Diagnosis Of Heart Failure With Preserved Ejection Fraction Research Articles

JS-HR-3: HEART DISEASE-FOCUS ON LEFT ATRIUM STRUCTURE-

Investigating potential biological relationships between heart failure (HF) with preserved ejection fraction (HFpEF) and associated diseases has been the focus of much research to establish personalized therapies. Hypertension is the most common concomitant disease in HFpEF patients, but the functional links between HFpEF and hypertension are still not fully understood and effective therapeutic strategies are still lacking. The structure of the left atrium (LA) is important for the diagnosis of HFpEF. In the SPRINT sub-analysis, intensive blood pressure control was not associated with ECG-defined LA abnormalities. In the ARGO-SIIA project, LA volumes indexed by height2 were more sensitive to subclinical hypertensive organ damage than those indexed by body surface area (BSA) in females. In the ARIC study, minimal LA volume index, but not standard assessment by maximum LA volume index, was associated with increased risk of incident HF or death regardless of measures of left ventricular function and NT-proBNP. In this presentation, the latest findings regarding the structure of the LA are updated and summarized in relation to HFpEF.

Central haemodynamic abnormalities and outcome in patients with unexplained dyspnoea.

Little data are available regarding prognostic implications of invasive exercise testing in heart failure with preserved ejection fraction (HFpEF). The present study aimed to investigate whether rest and exercise central haemodynamic abnormalities are associated with adverse clinical outcomes in patients with dyspnea. Patients with exertional dyspnoea and ejection fraction ≥50% (n=764) underwent invasive exercise testing and follow-up for heart failure hospitalization or death. There were 117 patients with events over a median follow-up of 2.7 (interquartile range 0.5-4.6)years. Among patients with normal resting pulmonary artery wedge pressure (PAWP) (<15 mmHg, n=380 [50%]), increased exercise PAWP (≥25 mmHg) was present in 187 (24% of cohort) and was associated with 2.4-fold higher risk of events compared to those with normal exercise PAWP (<25 mmHg, n=193 [25%]) (hazard ratio [HR] 2.44; 95% confidence interval [CI] 1.11-5.36; p=0.03), while patients with elevated resting PAWP (≥15 mmHg, n=384 [50%]) displayed even higher risk compared to HFpEF with normal resting PAWP (HR 2.24; 95% CI 1.38-3.65; p=0.001). Similar findings were observed for rest/exercise right atrial pressure, and rest/exercise pulmonary artery pressures. Higher peak oxygen consumption was associated with decreased risk of events, and this relationship was solely explained by exercise cardiac output. In a multivariable-adjusted Cox model, each 1 standard deviation (SD) increase in exercise PAWP was associated with a 41% greater hazard of events (HR 1.41; 95% CI 1.13-1.76; p=0.002), while each 1 SD decrease in exercise cardiac output was associated with a 37% increased risk (HR 0.63; 95% CI 0.47-0.83; p=0.001). Haemodynamic abnormalities currently used for diagnosis of HFpEF are associated with increased risk for adverse events. Treatments that reduce central pressures while improving cardiac output reserve may offer greatest benefit to improve outcomes in HFpEF.

Diagnostic Scores in Heart Failure with Preserved Ejection Fraction

The diagnosis of heart failure with preserved ejection fraction (HFpEF) can be challenging and diagnostic scores have been proposed to help in the diagnostic process. This article reviews these scores to provide insights on their role and interpretation in clinical practice. To date, two scores have been validated for the diagnosis of HFpEF. The H2FPEF includes clinical – obesity, hypertension, atrial fibrillation, age – and echocardiographic data – pulmonary hypertension and E/e’ ratio. The HFA-PEFF uses multiple echocardiographic parameters [...]

A simple guide to diagnose heart failure with preserved ejection fraction: A consensus recommendation from the Malaysian HFpEF Working Group (MY-HPWG)

Globally, prevalence of heart failure with preserved ejection fraction (HFpEF) has been increasing. Similar trend was observed in Asia. However, HFpEF diagnosis remained challenging especially in low-to-middle income Asian countries due to lack of access to diagnostic tools.

