Heart Failure With Preserved Ejection Fraction Group Research Articles

Abstract 13703: Outpatient Cardiac Rehabilitation Reduces Heart Failure Re-Hospitalization in Patient With Heart Failure With Reduced Ejection Fraction When Compared to Patients With Heart Failure With Preserved Ejection Fraction

Introduction: Cardiac rehabilitation has been increasingly recognized as an integral part in the management of patients with congestive heart failure. It has been shown to improve the quality of life in this patient population. However, It is unknown how much cardiac rehabilitation reduces heart failure hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF) versus heart failure with preserved ejection fraction (HFpEF). Hypothesis: We hypothesize that outpatient cardiac rehabilitation is associated with reduced re-hospitalization for heart failure symptoms in patients with heart failure with HFrEF when compared with patients with HFpEF. Methods: We retrospectively analyzed data from 128 heart failure patients enrolled in an outpatient cardiac rehabilitation center from January 2015 to December 2020. The number of heart failure re-hospitalizations was measured in each of these patients. A Student t-test was used to analyze the difference between the two groups, while fisher’s test or chi square was used to analyze categorical variables. Results: Among the 128 patients enrolled in the outpatient cardiac rehabilitation center, age 68.1+-14 years, 63 (57.1%) were males. There were 70 patients (54.6%) in the HFrEF group and 58 (55.28%) in the HFpEF group. Hospitalization for acute exacerbation of heart failure symptoms was lower in the patients with HFrEF when compared with patients with HFpEF (41.3% vs 70.69% p value <0.0009). Conclusion: Outpatient cardiac rehabilitation program is associated with reduced hospitalization for heart failure symptoms in patients with HFrEF when compared to patients with HFpEF.

Abstract 14305: Diastolic Dysfunction and Activation of Ventricular and Atrial Unfolded Protein Response in a Novel Gottingen Miniswine Model of Heart Failure With Preserved Ejection Fraction

Introduction: During cardiac hypertrophy, the unfolded protein response (UPR) is activated which includes upregulation of chaperones to assist with protein folding and protein ubiquination for proteolytic degradation. We investigated the expression level of a key chaperone Hspa5 (heat shock protein A5) and ubiquinated protein levels in left ventricular (LV) and atrial (LA) tissue obtained from a preclinical porcine model heart failure with preserved ejection fraction (HFpEF) involving obesity and hypertension. Methods: Female Gottingen minipigs were fed standard or western diet (WD) for 20 weeks to induce obesity and metabolic syndrome and subsequent HFpEF. Those fed WD were also administered 11-deoxycorticosterone acetate (DOCA) (50 mg/kg, SQ) to induce hypertension. LV functional assessment was performed via transthoracic echocardiography and invasive hemodynamics at 20 weeks. In addition, UPR and proteasomal function were assayed following 20 weeks of HFpEF in ventricular and left atrial extracts via RT-qPCR and immunoblot. Results: Minipigs fed WD+DOCA demonstrated hypercholesterolemia, hypertension, LV hypertrophy and increased LVEDP. LVEF was >50% in HFpEF and control groups. We observed significant LV diastolic dysfunction as measured by E/e’ and LA dysfunction as decreased LA fractional area of change (LAFAC) at 20 weeks. LV extracts from HFpEF swine demonstrated a marked increase in Hspa5 without measurable increases in standard fetal genes (e.g. Myh7 ). LA extracts from HFpEF swine exhibited robust accumulation of ubiquitylated proteins compared to control swine. There was a positive correlation between Hspa5 and E/e’ ratio, and the inverse for LA ubiquitylated proteins and LA function. Conclusions: Coordinate with myocardial stiffening, hypertrophy and functional decline, HFpEF robustly augments proteostasis in both LV myocardium and LA recapitulating the clinical presentation of HFpEF patients.

Signs of heart failure with preserved ejection fraction in atrial fibrillation patients normalise in many patients after restoration of sinus rhythm

Abstract Background Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) coexist in many patients. AF and HFpEF are closely intertwined, but there are important knowledge gaps in the pathogenesis, risk, prevention and treatment of AF with concomitant HFpEF, in particular with respect to reversal of HFpEF signs. Purpose To assess the proportion of AF patients with (any) HFpEF criteria (including patients with heart failure with moderately reduced ejection fraction (HFmrEF)) who – after successful AF ablation – no longer meet the criteria for HFpEF on neurohumoral and echocardiographic level. Furthermore, to assess whether normalisation of HFpEF criteria positively affects AF recurrence. Methods Patients (n=526) underwent thoracoscopic AF ablation, consisting of pulmonary vein isolation (PVI) alone or PVI with additional lines in the case of persistent AF and were prospectively followed-up. Patients (n=338) with a left ventricular ejection fraction (LVEF) ≥40% and a successful ablation at 6 months follow-up, that is freedom of AF, or any atrial tachycardia of more than 30 seconds, were included in this study. Participants were grouped based on N-terminal pro-b type natriuretic peptide (NT-proBNP) into those with a NT-proBNP <125pg/ml, defined as control patients (group 1), and those with a NT-proBNP level ≥125pg/ml, defined as HFpEF patients (group 2). HFpEF patients were further classified in different degrees of HFpEF severity, based on the number of diagnostic echocardiographic criteria for diastolic dysfunction present into possible HFpEF (group 2a, <2 criteria), likely HFpEF (group 2b, 2 criteria) and definite HFpEF (2c, ≥3 criteria). The primary outcome was the change in HFpEF defining signs on neurohumoral (NT-proBNP) level and echocardiographic (number of echocardiographic criteria for diastolic dysfunction) level 6 months after restoration of sinus rhythm. Results In total, 69% of AF patients (with a preserved ejection fraction of ≥40%) fulfilled the criteria for HFpEF. In 23% of these patients, neurohumoral levels normalised after elimination of AF, and a normalisation of echocardiographic markers was seen in 58% of patients. Normalisation of HFpEF on a neurohumoral level was associated with numerically fewer AF recurrence at 1 year follow-up (23% versus 33% in patients with and without NT-proBNP <125 pg/ml respectively, p=0.212). This favourable outcome was not observed in patients with a normalisation of echocardiographic markers. Conclusion In AF patients with definite restoration of sinus rhythm HFpEF may be reversed. This suggests that neurohumoral and echographic changes are caused by AF rather than by HFpEF. Normalisation of neurohumoral changes after definite restoration of sinus rhythm led to better outcome with regards to AF-recurrence, which could be used in prediction of prognosis. Funding Acknowledgement Type of funding sources: None.

