Mid-range Ejection Fraction Research Articles

Abstract 13558: Opening the Black Box of Artificial Intelligence: Visualization of Detecting Heart Failure Subtypes Using Electrocardiography

Objectives: To evaluate and visualize how artificial intelligence (AI) recognizes electrocardiography (ECG) characteristics of each heart failure (HF) subtype. We developed a visually explainable and interpretable AI-ECG algorithm for various HF subtypes to meet this need. This study proposes the ShapeExplainer (SE) to interpret models. Methods: From 33,920 patients at two hospitals, we trained a convolutional neural network to identify patients with HF subtypes using ECG and clinical diagnosis. HF subtypes include heart failure with reduced ejection fraction (HFrEF), heart failure with mid-range ejection fraction (HFmrEF, and heart failure with preserved ejection fraction (HFpEF) ( Figure a ). To interprete each HF classifier model, SE, which converts non-HF group data to be recognized as each HF subtype by each classifier, was trained. The converted fake ECG shows what the change is for the classifier to recognize as each HF subtype. SE from the non-HF group of the external validation set shows the result by comparing the shape before and after transformation. Results: When tested on an independent set of 6,784 patients, the network model yielded values for the area under the curves of HFrEF of 0.945, HFmrEF of 0.884, and HFpEF of 0.859, respectively. The results of each classifier were visualized by overlapping the original and newly generated ECGs. Comparing each subtype and its fake ECG, there was no clear trend of electrocardiographic features. However, fake ECG showed a tendency of qrs amplitude as it progressed to non-HF, HFpEF, HFmrEF, and HFrEF, especially in T wave or ST-change ( Figure b ). Conclusions: The proposed fake ECG generating method is a new approach for interpreting the AI-ECG model, helping physicians understand how AI recognizes HF subtypes.

Abstract 14374: Clinical and Echocardiographic Characteristics of Patients Who Develop Post Liver Transplant Non-Ischemic Cardiomyopathy

Background: Non-ischemic cardiomyopathy is a well-known but poorly understood cardiac complication post orthotopic liver transplantation (OLT). Methods: We performed a nested case control study in a cohort of 590 patients who underwent OLT at Loma Linda University between 2013 - 2021. 29 (4.9%) patients developed post-OLT non-ischemic cardiomyopathy. 100 patients who did not develop cardiomyopathy were selected randomly from the cohort to serve as control group. Clinical characteristics of cases and controls were compared and echocardiograms of patients who developed cardiomyopathy reviewed. Results: Patients who developed cardiomyopathy were more likely to be female, less likely to have history of hypertension, had lower baseline hemoglobin and platelets, and higher MELD scores ( Table 1) . Mean pre-transplant ejection fraction (EF) was 69% among patients who developed cardiomyopathy. Cardiomyopathy developed on average 10 days after OLT with mean EF dropping to 26%. 24 (83%) patients had reduced EF (<40%) and 5 (17%) had mid-range EF (40-49%). Wall motion analysis revealed global hypokinesis in 11 (38%) patients, mid-ventricular takotsubo in 11 (38%) patients, apical takotsubo in 5 (17%) patients, and basal takotsubo in 2 (7%) patients (Figure 1) . 24 (83%) patients recovered EF (≥ 50%) on average of 113 days after initial diagnosis of cardiomyopathy. Conclusions: Female sex and higher MELD scores were associated with development of non-ischemic cardiomyopathy post OLT. Global hypokinesis and mid-ventricular takotsubo were the most common patterns of wall motion abnormality. EF recovery was noted in majority of patients indicating operative stress related etiology.

Abstract 14332: Syncope, Storm, and Shock: Fulminant Myocarditis

A 46-year-old female with prediabetes and recent hysterectomy three weeks prior presented to the hospital for syncope. Patient reported no chest pain or dyspnea but complained of intermittent palpitations. The patient developed runs of non-sustained ventricular tachycardia which quickly escalated into incessant ventricular tachycardia (VT). Unresponsive to maximal medical therapy, the patient was cardioverted, intubated and sedated. Electrocardiogram was obtained which showed ST segment elevation in V1 and V2 without reciprocal changes. Bedside point-of-care ultrasound was negative for wall motion abnormalities. Laboratory results were significant for normal electrolytes, elevated troponins peaking at 7.14 ng/mL the following morning, and lactic acid of 3.2 mmol/L. Patient was initiated on vasopressor and ionotropic support for suspected shock. Left heart catheterization was negative for obstructive coronary artery disease. Right heart catheterization revealed mild pulmonary hypertension and biventricular failure. Formal echocardiogram revealed mid-range ejection fraction with a small pericardial effusion. The patient’s clinical status was deteriorating and revealed multiorgan failure. In conjunction with advanced heart failure and mechanical circulatory support teams, veno-arterial extracorporeal membrane oxygenation was initiated with subsequent implantation of intra-aortic balloon pump. High-dose steroids were given while awaiting transfer to a quaternary center. The patient is currently being evaluated for endomyocardial biopsy and evaluation of left ventricular assist device or heart transplantation due to fulminant myocarditis (FM). FM requires early recognition, intensive support, and further investigation for optimal management.