The Role of Multimodality Imaging in the Evaluation of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is highly prevalent, affecting approximately half of all patients with HF. The diagnosis of HFpEF can be notoriously challenging in clinical practice, given the many overlapping etiologies of dyspnea or reduced exercise tolerance in patients at risk for HFpEF. Multimodality imaging has an important role in establishing the diagnosis of HFpEF and the presence of elevated left ventricular filling pressures, identifying specific etiologies of HFpEF that can benefit from approved therapies, and discerning distinct phenogroups or mechanistic abnormalities that may inform the development of novel therapeutics.

Approach to Echocardiography in Heart Failure with Preserved Ejection Fraction.

As echocardiography is universally performed in the evaluation of suspected heart failure with preserved ejection fraction (HFpEF), a number of structural and functional characteristics relevant to both the diagnosis and phenotyping of HFpEF can be elucidated. Exclusion of alternate causes of heart failure is a critical first step performed principally by echocardiography. Once HFpEF is confirmed, echocardiography may provide insight into pathophysiology and phenotyping by quantifying atrial mechanics, pericardial restraint, degree of pulmonary hypertension, and atrial valvular regurgitation. Although current echo-Doppler assessment of filling pressures is insensitive to diagnose HFpEF, there are emerging technologies such as left atrial (LA) strain that hold promise for noninvasive diagnosis.

Texture analysis of native T1 images as a novel method for non-invasive assessment of heart failure with preserved ejection fraction in end-stage renal disease patients.

To explore the diagnostic potential of texture analysis applied to native T1 maps obtained from cardiac magnetic resonance (CMR) images for the assessment of heart failure with preserved ejection fraction (HFpEF) among patients with end-stage renal disease (ESRD). This study, conducted from June 2018 to November 2020, included 119 patients (35 on hemodialysis, 55 on peritoneal dialysis, and 29 with kidney transplants) in Renji Hospital. Native T1 maps were assessed with texture analysis, using a freely available software package, in participants who underwent cardiac MRI at 3.0 T. Four texture features, selected by dimension reduction specific to the diagnosis of HFpEF, were analyzed. Multivariate logistic regression was performed to examine the independent association between the selected features and HFpEF in ESRD patients. Seventy-six of 119 patients were diagnosed with HFpEF. Demographic, laboratory, cardiac MRI, and echocardiogram characteristics were compared between HFpEF and non-HFpEF groups. The four texture features that were analyzed showed statistically significant differences between groups. In multivariate analysis, age, left atrial volume index (LAVI), and sum average 4 (SA4) turned out to be independent predictors for HFpEF in ESRD patients. Combining the texture feature, SA4, with typical predictive factors resulted in higher C-index (0.923 vs. 0.898, p = 0.045) and a sensitivity and specificity of 79.2% and 95.2%, respectively. Texture analysis of T1 maps adds diagnostic value to typical clinical parameters for the assessment of heart failure with preserved ejection fraction in patients with end-stage renal disease. • Non-invasive assessment of HFpEF can help predict prognosis in ESRD patients and help them take timely preventative measures. • Texture analysis of native T1 maps adds diagnostic value to the typical clinical parameters for the assessment of HFpEF in patients with ESRD.

Catheter ablation in atrial fibrillation and heart failure with preserved ejection fraction improves peak pulmonary capillary wedge pressure, exercise capacity and quality of life: RCT STALL HFpEF

