause of death in the three subgroups. A higher relative weight of sudden death as a cause of death was observed among patients with HF-rEF while the relative weight of non-cardiovascular causes of death was higher among patients with HF-pEF and HF-mrEF. ConclusionsThis study confirms the existence of significant differences among patients with HF-rEF, HF-mrEF, and HF-pEF with regard to their clinical profile, therapeutic management, prognosis, and causes of death.