Validation of the HFA-PEFF and the H2FPEF scores for the diagnosis of heart failure with preserved ejection fraction in Japanese patients:a report from the Japanese multicentre registry

Abstract Background The standard diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF) is based on the following: 1) symptoms of HF, 2) preserved left ventricular (LV) ejection fraction (LVEF, >50%), and 3) presence of LV diastolic dysfunction confirmed by echocardiography or cardiac catheterisation. However, there are limits to the diagnostic accuracy of individual parameters, and what cut-off values should be applied and how they should be combined remain unclear. Diagnostic algorithms for HFpEF such as the HFA-PEFF algorithm and the H2FPEF score have been proposed; however, previous validation studies were conducted in stable chronic HF and did not include an invasive haemodynamic assessment. Thus, the diagnostic accuracy for HFpEF lacked robustness. Moreover, information on their applicability in the Asian population is limited. Purpose The aim of this study was to investigate these scores' diagnostic validity for HFpEF in Japanese patients recently hospitalised due to acute decompensated HF. Methods We examined patients with HFpEF recently hospitalised with acute decompensated HF whose HFA-PEFF and H2FPEF scores could be calculated at discharge from a nationwide HFpEF-specific multicentre registry (HFpEF group) and control patients who underwent echocardiography to investigate the cause of dyspnoea in our hospital (Non-HFpEF group). We calculated the HFA-PEFF and the H2FPEF scores among the studied population. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were computed to compare the diagnostic accuracy of these scores. Results The studied population included 372 consecutive patients (194 HFpEF group and 178 Non-HFpEF group; HFpEF prevalence, 52%). The HFA-PEFF score classified 155 (42%) of all patients into the high likelihood category (5–6 points) and only 19 (5%) into the low likelihood category (0–1 point). A high HFA-PEFF score could diagnose HFpEF with a high specificity of 84% and a positive predictive value (PPV) of 82%, and a low HFA-PEFF score could rule out HFpEF with a high sensitivity of 99% and a negative predictive value (NPV) of 89%. The H2FPEF score classified 86 (23%) of all patients into the high likelihood category (6–9 points) and 84 (23%) into the low likelihood category (0–1 point). HFpEF could be diagnosed with a high H2FPEF score (specificity, 97%; PPV, 94%) or ruled out with a low H2FPEF score (sensitivity, 97%; NPV, 93%). The diagnostic accuracy for the HFA-PEFF and H2FPEF scores was 0.82 (95% confidence interval [CI] 0.78–0.86) and 0.89 (95% CI 0.86–0.93), respectively, by the AUC of the ROC curve (P=0.004) (Figure 1A). In the HFA-PEFF sub-scores, the functional score showed little diagnostic value, while the morphological and biomarker scores showed moderate diagnostic value (Figure 1B). Conclusions The H2FPEF score may be more useful than the HFA-PEFF score in diagnosing HFpEF in Japanese patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS KAKENHI) Figure 1

Heart failure with preserved ejection fraction (HFpEF) pathophysiology study (IDENTIFY-HF): rise in arterial stiffness associates with HFpEF with increase in comorbidities

Abstract Background There has been a shift in paradigm proposing that comorbidities play a significant role towards the pathophysiology of the heart failure with preserved ejection fraction (HFpEF) syndrome. Further, HFpEF patients have abnormal macrovascular function, potentially contributing significantly in altered ventricular-vascular coupling in these patients. However, our full understanding of the role of comorbidities, arterial stiffness and it relationship with HFpEF remains incomplete. Purpose The IDENTIFY-HF study aims to shed light on the HFpEF pathophysiology and investigates whether gradually increase in arterial stiffness (in addition to ageing) due to increasing common comorbidities, such as hypertension and diabetes, is associated with HFpEF. Methods Arterial compliance was assessed in five groups (Groups A to E) matched for age, (≥70 years), sex and renal function: Group A; normal healthy volunteers without major comorbidities (control). Group B; patients with hypertension only. Group C; patients with hypertension and diabetes mellitus only. Group D; patients with HFpEF. Group E; patients with heart failure and reduced ejection fraction (HFrEF); the parallel group. Arterial compliance was assessed using pulse wave velocity (PWV), as the primary outcome measure and was compared between Group A to D. A separate comparison was made between Groups D and E. To avoid confounding factors, participants were asked to omit their morning blood pressure medication and abstain from caffeine for 12 hours prior to the study. Results From the 95 volunteers recruited, PWV was obtained in 94 subjects. The mean PWV in group A, B, C, D and E was 10.2-, 12.2-, 13.0-, 13.7- and 10.0 m/s respectively. After adjusting for covariance (age, sex, BMI and renal function), the mean difference between Group A (healthy volunteers) and D (HFpEF) was 2.14 m/s (p=0.023). Whilst the mean difference between the HFpEF and HFrEF group D and E respectively was 2.68 m/s (p=0.003). Conclusion Rise in comorbidities increases arterial stiffness, as measured by pulse wave velocity, which in turn significantly associates with HFpEF (p=0.023). It is therefore possible that the HFpEF syndrome may not be due to a primary cardiac pathology but rather an end-result of non-cardiac comorbidities affecting vascular resistance with perhaps some secondary cardiac involvement. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): 1)West Midlands Clinical Research Network, National Institute of Health Research, UK2)Research, Development & Innovation department of the University Hospitals Coventry & Warwickshire NHS Trust (RDI, UHCW), UK.