Abstract Introduction Atrial fibrillation (AF) frequently accompanies heart failure with preserved ejection fraction (HFpEF). AF exacerbates HFpEF through adverse haemodynamic effects. In turn, HFpEF promotes AF through adverse left atrial remodelling. Observational data suggest sinus rhythm restoration improves outcomes in patients with AF and HFpEF. However, there are no randomised data examining the effects of rhythm control with catheter-based AF ablation on HFpEF outcomes. Purpose To compare the effects of AF ablation versus usual medical therapy on markers of HFpEF severity, including exercise haemodynamics, natriuretic peptide levels and patient symptoms. Methods Patients with symptomatic AF and HFpEF underwent exercise right heart catheterization (RHC) and cardiopulmonary exercise testing (CPET). HFpEF diagnosis was based on left ventricular ejection fraction (LVEF) ≥50%, elevated natriuretic peptide and echocardiographic diastolic impairment. HFpEF was confirmed on exercise RHC based on peak exercise pulmonary capillary wedge pressure (PCWP) of ≥25mmHg. Patients were randomised to AF ablation versus medical therapy, with investigations repeated at 6 months. The primary outcome was change in PCWP on follow-up. Results 31 patients aged 66.1±7.5 years were randomized to AF ablation (16) versus medical therapy (15), with 51.6% female and 80.6% persistent AF. Baseline characteristics were comparable across groups. Paired analyses of ablation cohort showed significant reductions in peak PCWP (29.6±3.7 vs 25.9±4.6 mmHg, p&amp;lt;0.01), PCWP indexed for workload (39.0±57.9 vs 33.0±50.5 mmHg/W/kg, p&amp;lt;0.01), and BNP (146.2±80.5 vs 82.2±75.4 pg/mL, p=0.01); and increased resting cardiac output (4.6±0.9 vs 5.6±1.2 L/min, p=0.01), peak cardiac output (9.6±4.2 vs 10.4±3.7 L/min, p=0.02), peak (30s averaged) VO2 (1875.1±759.2 vs 2193.7±878.1 mL/min, p&amp;lt;0.01), peak absolute VO2 (1937.3±739.3 vs 2216.3±861.9 mL/min, p&amp;lt;0.01), peak (30s averaged) relative VO2 (19.4±5.9 vs 22.9±7.4 ml/kg/min) and peak workload (162.0±81.1 vs 184.4±83.4 W, p&amp;lt;0.01). Quality of life scores improved: AFEQT (45.3±20.9 vs 75±20.7, p&amp;lt;0.01) and MLHF (53±23.3 vs 17.5±22.8, p&amp;lt;0.01). Reversal of HFpEF by PCWP criteria occurred in 31.2% following AF ablation, and 50% among those free from arrhythmia recurrence. In the medical arm, there were no significant differences in RHC, CPET, and natriuretic peptide outcomes on follow-up versus baseline. Repeated measures mixed ANOVA testing showed significant time-randomisation interaction on peak VO2, absolute peak VO2, peak relative VO2, AFEQT/ MLHF scores, suggesting that significant improvements in these parameters were related to AF ablation. Conclusion In patients with concomitant AF and HFpEF, AF ablation improves invasive exercise haemodynamic parameters, increases exercise capacity, and enhances quality of life. Successful AF ablation may reverse the clinical syndrome of HFpEF in a subset of cases. Funding Acknowledgement Type of funding sources: None.

Value of the HFA-PEFF and H2FPEF scores in patients with heart failure and preserved ejection fraction caused by cardiac amyloidosis

Abstract Aims The HFA-PEFF and H2FPEF scores have been developed to diagnose heart failure with preserved ejection fraction (HFpEF), and hold prognostic value. Their use in patients with HFpEF caused by cardiac amyloidosis (CA) has never been investigated. Methods and results We evaluated the diagnostic and prognostic value of the HFA-PEFF and H2FPEF scores in 304 patients from 3 cohorts with HFpEF caused by transthyretin (ATTR)-CA (n=160, 53%) or immunoglobulin light-chain (AL)-CA (n=144, 47%). A diagnosis of HFpEF was more likely using the HFA-PEFF score with 2 (1%), 71 (23%), and 231 (76%) patients ranked as having a low (0–1), intermediate (2–4) or high (5–6) probability of HFpEF, respectively. Conversely, 36 (12%), 179 (59%) and 89 (29%) of patients ranked as having a low (0–1), intermediate (2–5) or high (6–9) probability of HFpEF using the H2FPEF score. During a median follow-up of 19 months (interquartile range 8–40), 132 (43%) patients died. The HFA-PEFF score, but not the H2FPEF, predicted a high risk of all-cause death which remained significant after adjustment for age, AL-CA diagnosis, high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, and echocardiographic parameters, including left ventricular (LV) global longitudinal strain, LV diastolic function and right ventricular function (hazard ratio 1.51, 95% confidence interval 1.16–1.95, p=0.002 for every 1-point increase in HFA-PEFF). Conclusions The HFA-PEFF score has a high sensitivity to diagnose HFpEF caused by CA and holds independent prognostic value for all-cause mortality, while the H2FPEF score does not. Funding Acknowledgement Type of funding sources: None.

Evaluation of the HFA-PEFF Score: results from the prospective DIAST-CHF cohort.