Abstract 12393: Two-Year Clinical Outcome of Mid-Range Ejection Fraction at Admission in Patients With Acute Myocardial Infarction

Introduction: The American Heart Association and European Society of cardiology guidelines reclassified heart failure according to left ventricular ejection fraction, recognizing patients with mid-range EF (mrEF; 40% to 49%) as a distinct group. However, studies on the clinical characteristics of mid-range EF patients and the occurrence of cardiovascular events in acute MI patients are insufficient. Methods: We categorized 6,553 patients with acute myocardial infarction (AMI) from the Korea AMI-National Institutes of Health between November 2011 and December 2015 into three groups (reduced EF ; LVEF < 40% at admission, mild-reduced EF ; LVEF 40 to 49%, preserved EF ;LVEF ≥50%). The primary endpoint was defined as any death at two-year. Secondary endpoints were defined as any myocardial infarction, any revascularization, patient-oriented composite outcome(POCE). Results: Compared to patients with other two groups, the reduced EF group had a highest overall mortality, POCE, and any MI (24.7% vs 8.3% vs 4.6%, p < 0.0001, 33.0% vs 15.6% vs 12.4%, p<0.0001, 3.9% vs 2.7% vs 2.6%, p<0.0046). When mid-range EF group was designated as a reference, in multivariate analysis including all variables, significant differences with HFrEF group was found. (Hazard ratio ). When compared with HFpEF, only Model 1 and Model 2 showed a significant statistical difference (Model 1 ; 0.65 (0.53-0.81), Model 2 ; 0.56 (0.56-0.86). Conclusions: Followed up for two years, significant differences in survival rates were observed between the mid-range EF, reduced EF, and preserved EF group. After adjusting for common prognostic factors affecting the overall mortality rate, the reduced EF group had a significantly higher mortality rate than mid-range EF group, but no significant difference was observed between the preserved EF and the mid-range EF group.

Cardiovascular magnetic resonance phenotyping of heart failure with mildly reduced ejection fraction.

The 2016 European Society of Cardiology Heart Failure Guidelines defined a new category: heart failure with mid-range ejection fraction (HFmrEF) of 40-49%. This new category was highlighted as having limited evidence and research was advocated into underlying characteristics, pathophysiology, and diagnosis. We used multi-parametric cardiovascular magnetic resonance (CMR) to define the cardiac phenotype of presumed non-ischaemic HFmrEF. Patients (N = 300, 62.7 ± 13 years, 63% males) with a clinical diagnosis of heart failure with no angina symptoms, history of myocardial infarction, or coronary intervention were prospectively recruited. Patients underwent clinical assessment and CMR including T1 mapping, extracellular volume (ECV) mapping, late gadolinium enhancement, and measurement of myocardial blood flow at rest and maximal hyperaemia. Of 273 patients in the final analysis, 93 (34%) patients were categorized as HFmrEF, 46 (17%) as heart failure with preserved ejection fraction (HFpEF), and 134 (49%) as heart failure with reduced ejection fraction (HFrEF). Nineteen (20%) patients with HFmrEF had evidence of occult ischaemic heart disease. Diffuse fibrosis and hyperaemic myocardial blood flow were similar in HFmrEF and HFpEF, but HFmrEF showed significantly lower native T1 (1311 ± 32 vs. 1340 ± 45 ms, P < 0.001), ECV (24.6 ± 3.2 vs. 26.3 ± 3.1%, P < 0.001), and higher myocardial perfusion reserve (2.75 ± 0.84 vs. 2.28 ± 0.84, P < 0.001) compared with HFrEF. Patients with HFmrEF share most phenotypic characteristics with HFpEF, including the degree of microvascular impairment and fibrosis, but have a high prevalence of occult ischaemic heart disease similar to HFrEF. Further work is needed to confirm how the phenotype of HFmrEF responds to medical therapy.

Comparison of Patients with Reduced and Mildly Reduced Left Ventricular Ejection Fraction: Intermediate Data from the FAR NHL Registry