National prevalence and outcomes of coronary chronic total occlusion revascularization in patients with congestive heart failure

Abstract Background There is limited data on the prevalence and outcomes of coronary artery chronic total occlusion (CTO) revascularization in patients with congestive heart failure. Purpose Our goal is to study the prevalence and outcomes of CTO revascularization in terms of in-hospital mortality, re-admission rate, and complications in patients stratified by their heart failure status. Methods Patients with CTO who underwent percutaneous coronary intervention (PCI) were included for the years 2010 - 2018 from the national readmission database. We compared the national trends, prevalence and outcomes of CTO revascularization in patients with no heart failure, heart failure with preserved ejection fraction (HFpEF), and heart failure with reduced ejection fraction (HFrEF) using one-way ANOVA and logistic regression. Results A total of 166,244 (69±11 years, 26% women) patients with coronary CTO who underwent PCI were identified. Of these, 131,664 (79%) patients had no clinical diagnosis of HF, while 26,612 (16%) patients had HFpEF, and 7,968 (5%) patients had HFrEF. Majority of patients with HFpEF and HFrEF had a moderate to high Elixhauser comorbidity score, while those with no HF had mostly low to moderate score (p<0.001). We observed a steady decrease in annual CTO revascularization from a total of 24,708 in 2010 to 13,505 in 2018. However, the percentage of CTO revascularization in patients with HFrEF has increased during this period from 2% in 2010 to 8% in 2018. Interestingly, patients with HFpEF had higher rates of cardiac arrest (Odds Ratio (OR) 2.2; 95% Confidence Interval (CI) 1.8–2.7, p<0.001), ventricular tachycardia/fibrillation (OR 3.7; 95% CI 3.4–4.0, p<0.001), use of mechanical support (OR 5.5; 95% CI 4.9–6.2, p<0.001), and death during admission (OR 2.2; 95% CI 1.8–2.7, p<0.001) than those with no HF and with HFrEF. Similarly, patients with HFpEF had higher rates of intensive care unit admission (9%), than those with HFrEF (5%), and no HF (2%) (p<0.001). Readmission rates were similar across all three groups (0.5–0.7%, p=0.06). The median cost of hospitalization was significantly higher in the HFpEF group compared to the other groups ($98,366, p<0.001). Conclusion In this cohort of patients, we observed an overall annual decline in CTO revascularization over the 8-year study period. Despite this decline, we observed an increase in CTO revascularization in patient with HFrEF. Interestingly, patients with HFpEF had elevated in hospital mortality and higher rates of cardiac arrest, ventricular arrhythmias, mechanical circulatory support, and admission to the cardiac care unit than those with no HF, or those with HFrEF. Despite their persevered ejection fraction, our findings suggest that CTO revascularization in with patients with HFpEF carry a significant risk, thus risks versus benefits in this group of patients should be weighed considerably before attempting revascularization. Funding Acknowledgement Type of funding sources: None.

Heart failure with preserved ejection fraction after left-sided valve surgery: prevalent and relevant.

AimsTo investigate the epidemiological and prognostic relationship between heart failure with preserved ejection fraction (HFpEF) and left‐sided valve surgery using all‐cause mortality as a primary endpoint.Methods and resultsWe studied a total of 973 patients, of whom 673 had undergone left‐sided valve surgery (time from surgery to enrolment 50 ± 30 months after valve surgery) and 300 patients with HFpEF without prior surgery served as control group. Among patients after surgery, 67.4% fulfilled all criteria of HFpEF according to current guideline recommendations, 20.6% had no heart failure (HF), and 12.0% had HF with mid‐range or reduced ejection fraction (HFmrEF/HFrEF). During 83 ± 39 months of follow‐up, a total of 335 (34.4%) patients died. Compared to surgical patients with no subsequent HF, patients with HFpEF and HFmrEF/HFrEF after surgery showed significantly higher all‐cause mortality rates [hazard ratio (HR) 1.80, 95% confidence interval (CI) 1.25–2.57, P = 0.001; and HR 1.86, 95% CI 1.16–2.98, P = 0.010, respectively]. This increased mortality rate was similar to the control HFpEF group without surgery (HR 2.05, 95% CI 1.38–3.02, P < 0.001). Results remained consistent after adjustment for clinical and imaging risk factors and when using the established HFA‐PEFF risk score for HFpEF diagnosis. Notably, only 12.5% of HFpEF patients after surgery were diagnosed with HF despite regular follow‐up visits by board‐certified cardiologists. In contrast, 92.1% of HFmrEF/HFrEF patients after surgery were diagnosed correctly.ConclusionsHeart failure with preserved ejection fraction following left‐sided valve surgery is highly prevalent, associated with unfavourable outcomes, but rarely recognized.