Although the number of patients suffering from heart failure with preserved ejection fraction (HFpEF) increases, the routine diagnosis remains a challenge. In the absence of a pathognomonic sign for HFpEF or specific treatment strategies, a prognosis-based characterization of suspected patients remains promising for both the risk stratification of the patients and a disease definition. The Heart Failure Association (HFA) of the European Society of Cardiology has introduced an algorithm with different levels of likelihood regarding the diagnosis of HFpEF, the HFA-PEFF score. We aimed to evaluate the predictive value of this algorithm in a large cohort regarding mortality, symptom burden, and the functional status. DIAST-CHF is a multicentre, population-based, prospective, observational study in subjects with at least one risk factor for HFpEF between the age of 50 and 85. We calculated the HFA-PEFF score (n=1668) and analysed the risk groups for overall mortality, cardiovascular hospitalization, and submaximal functional capacity (6-min walk distance) at baseline and after a follow-up period of 10years. Patients with high HFA-PEFF score values 5&6 showed a higher mortality than those with an intermediate score (score values 2-4) and low score values (high 21.3% vs. intermediate 10.1% vs. low 4.3%, P<0.001). Also, the burden of MACE (death, cardiovascular hospitalization, new myocardial infarction, first diagnosis of HF) was increased in the high score values group (high 40.7% vs. intermediate 25.9% vs. low 13.9%, P<0.001). Similarly, patients with higher scores had higher cumulative incidences of cardiovascular hospitalizations (P=0.011). Subjects with higher scores also had lower 6-min walk distance both at baseline and during follow-up. The HFA-PEFF score provides a reliable instrument to stratify suspected HFpEF patients by their risk for mortality, symptom burden, and functional status in cohort at risk with a follow-up period of 10years. As high HFA-PEFF scores are associated with worse outcome, the HFA-PEFF algorithm describes a defining approach towards HFpEF.

Left atrial strain in assessing heart failure with preserved ejection fraction in hypertensive patients

Aim. To compare the results of diagnosing heart failure with preserved ejection fraction (HFpEF) in patients with hypertension (HTN) according left atrial (LA) strain values with the results obtained using the H2FPEF score and diastolic stress testing (DST).Material and methods. The study included 293 patients with previously established HTN who were examined due to complaints of shortness of breath and/or palpitations (men, 97 (33,5%), mean age, 62,0 (55,0; 67,0) years). All patients underwent transthoracic echocardiography with the assessment of LA strain parameters and probability of HFpEF using the H2FPEF score. Eighty five patients with an intermediate probability of HFpEF underwent DST.Results. A low probability of HFpEF according to the H2FPEF score was registered in 35 (11,9%) patients, uncertain — in 206 (70,3%), high — in 52 (17,7%). DST was negative in 43 (50,6%) and positive in 42 (49,4%) patients with an intermediate probability of HFpEF. LA strain in the reservoir phase in patients with a low probability of HFpEF averaged (median and interquartile interval) 28,0 (23,6; 31,5)%, while in patients with an intermediate probability and negative DST — 24,0 (22,0; 26,8)%, with an intermediate probability and positive DST — 20,0 (18,0; 21,0)%, and with a high probability of HFpEF — 19,6 (16,9; 21,8)%. HFpEF was diagnosed in 94 patients, including 52 with a high probability on the H2FPEF score and 42 with an intermediate probability and positive DST. The diagnosis of HFpEF was ruled out in 78 patients, including 35 with a low probability on the H2FPEF score and 43 with an intermediate probability and negative DST. Further, 172 patients with confirmed or excluded HFpEF were randomly divided into two equal cohorts. In the training cohort, HFpEF was diagnosed in 44 (51,2%) patients, in the validation cohort — in 50 (58,1%). ROC analysis performed on the training cohort for the LA strain in reservoir phase showed AUC of 0,920 (95% confidence interval (CI), 0,842-0,968) and cut-off point of 21,5%. In the training cohort, the results of HFpEF diagnosis using the indicated criterion coincided with those using H2FPEF score and DST in 86,1% (95% CI, 77,2-91,8) of cases. The Cohen’s kappa was 0,721 (95% C,I 0,575-0,868). In the validation cohort, agreement was observed in 84,9% (95% CI 75,8-91,0) of cases with Cohen’s kappa of 0,702 (95% CI 0,553-0,851).Conclusion. In hypertensive patients, the diagnosis of HFpEF made on the basis of a decrease in the LA strain in reservoir phase to ≤21,5%, is in good agreement with the diagnosis made using the H2FPEF score and DST.