Introduction: We present the results of a study by the Pharmacology and NeuroHumoral Activation Registry (FAR NHL), which collects data on patients with chronic heart failure. The register contains 1088 patients from three workplaces in the Czech Republic which specialize in the care of patients with heart failure. Objectives: The aim was to obtain a comparison of pharmacotherapy and the incidence of comorbidities in patients with reduced ejection fraction (HFrEF) versus patients with mid-range (or newly mildly reduced) ejection fraction (HFmrEF). Methods: Patients with a baseline left ventricular ejection fraction below 50% were included and divided into HFrEF with EF below 40% and HFmrEF with EF 40–49%, according to the 2016 ESC Guidelines. In addition to the clinical condition, we also monitored laboratory parameters, comorbidities and pharmacotherapy in the patients. Results: Patients with HFrEF versus HFmrEF are more likely to be male (p &lt; 0.008), younger (p &lt; 0.001), have lower systolic blood pressure and are less likely to have ischemic etiology of heart failure (p &lt; 0.001). There were no differences between the groups in the proportion of comorbidities: hypertension, diabetes mellitus, dyslipidemia, ischemic lower limb disease or chronic obstructive pulmonary disease. There were no differences in the proportion of smokers and non-smokers between the groups. Patients with HFrEF have a higher class of New York Heart Association (NYHA), a level of N-terminal fraction of natriuretic peptide B (NT-proBNP), and a higher level of urea and uric acid. They are more often treated with loop diuretics or mineral corticosteroid receptor (MRA) blockers and less often with thiazides (p &lt; 0.001), and also have a worse two-year prognosis. Conclusion: Compared to patients with HFmrEF, patients with HFrEF have more severe heart failure, more pronounced neurohumoral activation and a worse prognosis. They do not differ in the presence of comorbidities.

Heart failure with mildly reduced ejection fraction: not a mid-range prognosis

Abstract Introduction Heart failure with mildly reduced ejection fraction (HFmrEF) has been recognized in the last heart failure guidelines of the European Society of Cardiology, replacing the concept of “midrange ejection fraction”. There is limited data regarding mortality outcomes of HFmrEF compared to heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fraction. Purpose We aimed to evaluate whether HFmrEF has a different prognosis after an acute heart failure (AHF) episode, in a real-world contemporaneous southern European population. Methods We retrospectively studied 1026 patients admitted to our emergency department between November 2016 and December 2017 with discharge diagnosis of AHF. Median follow up was 5 months (IQR 3–11 months). Incidence of rehospitalization, cardiovascular (CV) and all-cause mortality were evaluated through multivariable logistic regression models and by Kaplan-Meyer survival curves. Results From all patients, 782 were categorized in HFrEF (34.1%), HFmrEF (19.4%) and HFpEF (46.4%). There was heterogeneity between groups. Compared to HFrEF, HFmrEF patients were older (80 [74–84] vs. 76 [67–82] years, p&amp;lt;0.001), with lower prevalence of males (61.2% vs. 76.4%, p=0.004) and coronary artery disease (CAD) (35.5% vs. 47.6%, p=0.024), but higher rates of valvular heart disease (VHD) (48.0% vs. 29.6%, p&amp;lt;0.001). Compared to HFpEF, HFmrEF subjects had higher prevalence of males (61.2% vs. 40.8%, p&amp;lt;0.001) and CAD (35.5% vs. 13.2%, p&amp;lt;0.001). At admission, patients with HFmrEF and HFrEF had similar serum creatinine e B-type natriuretic peptide values, but higher than the HFpEF group: 1.38±0.7 vs. 1.45±0.7 vs. 1.28±0.8mg/dL, p=0.019 and 701 [385–1191] vs. 1000 [494–1776] vs. 360 [214–717]pg/mL, p&amp;lt;0.001, respectively. HFmrEF patients had higher rates of hospitalization (71.7% vs. 43.8%, p&amp;lt;0.001), follow-up readmissions (27.6% vs. 18.7%, p=0.034), CV (11.8% vs. 5.0%, p=0.025) and all-cause mortality (25.7% vs. 14.9%, p=0.015), compared to HFpEF; no differences comparatively to HFrEF. There was no difference between groups regarding the length of hospitalization (9 [5–15] vs. 8 [5–15] vs. 10 [6–17] days, p=0.302). In multivariate logistic regression model adjusted for age, sex, SBP, CAD, VHD, creatinine, and BNP, HFmrEF increased the risk of CV (OR 2.9, 95% CI 1.2–6.7, p=0.016) and all-cause mortality (OR 2.1, 95% CI 1.2–3.9, p=0.011), but not follow-up readmissions (OR 1.7, 95% CI 0.9–2.9, p=0.059). Kaplan-Meier estimates of CV, and all-cause mortality are shown in Figure 1. Conclusions HFmrEF have a similar prognosis to HFrEF and worse than HFpEF, with more readmissions, CV and all-cause mortality, after an AHF episode. Funding Acknowledgement Type of funding sources: None.

Clinical outcomes and structural remodelling after ablation of atrial fibrillation in heart failure with mildly reduced or mid-range ejection fraction.