Percutaneous edge-to-edge mitral valve repair for mitral regurgitation improves heart failure symptoms in heart failure with preserved ejection fraction patients.

AimsTherapeutic options for patients with heart failure with preserved ejection fraction (HFpEF) are sparse. Mitral regurgitation (MR) is a common feature of HFpEF and worsens heart failure symptoms and prognosis. Our study examines the outcome of patients with preserved left ventricular ejection fraction (LVEF) and elevated left atrial (LAP) or left ventricular filling pressures (LVEDP), indicative of HFpEF, after undergoing percutaneous edge‐to‐edge mitral valve repair (pMVR) for moderate–severe MR.Methods and resultsTwo hundred eleven patients with preserved LVEF (>50%), who underwent pMVR, were dichotomized by LAP (< / ≥15 mmHg) and LVEDP (< / ≥16 mmHg). Forty‐nine per cent of patients showed elevated LAP, and LVEDP was elevated in 55%, both indicating HFpEF. Patients with elevated filling pressures featured typical clinical characteristics of HFpEF, higher N‐terminal pro‐brain natriuretic peptide levels (5544.9 pg/mL in high LAP group vs. 3071.7 pg/mL in normal LAP group, P = 0.06; 5061.0 pg/mL in high LVEDP group vs. 3230.3 pg/mL in normal LVEDP group, P = 0.08), and higher prevalence of pulmonary hypertension (mean pulmonary artery pressure 36.4 mmHg in high LAP group vs. 26.3 mmHg in normal LAP group, P < 0.001; 35.2 mmHg in high LVEDP group vs. 29.7 mmHg in normal LVEDP group, P = 0.004) and atrial fibrillation (78.8% in normal LAP group vs. 61.0% in high LAP group, P = 0.04; 75.3% in high LVEDP group vs. 67.5% in normal LVEDP group, P = 0.25). Pre‐treatment MR grade and New York Heart Association (NYHA) class were similar in both normal filling pressure and HFpEF groups. pMVR in HFpEF patients achieved effective heart failure symptom relief comparable with patients with normal filling pressures: significant decrease of MR grade and NYHA class, as well as significant reduction of heart failure hospitalizations 12 months after compared with 12 months before MitraClip.ConclusionPercutaneous edge‐to‐edge mitral valve repair for moderate–severe MR is an effective treatment option for symptom relief in HFpEF patients.

Performance of the H2FPEF and the HFA-PEFF scores for the diagnosis of heart failure with preserved ejection fraction in Japanese patients: A report from the Japanese multicenter registry

BackgroundDiagnosing heart failure with preserved ejection fraction (HFpEF) is challenging. Although the H2FPEF score and HFA-PEFF algorithm have been proposed for diagnosing HFpEF, previous validation studies were conducted in stable chronic heart failure (HF). Moreover, information on their applicability in the Asian population is limited. We sought to investigate these scores' diagnostic performance for HFpEF in Japanese patients recently hospitalized due to acute decompensated HF. MethodsWe examined patients with HFpEF recently hospitalized with acute decompensated HF from a nationwide HFpEF-specific multicenter registry (HFpEF group) and control patients who underwent echocardiography to investigate the cause of dyspnea in our hospital (Non-HFpEF group). ResultsThe studied population included 372 patients (194 HFpEF group and 178 Non-HFpEF group; HFpEF prevalence, 52%). A high H2FPEF score (6–9 points) could diagnose HFpEF with a high specificity of 97% and a positive predictive value (PPV) of 94%, and a low H2FPEF score (0–1 point) could rule out HFpEF with a high sensitivity of 97% and a negative predictive value (NPV) of 93%. HFpEF could be diagnosed with a high HFA-PEFF score (5–6 points) (specificity, 84%; PPV, 82%) or ruled out with a low HFA-PEFF score (0–1 point) (sensitivity, 99%; NPV, 89%). The H2FPEF score was significantly superior to the HFA-PEFF score in diagnostic accuracy (area under the curve: 0.89 vs. 0.82, respectively, p = 0.004). ConclusionsThe H2FPEF and the HFA-PEFF scores had acceptable diagnostic accuracy in diagnosing HFpEF in Japanese patients.

Association of the classification and severity\xa0of heart failure with the incidence\xa0of contrast-induced acute kidney injury

Congestive heart failure (HF) is a known risk factor of contrast-induced acute kidney injury (CI-AKI). However, the relationship of the classification and severity of HF with CI-AKI remains under-explored. From January 2009 to April 2019, we recruited patients undergoing elective PCI who had complete pre- and post-operative creatinine data. According to the levels of ejection fraction (EF), HF was classified as HF with reduced EF (HFrEF) [EF < 40%], HF with mid-range EF (HFmrEF) [EF 40–49%] and HF with preserved EF (HFpEF) [EF ≥ 50%]. CI-AKI was defined as an increase of either 25% or 0.5 mg/dL (44.2 μmoI/L) in serum baseline creatinine level within 72 h following the administration of the contrast agent. A total of 3848 patients were included in the study; mean age 67 years old, 33.9% females, 48.1% with HF, and 16.9% with CI-AKI. In multivariate logistic regression analysis, HF was an independent risk factor for CI-AKI (OR 1.316, p value < 0.05). Among patients with HF, decreased levels of EF (OR 0.985, p value < 0.05) and elevated levels of N-terminal pro b-type natriuretic peptide (NT-proBNP) (OR 1.168, p value < 0.05) were risk factors for CI-AKI. These results were consistent in subgroup analysis. Patients with HFrEF were more likely to develop CI-AKI than those with HFmrEF or HFpEF (OR 0.852, p value = 0.031). Additionally, lower levels of EF were risk factors for CI-AKI in the HFrEF and HFmrEF groups, but not in the HFpEF group. NT-proBNP was an independent risk factor for CI-AKI in the HFrEF, HFmrEF and HFpEF groups. Elevated levels of NT-proBNP are independent risk factors for CI-AKI irrespective of the classification of HF. Lower levels of EF were risk factors for CI-AKI in the HFrEF and HFmrEF groups, but not in the HFpEF group.