Value of the HFA-PEFF and H2 FPEF scores inpatients with heart failure and preserved ejection fraction caused by cardiac amyloidosis.

The HFA-PEFF and H2 FPEF scores have been developed to diagnose heart failure with preserved ejection fraction (HFpEF), and hold prognostic value. Their value in patients with HFpEF caused by cardiac amyloidosis (CA) has never been investigated. We evaluated the diagnostic and prognostic value of the HFA-PEFF and H2 FPEF scores in 304 patients from three cohorts with HFpEF caused by transthyretin CA (n=160, 53%) or immunoglobulin light-chain CA (n=144, 47%). A diagnosis of HFpEF was more likely using the HFA-PEFF score with 2 (1%), 71 (23%), and 231 (76%) patients ranked as having a low (0-1), intermediate (2-4), or high (5, 6) probability of HFpEF, respectively. Conversely, 36 (12%), 179 (59%) and 89 (29%) of patients ranked as having a low (0-1), intermediate (2-5), or high (6-9) probability of HFpEF using the H2 FPEF score. During a median follow-up of 19 months (interquartile range 8-40), 132 (43%) patients died. The HFA-PEFF score, but not the H2 FPEF score, predicted a high risk of all-cause death which remained significant after adjustment for age, AL-CA diagnosis, high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, and echocardiographic parameters, including left ventricular global longitudinal strain, left ventricular diastolic function and right ventricular function (hazard ratio 1.51, 95% confidence interval 1.16-1.95, p=0.002 for every 1-point increase in HFA-PEFF). The HFA-PEFF score has a higher diagnostic utility in HFpEF caused by CA and holds independent prognostic value for all-cause mortality, while the H2 FPEF score does not.

Modeling heart failure with preserved ejection fraction in rodents: Where do we stand?

Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by signs and symptoms of HF in the presence of a normal left ventricular systolic function. Over the past decade, HFpEF has become increasingly prevalent, accounting for greater than 50% of all clinical HF presentations. HFpEF is a complex disease with heterogeneous clinical presentations and multiple non-cardiac comorbidities, which frequently co-exist and contribute to its pathophysiology. To date, only a handful of therapies have been proven to improve, albeit marginally, the outcomes in HFpEF. The development of effective therapeutic agents is in part hampered by the lack of animal models that adequately recapitulate human HFpEF. Although numerous pre-clinical models developed over the years have been labeled as “HFpEF” specific, there has not been a consensus on the appropriate standards for pre-clinical HFpEF models. Thus, the extent to which they truly mirror human HFpEF cannot be systematically validated. Recently, a new algorithm (H2FPEF) was developed to standardize the clinical diagnosis of HFpEF. In this review, with the aid of the clinical H2FPEF scoring system, we evaluate the clinical applicability and translational values of various murine models of HFpEF.

Exercise testing in heart failure with preserved ejection fraction: an appraisal through diagnosis, pathophysiology and therapy-A clinical consensus statement of the Heart Failure Association and European Association of Preventive Cardiology of the European Society of Cardiology.

Patients with heart failure with preserved ejection fraction (HFpEF) universally complain of exercise intolerance and dyspnoea as key clinical correlates. Cardiac as well as extracardiac components play a role for the limited exercise capacity, including an impaired cardiac and peripheral vascular reserve, a limitation in mechanical ventilation and/or gas exchange with reduced pulmonary vascular reserve, skeletal muscle dysfunction and iron deficiency/anaemia. Although most of these components can be differentiated and quantified through gas exchange analysis by cardiopulmonary exercise testing (CPET), the information provided by objective measures of exercise performance has not been systematically considered in the recent algorithms/scores for HFpEF diagnosis, by neither European nor US groups. The current clinical consensus statement by the Heart Failure Association (HFA) and European Association of Preventive Cardiology (EAPC) of the European Society of Cardiology (ESC) aims at outlining the role of exercise testing and its pathophysiological, clinical and prognostic insights, addressing the implications of a thorough functional evaluation from the diagnostic algorithm to the pathophysiology and treatment perspectives of HFpEF. Along with these goals, we provide a specific analysis of the evidence that CPET is the standard for assessing, quantifying, and differentiating the origin of dyspnoea and exercise impairment and even more so when combined with echocardiography and/or invasive haemodynamic evaluation. This will lead to improved quality of diagnosis when applying the proposed scores and may also help to implement the progressive characterization of the specific HFpEF phenotypes, a critical step toward the delivery of phenotype‐specific treatments.