The efficacy of catheter ablation (CA) on clinical outcomes and cardiac structural remodelling in atrial fibrillation (AF) patients with HF with mildly reduced or mid-range ejection fraction (HFmrEF) remains unclear. We aimed to compare the efficacy of CA with medical therapy (MT) in AF patients with HFmrEF. We retrospectively screened a total of 36879 patients with AF between 2005 and 2020. Patients who were initially diagnosed with echocardiography-proved HFmrEF and had follow-up echocardiography were enrolled. After applying propensity score matching in a 1:1 ratio, 72 patients treated by CA (Group 1) and 72 patients receiving MT (Group 2) were taken into further analysis. The co-morbidities were similar between the two groups, except for hyperlipidaemia. After a mean follow-up duration of 58.9±42.6months, Group 1 had a lower HF hospitalization and all-cause mortality compared with Group 2 (hazard ratio (HR), 0.089 [95% confidence interval (CI), 0.011-0.747]; P=0.026 and HR, 0.121 [95% CI, 0.016-0.894]; P=0.038, respectively). As for cardiac structural remodelling, the Group 1 had a better improvement in left ventricular ejection fraction (LVEF) and a more decreased left atrium (LA) diameter than Group 2 (+25.0%±18.0% vs. +6.2%±21.6%, P=<0.0001 and -1.6±4.7mm vs. +1.5±8.2mm, P=0.008, respectively). In patients with HFmrEF and AF, CA of AF could reduce both HF hospitalization and all-cause mortality as compared with those with MT. A significant improvement in LVEF and decrease in LA diameter were also observed in the CA group. Early rhythm control with CA should be taken into consideration in patients with HFmrEF and AF.

Starting Neurohormonal Antagonists in Patients With Acute Heart Failure With Mid-Range and Preserved Ejection Fraction.

The clinical benefits of neurohormonal antagonists for patients with heart failure (HF) with mid-range and preserved ejection fraction (HFmrEF and HFpEF) are uncertain. This study analyzed 858 consecutive patients with HFmrEF (EF: 40-49%) or HFpEF (EF ≥50%), who were hospitalized for acute HF, and who were discharged alive, and were not taking angiotensin-converting enzyme inhibitors (ACE)-I/ angiotensin II receptor blockers (ARB) or β-blockers at admission. The study population was classified into 4 groups according to the status of prescription of ACE-I/ARB and β-blocker at discharge: no neurohormonal antagonist (n=342, 39.9%), ACE-I/ARB only (n=128, 14.9%), β-blocker only (n=189, 22.0%), and both ACE-I/ARB and β-blocker (n=199, 23.2%) groups. The primary outcome measure was a composite of all-cause death or HF hospitalization. The cumulative 1-year incidence of the primary outcome measure was 41.2% in the no neurohormonal antagonist group, 34.0% in the ACE-I/ARB only group, 28.6% in the β-blocker only group, and 16.4% in the both ACE-I/ARB and β-blocker group (P<0.001). Compared with the no neurohormonal antagonist group, both the ACE-I/ARB and β-blocker groups were associated with a significantly lower risk for a composite of all-cause death or HF hospitalization (HR: 0.46, 95% CI: 0.28-0.76, P=0.002). In hospitalized patients with HFmrEF and HFpEF, starting both ACE-I/ARB and a β-blocker was associated with a reduced risk of the composite of all-cause death or HF hospitalization compared with patients not starting on an ACE-I/ARB or β-blocker.

Long-Term prognosis of radiofrequency catheter ablation for atrial fibrillation with different subtypes of heart failure in the era of ablation index guidance.

BackgroundThe long-term outcomes of ablation index (AI)-guided radiofrequency catheter ablation (RFCA) on atrial fibrillation (AF) and different subtypes of heart failure (HF) remain unknown. The aim of the study was to evaluate the long-term prognosis of AI-guided RFCA procedures in patients with AF and concomitant HF.MethodsWe retrospectively included consecutive patients with AF and HF who underwent the initial RFCA procedure with AI guidance from March 2018 to June 2021 in our institution. The patients were categorized into two groups: HF with preserved ejection fraction (HFpEF) group and HF with mid-range ejection fraction (HFmrEF) +HF with reduced ejection fraction (HFrEF) group.ResultsA total of 101 patients were included. HFpEF and HFmrEF + HFrEF groups consisted of 71 (70.3%) and 30 patients (29.7%), respectively. During a median follow-up of 32.0 (18.2, 37.6) months, no significant difference was detected in AF recurrence between groups (21.1 vs. 33.3%) after multiple procedures, whereas the incidence of the composite endpoint of all-cause death, thromboembolic events, and HF hospitalization was significantly lower in HFpEF group (9.9 vs. 25.0%, Log-rank p = 0.018). In multivariable analysis, a history of hypertension [hazard ratio (HR) 4.667, 95% confidence interval (CI) 1.433–15.203, p = 0.011], left ventricular ejection fraction (LVEF) < 50% (HR 5.390, 95% CI 1.911–15.203, p = 0.001) and recurrent AF after multiple procedures (HR 7.542, 95% CI 2.355–24.148, p = 0.001) were independently associated with the incidence of the composite endpoint.ConclusionLong-term success could be achieved in 75% of patients with AF and concomitant HF after AI-guided RFCA procedures, irrespective of different HF subtypes. Preserved LVEF was associated with a reduction in the composite endpoint compared with impaired LVEF. Patients with recurrent AF tend to have a poorer prognosis.