Difference in Prognosis between Continuation and Discontinuation of A 5-Month Cardiac Rehabilitation Program in Outpatients with Heart Failure with Preserved Ejection Fraction.

Background: Cardiac rehabilitation (CR) is a requisite component of care for patients with heart failure (HF). We aimed to evaluate the clinical outcomes in outpatients with HF with preserved ejection fraction (HFpEF) compared to those in patients with non-HFpEF who did and did not continue a 5-month CR program. Methods: 173 outpatients with HF who participated in a 5-month CR program were registered. We divided them into two groups: HFpEF (n = 84, EF 63 ± 7%) and non-HFpEF (n = 89, EF 31 ± 11%). We further divided the patients into those who continued the CR program (continued group) and those who did not (discontinued group) in the HFpEF and non-HFpEF groups. The clinical outcomes at 5 months were compared among the groups. Results: There were no significant differences in patient characteristics at baseline between the continued and discontinued groups in the HFpEF and non-HFpEF groups except for % diabetes mellitus in the non-HFpEF group. The rates of all-cause death and hospital admissions in the continued group in both the HFpEF and non-HFpEF groups were significantly lower than those in the discontinued group. The all-cause death and hospital admissions in each group were independently associated with the continuation of the CR program. Conclusions: The continuation of a 5-month CR program was associated with the prevention of all-cause death and hospital admissions in both the HFpEF and non-HFpEF groups.

Left ventricular diastolic pressure gradient and outcome in advanced chronic kidney disease patients with preserved ejection fraction.

Assessment of left ventricular (LV) diastolic dysfunction is important in patients with chronic kidney disease (CKD). The early diastolic peak intraventricular pressure gradient (IVPG) has a vital role in diastolic function. Relative pressure imaging (RPI) is a new echocardiographic method to quantify IVPG. The purpose of this study was to analyze RPI-derived IVPG in advanced CKD patients with preserved LV ejection fraction. The study population consisted of 51 advanced CKD patients and 39 healthy controls. Patients were stratified by the evidence of heart failure with preserved ejection fraction (HFpEF) into HFpEF group (32 patients) and non-HFpEF group (19 patients). RPI analysis was used to determine the early diastolic LV relative pressure and pressure distribution. The total IVPG and segmental IVPGs corresponding to basal, mid, and apical part of the LV were calculated. Total IVPG, along with apical and mid IVPGs were all significantly reduced in HFpEF Group compared with non-HFpEF Group and controls (all P < 0.05). But no significant difference of total or segmental IVPGs was found between non-HFpEF Group and the controls. Additionally, apical IVPG < 0.02 mmHg/cm (Hazard ratio 9.82, 95 % confidence interval 2.01-48.01, P = 0.005) was the independent risk factor for the composite outcome (mortality and cardiovascular hospitalization) during a median follow-up of 24 months. Advanced CKD patients with HFpEF exhibited decreased apical and mid IVPG of the LV, and the severity of apical IVPG reduction correlated with poor outcome.

Prognostic value of pulmonary transit time by cardiac magnetic resonance in patients with heart failure with preserved ejection fraction

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): National Institute for Health Research Leicester Cardiovascular Biomedical Research Centre Background Quantifying pulmonary transit time (PTT) from cardiac magnetic resonance (CMR) first pass perfusion imaging is a novel technique for the evaluation of haemodynamic congestion in heart failure. Previous studies have demonstrated that PTT is prolonged in patients with heart failure with reduced ejection fraction (HFrEF) and that it provides independent prognostic information in this patient group. However, the potential diagnostic and prognostic roles of PTT assessment in patients with heart failure with preserved ejection fraction (HFpEF) remain to be established. Aim To compare PTT in healthy controls and in patients with HFpEF, and to determine the prognostic value of PTT in HFpEF. Methods In a prospective, observational study, HFpEF and age-matched control subjects underwent multi-parametric CMR at 3-Tesla, comprising quantitative left ventricular volumetric assessment using a standard steady-state free precession (SSFP) pulse sequence, and first-pass perfusion imaging at rest using a T1-weighted segmented inversion recovery gradient echo sequence (following injection of 0.04mmol/kg of contrast). PTT was calculated as the time interval between the peaks of signal intensity curves in the right and left ventricular blood pools (defined on the basal slice of the rest perfusion images). The primary endpoint was the composite of death or hospitalisation with heart failure. Results 88 HFpEF patients (age 73 ± 9 years, 51% male, EF 56.4 ± 5.6%) and 40 controls (age 73 ± 5 years, 43% male, EF 58.5 ± 4.7%) were studied. PTT was comparable in HFpEF patients (7.7 ± 3.8s) and in healthy controls (7.5 ± 1.8, p = 0.69). Normalised to cardiac cycle lengths, PTT remained comparable in HFpEF patients and healthy controls (8.5 ± 4.0 cardiac cycles versus 7.8 ± 1.6 cardiac cycles, respectively, p = 0.19). In the HFpEF group, during median follow-up of 3.4 years, there were 38 events (25 hospitalisations with heart failure, 13 deaths); a significant relationship between survival and PTT was not demonstrated (HR 1.06 [0.99,1.14] for a one-unit increase, p = 0.098). Conclusion In HFpEF, PTT is not prolonged compared with PTT in healthy subjects. Unlike in HFrEF, PTT does not appear to be diagnostically or prognostically significant in HFpEF. Figure 1: Graph showing signal intensity curves in the right (red) and left (green) ventricular blood pools Figure 2: Kaplan-Meier plot showing comparable rates of the composite endpoint in patients with PTT greater/less than median PTT (8 cardiac cycles)