Diagnosis of Heart Failure With Preserved Ejection Fraction Among Patients With Unexplained Dyspnea

Diagnosis of heart failure with preserved ejection fraction (HFpEF) among dyspneic patients without overt congestion is challenging. Multiple diagnostic approaches have been proposed but are not well validated against the independent gold standard for HFpEF diagnosis of an elevated pulmonary capillary wedge pressure (PCWP) during exercise. To evaluate H2FPEF and HFA-PEFF scores and a PCWP/cardiac output (CO) slope of more than 2 mm Hg/L/min to diagnose HFpEF. This retrospective case-control study included patients with unexplained dyspnea from 6 centers in the US, the Netherlands, Denmark, and Australia from March 2016 to October 2020. Diagnosis of HFpEF (cases) was definitively ascertained by the presence of elevated PCWP during exertion; control individuals were those with normal rest and exercise hemodynamics. Logistic regression was used to evaluate the accuracy of HFA-PEFF and H2FPEF scores to discriminate patients with HFpEF from controls. Among 736 patients, 563 (76%) were diagnosed with HFpEF (mean [SD] age, 69 [11] years; 334 [59%] female) and 173 (24%) represented controls (mean [SD] age, 60 [15] years; 109 [63%] female). H2FPEF and HFA-PEFF scores discriminated patients with HFpEF from controls, but the H2FPEF score had greater area under the curve (0.845; 95% CI, 0.810-0.875) compared with the HFA-PEFF score (0.710; 95% CI, 0.659-0.756) (difference, -0.134; 95% CI, -0.177 to -0.094; P < .001). Specificity was robust for both scores, but sensitivity was poorer for HFA-PEFF, with a false-negative rate of 55% for low-probability scores compared with 25% using the H2FPEF score. Use of the PCWP/CO slope to redefine HFpEF rather than exercise PCWP reclassified 20% (117 of 583) of patients, but patients reclassified from HFpEF to control by this metric had clinical, echocardiographic, and hemodynamic features typical of HFpEF, including elevated resting PCWP in 66% (46 of 70) of reclassified patients. In this case-control study, despite requiring fewer data, the H2FPEF score had superior diagnostic performance compared with the HFA-PEFF score and PCWP/CO slope in the evaluation of unexplained dyspnea and HFpEF in the outpatient setting.

Critical Analysis and Limitations of the Diagnosis of Heart Failure with Preserved Ejection Fraction (HFpEF).

ResumoCom o aumento da expectativa de vida da população e a maior frequência de fatores de risco como obesidade, hipertensão arterial e diabetes, espera-se um aumento na prevalência de insuficiência cardíaca com fração de ejeção preservada (ICFEp). Entretanto, no momento, o diagnóstico e o tratamento de pacientes com ICFEp permanecem desafiadores. O diagnóstico sindrômico de ICFEp inclui diversas etiologias e doenças com tratamentos específicos, mas que apresentam pontos em comum em relação à apresentação clínica e à avaliação laboratorial no que diz respeito aos biomarcadores como BNP e NT-ProBNP, à avaliação ecocardiográfica do remodelamento cardíaco e às pressões de enchimento diastólico ventricular esquerdo. Extensos ensaios clínicos randomizados envolvendo a terapia nesta síndrome falharam na demonstração de benefícios para o paciente, fazendo-se necessária uma reflexão acerca do diagnóstico, dos mecanismos de morbidade, da taxa de mortalidade e da reversibilidade. Na revisão, serão abordados os conceitos atuais, as controvérsias e, especialmente, os desafios no diagnóstico da ICFEp através de uma análise crítica do escore da European Heart Failure Association.

Diagnosis of heart failure in the elderly: current status and future perspectives for echocardiographic diagnostic systems.