Prevalence, treatment, and 1-year outcomes of heart failure with mid-range ejection fraction

Background: The prevalence of patients with heart failure with mid-range ejection fraction (HFmrEF) remains unchanged regardless of healthcare strategies. HFmrEF has mixed characteristics of heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). The treatment of HFmrEF was recommended to be similar to the treatment of HFpEF in the 2016 guidelines of the European Society of Cardiology (ESC) but was changed to those of HFrEF in the 2021 version. Objective: To describe the clinical characteristics of inpatients with HFmrEF with a focus on treatment practices. Methods: A prospective study was conducted on patients diagnosed with HFmrEF who were admitted to the cardiology department of Nhan Dan Gia Dinh hospital from July 2019 to July 2020. Rehospitalization and mortality were followed up by telephone after 1 year. Results: Of a total of 529 heart failure cases admitted to the hospital during the study period, there were 73 patients (13.8%) with HFmrEF. The mean age was 68 years and males comprised 53%. The average hospitalization stay length was 6.7 days. The most common precipitating factors of heart failure were non-adherence (42.5%) and infection (39.7%) followed by hypertensive crisis (8.2%), anemia (6.8%), acute myocardial infarction (5.5%), arrhythmia (4.1%), and hyperthyroidism (2.7%). Ischemic heart disease was the leading cause (61.6%) of HFmrEF, followed by hypertension (12.3%). The rates of HFmrEF patients treated with beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and aldosterone receptor antagonists were 76.1%, 76.71%, 37.73%, and 47.95%, respectively. There were no statistically significant differences in the guideline-directed medical therapy (GDMT) medications administered between HFmrEF due to ischemic and non-ischemic causes. After 1-year follow-up, the combined outcome of rehospitalization and mortality in HFmrEF was 24.7%. Conclusion: The treatment of HFmrEF was similar to that of HFrEF between 2019 and 2020 at Nhan Dan Gia Dinh hospital and was in accordance with the 2021 ESC guidelines.

Long-term mortality in heart failure with mid-range ejection fraction: systematic review and meta-analysis.

Heart failure patients with mid-range ejection fraction (HFmrEF) have overlapping clinical features, compared with patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). We aim to perform a meta-analysis of studies reporting long-term outcomes in HFmrEF compared with HFrEF and HFpEF. Data from 18 eligible large-scale studies including 126239 patients were pooled. Patients with HFmrEF had a lower risk of all-cause death than those with HFrEF [risk ratio (RR)=0.92; 95% CI=0.85-0.98; P<0.001]. This significant difference was seen in the follow-up at 1, 2, and 3years. Patients with HFmrEF had significantly lower risk of cardiovascular (CV) deaths than HFrEF (RR=0.77; 95% CI=0.65-0.92; P<0.001). Subgroup analysis showed that studies recruiting >50% of males had higher risk of deaths with HFrEF (RR=1.15; 95% CI=1.04-1.26; P=0.006). When compared with HFpEF, patients with HFmrEF had comparable risk of all-cause death (RR=1.02; 95% CI=0.96-1.09; P=0.53). Similarly, there were no differences in the 1, 2, and 3year deaths; CV and non-CV deaths were insignificant between HFmrEF and HFpEF. The results of the study support that HFmrEF has better prognosis than HFrEF but similar prognosis when compared with HFpEF. Gender disparity between studies seems to influence the results between HFmrEF and HFrEF. Transition in left ventricular ejection fraction (LVEF), which could not be addressed in the study, may play a decisive role in determining outcomes. PROSPERO review registration number CRD42021277107.

Correlation between heart rate index, SBPpeak-to-SBPrest ratio and peak oxygen consumption in patients with chronic heart failure