Changes in clinical biochemical indexes of patients with heart failure with preserved ejection fraction or patients with hypertensive heart disease before and after treadmill exercise.

The incidence of hypertension is continuously increasing. This study aimed to investigate the changes in clinical biochemical indexes of patients with heart failure with preserved ejection fraction (HFpEF), or patients with hypertensive heart disease (HHD) before and after treadmill exercise. Seventy-eight patients with HFpEF and 78 patients with HHD who were admitted to our hospital between February 2020 and February 2021 were selected to take a treadmill exercise test. All patients continued to exercise for 1 month. Clinical biochemical indexes [hemoglobin A1c (HbA1c), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), total cholesterol (TC), N-segment pro-brain natriuretic peptide (NT-proBNP), and cardiac troponin I (cTnI)] were measured before and after the treadmill exercise test and compared between the two groups. Receiver operating characteristic (ROC) curves were drawn to analyze the optimal cutoff values of the clinical biochemical indexes in the diagnosis of HFpEF. The positive diagnostic rates of the biochemical indicators for HFpEF before and after treadmill exercise were compared using the optimal cut-off value of ROC as the positive standard. Before exercise, there was no significant difference in HbA1c, LDL-C, HDL-C, or TC between the two groups (P>0.05), but NT-proBNP and cTnI were significantly higher in the HFpEF group than in the HHD group (P<0.05). ROC curve analysis showed that before exercise, the best cutoff values for plasma NT-proBNP and cTnI in the diagnosis of HFpEF were 2,248.24 pg/mL and 1.14 ng/mL, respectively. After exercise, no significant difference was found in HbA1c, LDL-C, HDL-C, or TC between the two groups (P>0.05). However, the levels of NT-proBNP and cTnI in both groups were higher after exercise, with more significant increases seen in the HFPEF group (P<0.05). The positive rates of plasma NT-proBNP and cTnI in HFpEF group were statistically higher after exercise than before exercise (P<0.05). The changes in plasma NT-proBNP and cTnI in patient after treadmill exercise can be used as sensitive indicators for the diagnosis and differentiation of HFpEF and HHD.

223-OR: Heart Failure with Reduced, Midrange and Preserved Ejection Fraction in Chinese with Type 2 Diabetes: Risk Factors and Prognosis

Background: Diabetes predisposes to heart failure (HF). In a prospective cohort of Chinese with type 2 diabetes, we examined 1) clinical factors associated with incident HF, and 2) mortality post-HF, stratified by ejection fraction (EF). Methods: Between 1 Jun 1993 and 30 Jun 2015, 23348 patients with type 2 diabetes without history of HF were enrolled in the Hong Kong Diabetes Register, and followed for incident HF until 30 Jun 2017. HF subtypes were defined according to EF on echocardiogram: HF with reduced EF (HFrEF), EF &amp;lt;40%; HF with midrange EF (HFmrEF), EF 40-49%; HF with preserved EF (HFpEF), EF &amp;gt;=50%. Multivariate Cox regression was used to identify clinical factors associated with incident HF vs. no HF, by HF subtypes. 1-year and 5-year mortality rates were compared by HF subtypes. Results: Over a follow-up of 7.1 years from enrolment, 1195 patients developed HF, of whom 611 (51.1%) had an echocardiogram within 2 years of HF episode. Distribution of HF subtypes as follows: HFrEF 24.1%, HFmrEF 15.2%, HFpEF 60.7%. Old age, low GFR, albuminuria and history of coronary artery disease were associated with increased hazards for all HF subtypes. In addition, female sex, high BMI and history of neuropathy were associated with HFpEF, and low HDL cholesterol was associated with HFmrEF. Over a follow-up of 2.1 years post-HF, 760 patients (63.6%) died with a mortality rate of 189.4 per 1000 person-year. 1-year mortality rate was lower in HFpEF group (16.2%) than those with HFmrEF (vs. 26.9%, p=0.034) and HFrEF (vs. 31.3%, p&amp;lt;0.001). At 5 years, mortality rate in HFpEF group (45.6%) remained lower than those with HFmrEF (vs. 63.4%, p=0.008), but similar to HFrEF group (vs. 49.0%, p=0.199). Conclusions: HFpEF was the predominant HF subtype in Chinese with diabetes. Clinical factors predicting incident HF differed according to subtypes. 1-year mortality was lower in HFpEF group but mortality at 5 years were similar between HFpEF and HFrEF with a trend of higher mortality in HFmrEF group. Disclosure A. Luk: None. J. C. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, MSD Corporation, Sanofi, Other Relationship; Self; Asia Diabetes Foundation, GemVCare, Research Support; Self; Applied Therapeutics, AstraZeneca, Hua Medicine, Lilly Diabetes, Merck KGaA. X. Zhang: None. E. Fung: None. H. Wu: None. E. S. Lau: None. A. Yang: None. E. Chow: Research Support; Self; Medtronic, Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Sanofi-Aventis. A. P. Kong: Advisory Panel; Self; Lilly Diabetes, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Sanofi, Stock/Shareholder; Self; Aptorum. R. C. Ma: Other Relationship; Self; AstraZeneca, Medtronic, Research Support; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Tricida, Inc.