Objective: To investigate the correlation between heart rate index (HRI), systolic blood pressure(SBP) peak-to-SBPrest ratio (SBPR) and peak oxygen consumption (peakVO2) in patients with chronic heart failure (CHF), and discuss the possibility of using HRI and SBPR collected during exercise to assess the exercise tolerance of CHF patients in the absence of gas analysis. Methods: In this cross-sectional study, a total of 547 patients with CHF who underwent cardiopulmonary exercise test(CPET) in Tongji Hospital Heart Rehabilitation Center Affiliated to Tongji University from March 2007 to December 2018 were collected retrospectively, focusing on their clinical data including age, gender, type of heart failure,BMI as well as data collected during their CPETs, such as peakVO2, HRI and SBPR. Spearman univariate correlation analysis was used for statistical analysis, to unveil the correlations between peakVO2 and those parameters, and multiple linear regression analysis was also conducted. Results: A total of 547 CHF patients conducting CPET were included in this research, of which 447 were male, at age of 63(56, 69). Univariate analysis indicates that HRI, SBPR and peakVO2 showed significant positive correlation (r=0.323, 0.263, respectively, all P<0.001); Age and peak VO2 showed significant negative correlation(r=-0.207, P<0.001); Male patients showed peakVO2 higher than female(r=-0.229, P<0.001); PeakVO2 of heart failure with reduced ejection fraction(HFrEF) was lower than heart failure with mid-range ejection fraction(HFmrEF)and heart failure with preserved ejection fraction(HFpEF) (r=0.181, P<0.001). Body mass index (BMI) had no significant correlation with peakVO2 (P>0.05). Multivariate linear regression analysis showed that the HRI, SBPR were positively correlated with peakVO2(t=7.68, 5.08, respectively, all P<0.05), while age and BMI showed negative correlation with peakVO2(t=-5.43, -0.31, respectively, all P<0.05). PeakVO2 of male was higher than female(t=-6.03, P<0.05), and peakVO2 of HFrEF was lower than those of HFmrEF and HFpEF(t=3.17, 4.48, respectively, all P<0.05). A linear equation (F=33.52, adjusted R2=0.29) could be constructed: peakVO2=10.65(male) or 8.53(female)+4.26HRI+3.31SBPR-0.07age-0.13BMI+0(HFrEF) or 1.05 (HFmrEF) or 1.62(HFpEF). Conclusion: HRI and SBPR are positively correlated with peakVO2. In the absence of gas analysis, it is possible to apply HRI and SBPR during exercise to predict exercise tolerance in patients with CHF.

Association of Genetically Predicted Fibroblast Growth Factor-23 with Heart Failure: A Mendelian Randomization Study.

Elevated fibroblast growth factor-23 (FGF23) has been consistently associated with heart failure, particularly heart failure with preserved ejection fraction, among patients with CKD and in the general population. FGF23 may directly induce cardiac remodeling and heart failure. However, biases affecting observational studies impede robust causal inferences. Mendelian randomization leverages genetic determinants of a risk factor to examine causality. We performed a two-sample Mendelian randomization to assess causal associations between FGF23 and heart failure. Genetic instruments were genome-wide significant genetic variants associated with FGF23, including variants near PIP5K1B, RGS14, LINC01229, and CYP24A1. We analyzed data from the Heart Failure Molecular Epidemiology for Therapeutic Targets and BioVU biobanks to examine associations of the four variants with overall heart failure, heart failure with preserved ejection fraction, and heart failure with reduced and mid-range ejection fraction. We developed an eGFR polygenic risk score using summary statistics from the Chronic Kidney Disease Genetics Consortium (CKDGen) genome-wide association study of eGFR in >1 million individuals and performed stratified analyses across eGFR polygenic risk score strata. Genetically determined FGF23 was not associated with overall heart failure in the Heart Failure Molecular Epidemiology for Therapeutic Targets consortium (odds ratio, 1.13; 95% confidence interval, 0.89 to 1.42 per unit higher genetically predicted log FGF23) and the full BioVU sample (odds ratio, 1.32; 95% confidence interval, 0.95 to 1.84). In stratified analyses in BioVU, higher FGF23 was associated with overall heart failure (odds ratio, 3.09; 95% confidence interval, 1.38 to 6.91) among individuals with low eGFR-polygenic risk score (<1 SD below the mean), but not those with high eGFR-polygenic risk score (P interaction = 0.02). Higher FGF23 was also associated with heart failure with preserved ejection fraction among all BioVU participants (odds ratio, 1.47; 95% confidence interval, 1.01 to 2.14) and individuals with low eGFR-polygenic risk score (odds ratio, 7.20; 95% confidence interval, 2.80 to 18.49), but not those high eGFR-polygenic risk score (P interaction = 2.25 × 10-4). No significant associations were observed with heart failure with reduced and midrange ejection fraction. We found no association between genetically predicted FGF23 and heart failure in the Heart Failure Molecular Epidemiology for Therapeutic Targets consortium. In BioVU, genetically elevated FGF23 was associated with higher heart failure risk, specifically heart failure with preserved ejection fraction, particularly among individuals with low genetically predicted eGFR. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_07_28_CJN00960122.mp3.

Surgical treatment of patients with aortic valve disease complicated with moderate functional mitral regurgitation and heart failure with midrange ejection fraction: a cohort study.