"Accelerated aging" of the heart as heart failure with preserved ejection fraction-analysis using leg-positive pressure stress echocardiography.

The aging process is a significant risk factor for heart failure. The incidence of heart failure with preserved ejection fraction (HFpEF) dramatically increases with age. Although HFpEF occurs along a continuum of aging of the cardiovascular system, the pathophysiology that differentiates overt HFpEF from physiological aging is not fully understood. A total of 102 subjects were prospectively recruited: 25 patients with HFpEF and 77 healthy controls. Controls were stratified into three age-groups: young (n = 27, 20-40years), middle aged (n = 25, 40-65years), and elderly (n = 25, > 65years). All participants underwent preload stress echocardiography using a leg-positive pressure (LPP) maneuver. With an increase in age, progressive concentric left ventricular (LV) remodeling was observed in healthy controls, resulting in the hemodynamic consequences of an age-dependent increase in the E/e' ratio (ANOVA, P < 0.001). During LPP stress, the E/e' ratio significantly increased in the middle-aged and elderly groups (from 8 ± 2 to 9 ± 3, from 10 ± 2 to 12 ± 3, P < 0.05, respectively), and this was more pronounced in patients with HFpEF (from 16 ± 5 to 17 ± 7, P < 0.05). Forward stroke volume (SV) significantly increased in each healthy group during LPP stress (all P < 0.001) but failed to increase in the HFpEF group (from 43 ± 13 to 44 ± 14mL/m2, P = 0.65). In a multivariate analysis, LV mass index (odds ratio [OR] 1.051, P < 0.05), E/e' ratio (OR 1.480; P < 0.05), and change in SV (OR 0.780; P < 0.05) were independent parameters that differentiated HFpEF from physiological aging. Structural remodeling and impaired preload reserve may both be critical features that characterize the pathophysiology of HFpEF.

Clinical Usefulness of the HFA-PEFF Diagnostic Scoring System in Identifying Late Elderly Heart Failure With Preserved Ejection Fraction Patients.

Diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging in elderly. This study investigated the diagnostic ability of the HFA-PEFF scoring system in elderly patients (>75 years of age). This study enrolled 286 subjects aged >75 years (130 men; mean [± SD] age 81.5±5.1 years): 95 healthy controls, 98 with hypertension (HT), and 93 with HFpEF. The HFA-PEFF score was calculated as a sum of points in functional, morphological, and biomarker domains. In the HFpEF group, 84%, 84%, and 70% of subjects met the major functional, morphological, and biomarker criteria for HFpEF, respectively. Thus, 73 subjects with HFpEF (78%) were diagnosed as having HFpEF using the HFA-PEFF scoring system. In contrast, among the healthy controls and subjects with HT, 52% and 72%, respectively, met the major functional criteria for HFpEF, 28% and 53%, respectively, met the morphological criteria, and 0% and 24%, respectively, met the biomarker criteria. As such, 32 subjects with HT (33%) were diagnosed with HFpEF. Even in the healthy control group, 72% were classified as having an intermediate probability of HFpEF, and 3 were diagnosed with HFpEF. In the late elderly, the HFA-PEFF scoring system diagnosed subjects with HFpEF precisely. In addition, this scoring system may be able to detect early stage HFpEF in the subclinical population.

Catheter ablation for non-paroxysmal atrial fibrillation accompanied by heart failure with preserved ejection fraction: feasibility and benefits in functions and B-type natriuretic peptide.

We aimed to examine the benefits of catheter ablation in patients with non-paroxysmal atrial fibrillation (AF) accompanied by heart failure (HF) with preserved ejection fraction (HFpEF), in comparison with the benefits in patients with AF accompanied by HF with reduced ejection fraction (HFrEF) or patients with no HF. From 1173 consecutive patients undergoing catheter ablation, 502 with non-paroxysmal AF were divided into three groups: no history of HF [plasma B-type natriuretic peptide (BNP) <100 pg/mL and no HF hospitalization; n = 125], HFpEF [left ventricular (LV) EF ≥50%; n = 293], and HF with midrange EF (HFmrEF) + HFrEF (LVEF <50%; n = 84) groups. The endpoints were AF recurrence at 1 year, changes in symptomatic and image-based functional status, and changes in BNP levels from baseline to 1 year. In the HFpEF group, AF recurred in 48 patients (16.4%) and 278 patients (94.8%) had sinus rhythm at 1 year; these values were comparable with those in the other groups. Significant improvement was observed in the left atrial diameter, LVEF, and New York Heart Association functional class in the HFpEF and HFmrEF + HFrEF groups. The BNP level significantly decreased irrespective of the index rate control status, and freedom from AF recurrence was an independent predictor of HF remission, defined as BNP <100 pg/mL at 1 year, in the HFpEF group. Catheter ablation is highly feasible for restoring sinus rhythm in non-paroxysmal AF with coexisting HFpEF, thereby improving cardiac function and BNP levels. Catheter ablation for AF may be an optional management strategy.