Background Controversies exist on the treatment of moderate functional mitral regurgitation (FMR) in patients with severe aortic valve disease undergoing the aortic valve replacement (AVR). While a substantial proportion of these patients can be complicated with heart failure with midrange ejection fraction (HFmrEF), established studies show that the latter might compromise the patient outcome. This study was aimed to evaluate the prognostic value of concomitant mitral valve surgery during AVR in patients with severe aortic valve disease followed by moderate FMR and HFmrEF.MethodsA total of 78 consecutive patients were retrospectively recruited. Patients were divided into control (isolated AVR) and treatment (AVR + mitral valve surgery) groups. Follow-up outcomes were compared by Kaplan-Meier method, followed by multiple adjustment with inverse probability treatment weighting (IPTW) analysis. The primary outcome was the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE).ResultsThirty-six patients received isolated AVR, while 42 received AVR with mitral valve repair or replacement. The median follow-up time was 28.7 months. Unadjusted analysis showed that there was no significant difference in the rate of MACCE between the two groups [hazard ratio (HR): 1.14, 95% confidence interval (CI): 0.48–2.69, Plogrank=0.770], which was sustained in IPTW analysis (HR: 1.64, 95% CI: 0.59–4.55, Plogrank=0.342). In addition, while concomitant mitral valve surgery improved follow-up FMR more completely (P=0.026) in the IPTW analysis, the ejection fraction was comparable between the two groups (P=0.276). Furthermore, IPTW analysis also showed that mitral valve surgery was associated with the increased risk of postoperative acute kidney injury (P=0.007).ConclusionsIn patients with aortic valve disease followed by moderate FMR and HFmrEF, mitral valve surgery concomitant to AVR may not bring extra benefit in the MACCE-free survival and the improvement of HFmrEF. However, while concomitant mitral valve surgery has priority on the complete improvement of FMR, it might increase the risk of postoperative acute kidney injury.

Myocardial fibrosis markers changes in patients with heart failure with mid-range ejection fraction of ischemic genesis under therapy

Background and Aims : The aim of the study was to evaluate the therapy effectiveness by β-blockers bisoprolol or nebivolol in combination with eplerenone on myocardial fibrosis markers in patients with heart failure with mid-range ejection fraction (HFmrEF) and metabolic disorders.

Clinical characteristics of heart failure patients with mid-range ejection fraction

Background We aimed to characterise and compare the clinical profile of heart failure (HF) with mid-range (HFmrEF), reduced (HFrEF) and preserved (HFpEF) left-ventricular ejection fraction. Methods We conducted a descriptive, observational study in 267 HF patients admitted to the Internal Medicine department of a tertiary hospital during 2010–2016. The study population was divided into three groups according to the ejection fraction rate: HFrEF (<40%), HFmrEF (40–49%), and HFpEF (≥50%). We analysed and compared their demographic, clinical, and analytical characteristics. Results The mean age of the study population was 79.5 (standard deviation, 8.14) years; 56.6% were males. The most common phenotype was HFpEF (58.1%), followed by HFrEF (21.7%) and HFmrEF (20.2%). Ischaemic cardiopathy was the primary aetiology in the HFmrEF and HFrEF groups, and arterial hypertension in the HFpEF group. The most common comorbidities among HFmrEF patients were diabetes (43.4%), chronic obstructive pulmonary disease (35.8%), and anaemia (35.8%); 49.1% had impairment of segmental myocardial contractility, and 35.8% ventricular dilatation. No differences in HF outcomes were observed among the three phenotypes. Conclusion HFmrEF shows characteristics similar to both HFpEF and HFrEF. Further large-scale studies with longer follow-up are needed to ascertain if it is worth distinguishing this phenotype in clinical practice in terms of management and prognosis.

Cost-of-disease of Heart Failure in Turkey: A Delphi Panel-based Analysis of Direct and Indirect Costs.

Background:Heart failure (HF) is considered a significant public health issue with a substantial and growing epidemiologic and economic burden in relation to longer life expectancy and aging global population.Aims:To determine cost-of-disease of heart failure (HF) in Turkey from the payer perspective.Study Design:Cross-sectional cost of disease study.Methods:In this cost-of-disease study, annual direct and indirect costs of management of HF were determined based on epidemiological, clinical and lost productivity inputs provided by a Delphi panel consisted of 11 experts in HF with respect to ejection fraction (EF) status (HF patients with reduced EF (HFrEF), mid-range EF (HFmrEF) and preserved EF (HFpEF)) and New York Heart Association (NYHA) classification. Direct medical costs included cost items on outpatient management, inpatient management, medications, and non-pharmaceutical treatments. Indirect cost was calculated based on the lost productivity due to absenteeism and presenteeism.Results:51.4%, 19.5%, and 29.1% of the patients were estimated to be HFrEF, HFmrEF, and HFpEF patients, respectively. The total annual direct medical cost per patient was $887 and non-pharmaceutical treatments ($373, 42.1%) were the major direct cost driver. Since an estimated nationwide number of HF patients is 1,128,000 in 2021, the total annual national economic burden of HF is estimated to be $1 billion in 2021. The direct medical cost was higher in patients with HFrEF than in those with HFmrEF or HFpEF ($1,147 vs. $555 and $649, respectively). Average indirect cost per patient was calculated to be $3,386 and was similar across HFrEF, HFmrEF and HFpEF groups, but increased with advanced NYHA stage.Conclusion:Our findings confirm the substantial economic burden of HF in terms of both direct and indirect costs and indicate that the non-pharmaceutical cost is the major direct medical cost driver in HF management, regardless of the EF status of HF patients.