Impaired preload reserve is an important haemodynamic characteristics that discriminates between physiological ageing and overt heart failure with preserved ejection fraction

Abstract Funding Acknowledgements Type of funding sources: None. Background Ageing process per se is a major risk factor for heart failure (HF). In fact, the incidence of HF with preserved ejection fraction (HFpEF) dramatically increases with age. Although ageing plays a central role in the development of HFpEF, not all the elderly patients develop clinical HFpEF. Multiple abnormalities in the cardiovascular system have been proposed to contribute to the development of HFpEF. However, the pathophysiology that discriminates between physiological ageing and overt HFpEF is incompletely understood. Purpose The purpose of this study was to assess the effects of ageing on the cardiac structures and haemodynamics. Moreover, we evaluated the determinant factor that discriminates between physiological ageing and overt HFpEF by non-invasive preload increasing manoeuvre using leg-positive pressure (LPP) stress echocardiography. Methods A total of 91 subjects were prospectively recruited in this study: 22 patients with HFpEF and 69 healthy controls. Normal controls were further stratified into 3 age groups: young (n = 19, 20-40 years of age), middle-aged (N = 25, 40-65 years) and elderly (n = 25, &amp;gt;65 years). All subjects underwent LPP stress with a continuous external pressure of 90 mmHg around both lower limbs using dedicated airbags (Fig.). Results The left ventricular mass index (LVMI; young, 68 ± 19 g/m²; middle-age, 70 ± 18 g/m²; elderly, 84 ± 21 g/m²) and also the relative wall thickness (RWT; young, 0.34 ± 0.09; middle-age, 0.41 ± 0.06; elderly 0.55 ± 0.10) increased with ageing, which was accelerated in HFpEF (LVMI: 111 ± 32 g/m², RWT; 0.63 ± 0.19, ANOVA P &amp;lt; 0.001, respectively). Although baseline LV ejection fraction and cardiac output were quite comparable between groups, E/e’ ratio significantly increased with with ageing (ANOVA P &amp;lt; 0.001, Fig.). During LPP stress, E/e’ ratio significantly increased in the middle-aged and elderly groups (from 8.8 ± 2.7 to 9.7 ± 3.3, and from 11.4 ± 2.4 to 13.0 ± 2.2, P &amp;lt; 0.05, respectively), which was further deteriorated in HFpEF (from 16.8 ± 5.8 to 18.0 ± 7.6, P &amp;lt; 0.05). On the other hand, stroke volume index (SVi) significantly increased in each healthy group during LPP stress (young; from 45 ± 10 to 50 ± 11 mL/m², middle-age; from 39 ± 7 to 44 ± 6 mL/m² and elderly; from 37 ± 7 to 43 ± 8 mL/m², all P &amp;lt; 0.001), while SVi failed to increase in the HFpEF group (from 45 ± 13 to 45 ± 14 mL/m², P = 0.60). In a multivariate logistic regression analysis, LVMI (hazard ratio; HR 1.055, P &amp;lt; 0.05), baseline E/e’ (HR 1.444; P &amp;lt; 0.05), and ΔSVi (HR 0.755; P &amp;lt; 0.05) during LPP stress were the independent parameters that characterised overt HFpEF. Conclusions Striking parallels between structure-function alterations were observed in the physiological cardiovascular ageing process, which was further accelerated in patients with HFpEF. Not only structural remodeling and impaired diastolic function, but also impaired systolic reserve during preload stress is important haemodynamic feature that characterise the pathophysiology of HFpEF. Abstract Figure.

Left Atrial Ejection Force as a Marker for the Diagnosis of Heart Failure with Preserved Ejection Fraction.

Introduction:Several echocardiographic techniques are used to diagnose heart failure with preserved ejection fraction (HFPEF). Left atrial ejection force (LAEF) is a measure of left atrial (LA) systolic function. The aim of this study was to examine the use of LAEF as a measure for the diagnosis of HFPEF.Methods:A prospective study including 100 patients with HFPEF and 100 healthy controls. Heart failure association algorithm score for the diagnosis of HFPEF (HFA–PEFF score) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) were assessed. Transthoracic echocardiography measured indexed left ventricular mass index (LVMI), left ventricular (LV) ejection fraction, LA volume index (LAVI), global longitudinal strain (GLS), trans-mitral Doppler velocities, E/A ratio, E/e' ratio, and estimation of LAEF.Results:Patients in the HFPEF group were more frequently hypertensive, diabetic, and had a history of ischemic heart disease. NT-pro-BNP was higher in the HFPEF group (P < 0.0001). LVMI, relative wall thickness, and LAVI were all significantly higher in the HFpEF group (P < 0.0001 for all). LV-GLS was significantly lower in the HFPEF (P < 0.0001). LAEF was significantly higher in the study group 142.14 ± 24.27 versus 92.18% ±13.99% (P < 0.0001). A sub-group of 18 patients in the study group with a borderline HFA-PEF score of 4 had a LAEF that was significantly higher than the control group (P < 0.0001) but did not differ from the rest of the HFPEFF group patients.Conclusion:LAEF was significantly higher in patients with HFPEF compared to healthy controls. Patients with a borderline HFA-PEFF score of 4 had a significantly higher LAEF as compared to controls.