BLITZ-HF: a nationwide initiative to evaluate and improve adherence to acute and chronic heart failure guidelines.

To assess adherence to guideline recommendations among a large network of Italian cardiology sites in the management of acute and chronic heart failure (HF) and to evaluate if an ad-hoc educational intervention can improve their performance on several pharmacological and non-pharmacological indicators. BLITZ-HF was a cross-sectional study based on a web-based recording system with pop-up reminders on guideline recommendations used during two 3-month enrolment periods carried out 3 months apart (Phase 1 and 3), interspersed by face-to-face macro-regional benchmark analyses and educational meetings (Phase 2). Overall, 7218 patients with acute and chronic HF were enrolled at 106 cardiology sites. During the enrolment phases, 3920 and 3298 patients were included, respectively, 84% with chronic HF and 16% with acute HF in Phase 1, and 74% with chronic HF and 26% with acute HF in Phase 3. At baseline, adherence to guideline recommendations was already overall high for most indicators. Among acute HF patients, an improvement was obtained in three out of eight indicators, with a significant rise in echocardiographic evaluation. Among chronic HF patients with HF and preserved or mid-range ejection fraction, performance increased in two out of three indicators: creatinine and echocardiographic evaluations. An overall performance improvement was observed in six out of nine indicators in ambulatory HF with reduced ejection fraction patients with a significant increase in angiotensin receptor-neprilysin inhibitor prescription rates. Within a context of an already elevated level of adherence to HF guideline recommendations, a structured multifaceted educational intervention could be useful to improve performance on specific indicators. Extending this approach to other non-cardiology healthcare professionals, who usually manage patients with HF, should be considered.

Mild and moderate to severe early acute kidney injury following cardiac surgery among patients with heart failure and preserved vs. mid-range vs. reduced ejection fraction: A retrospective cohort study.

Patients with heart failure who undergo cardiac surgery have increased long-term mortality in which acute kidney injury (AKI) plays a role. However, little is known about whether the incidence of AKI differs according to stratified left ventricular ejection fraction (LVEF). To assess the risks of mild AKI and moderate to severe AKI postcardiac surgery among patients with heart failure. Retrospective cohort analysis of patient data. Ejection fractions were categorised as LVEF less than 40%, heart failure with reduced ejection fraction (HFrEF); LVEF 40 to 49%, heart failure with mid-range ejection fraction (HFmrEF); and LVEF at least 50%, heart failure with preserved ejection fraction (HFpEF). Patients who underwent cardiac surgery from 2012 to 2019 in Fuwai Hospital, Beijing, China, were consecutively enrolled. The primary endpoint was postoperative AKI staged either as mild AKI or moderate to severe AKI. The secondary outcome was the peri-operative composite adverse event of dialysis support, tracheotomy, intrasurgical and postsurgical mechanical cardiac support and in-hospital mortality. This study also assessed chronic renal dysfunction at follow-up. Of the 54 696 included patients, 18.9% presented with heart failure. Among these with HFpEF, HFmrEF and HFrEF, the incidence of postoperative mild AKI was 37.0, 33.4 and 37.6%, respectively. Patients with HFpEF and HFmrEF were characterised by numerically greater prevalence of moderate to severe AKI than HFrEF (8.5 vs. 9.1 vs. 5.8%). HFrEF and HFmrEF patients had comparable risks for mild AKI relative to HFpEF patients, odds ratio (OR) 0.885; 95% confidence interval CI 0.763 to 1.027 for HFmrEF vs. HFpEF; OR 1.083; 95% CI 0.933 to 1.256 for HFrEF vs. HFpEF. Patients with HFmrEF were more at risk for moderate to severe AKI than patients with HFpEF (OR, 1.368; 95% CI 1.066 to 1.742), but HFrEF and HFpEF did not differ significantly (OR 1.012; 95% CI 0.752 to 1.346). An increasing number of noncardiac comorbidities led to a higher risk of mild AKI and moderate to severe AKI in patients with heart failure; and its effect on AKI was almost equal among the three heart failure strata. The incidence of postoperative composite adverse outcome increased in a graded manner from HFpEF to HFmrEF to HFrEF. Information on the creatine concentrations at 3 months postoperatively and longer were retained for 5200 out of 10 347 (50.6%) heart failure patients in our charts.The AKI severity and the presence of HFmrEF contributed substantially to the development of renal dysfunction over a median [IQR] follow-up of 10 months [4.0 to 21.0]. Initiative programmes aimed at patients with HFrEF to prevent moderate to severe AKI and chronic kidney dysfunction should also include patients with HFmrEF.