Since Japan is experiencing a super-aged society, the number of heart failure patients (HF) is increasing remarkably. In particular, the increase in heart failure with preserved ejection fraction (HFpEF), which is common in the elderly, has characterized the last decade. The diagnosis of HFpEF by assessment of left ventricular (LV) diastolic dysfunction, which is also referred to as diastolic heart failure, is an important role assigned to echocardiography. The Doppler echocardiographic algorithm for the evaluation of LV diastolic function from the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI) has been widely used to diagnose HFpEF. This article will focus on the HFpEF diagnostic algorithm proposed in 2018 by the Heart Failure Association of the European Society of Cardiology (HFA-PEFF score) based on autologous elderly cases. We compared the usefulness of the HFA-PEFF score with the ASE/EACVI algorithm. By comparing HFpEF patients with healthy elderly subjects and hypertensive patients with no history of HF, this paper will identify the usefulness and challenges of the HFA-PEFF score in the assessment of the elderly. The echocardiographic findings in at-risk or early-stage elderly patients with HFpEF will also be summarized. In addition, this review will describe future prospects for echocardiographic diagnostic systems for the prevention of HF onset and HF progression in the elderly and propose the concept of "early HFpEF".

In vivo imaging of heart failure with preserved ejection fraction by simultaneous monitoring of cardiac nitric oxide and glutathione using a three-channel fluorescent probe

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) remains unclear, making the diagnosis and treatment challenging. Cardiac oxidative and nitrative stress are strongly implicated in the pathogenesis of HFpEF. Herein, we present a unique three-channel fluorescent probe for evaluating cardiac oxidative and nitrative stress in HFpEF by simultaneous detection of NO and GSH. The probe exhibits a native green fluorescence (probe channel), while the presence of GSH and NO can sensitively turn the native green fluorescence into red fluorescence (GSH channel) and near-infrared fluorescence (NO channel), respectively. The probe clearly reveals that both GSH and NO levels are upregulated in cardiomyocytes and heart tissue with HFpEF. Moreover, it uncovers that the enhancement in NO and GSH levels are closely associated with increased level of iNOS (inducible nitric oxide synthase) and activation of the Keap1 (Kelch-like ECH-associated protein 1)/Nrf2 (nuclear factor erythroid 2–related factor 2)/ARE (antioxidant response element) signaling pathway in cardiomyocytes, respectively. This work proposes a promising approach for distinguishing normal heart and HFpEF heart by in vivo noninvasive imaging of both GSH and NO, and greatly contributing to the improvement of the diagnosis and treatment of HFpEF.

Biomarkers in Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous disorder developing from multiple aetiologies with overlapping pathophysiological mechanisms. HFpEF diagnosis may be challenging, as neither cardiac imaging nor physical examination are sensitive in this situation. Here, we review biomarkers of HFpEF, of which the best supported are related to myocardial stretch and injury, including natriuretic peptides and cardiac troponins. An overview of biomarkers of inflammation, extracellular matrix derangements and fibrosis, senescence, vascular dysfunction, anaemia/iron deficiency and obesity is also provided. Finally, novel biomarkers from -omics technologies, including plasma metabolites and circulating microRNAs, are outlined briefly. A cardiac-centred approach to HFpEF diagnosis using natriuretic peptides seems reasonable at present in clinical practice. A holistic approach including biomarkers that provide information on the non-cardiac components of the HFpEF syndrome may enrich our understanding of the disease and may be useful in classifying HFpEF phenotypes or endotypes that may guide patient selection in HFpEF trials.

0716 Risk for Heart Failure with preserved Ejection Fraction in patients with or without Obstructive Sleep Apnea

Abstract Introduction Approximately two out of three patients with Heart Failure with preserved Ejection Fraction (HFpEF) have co-morbid sleep apnea, but the risk of HFpEF in patients who test positive for obstructive sleep apnea (OSA) is unknown. Methods Referred subjects (n=228) over the age of 18 underwent a diagnostic in-lab polysomnogram at the University of Michigan Sleep Laboratories between 1/8/2019-3/11/2020 and an echocardiogram within 12 months of their sleep study. Individuals with a known history of HFpEF were excluded (n=44). OSA was defined as an apnea-hypopnea-index (AHI) ≥ 5/hour. Clinical and echocardiogram variables were abstracted from the electronic medical record and used to determine H2FPEF scores (ordinal scale, range 0-9). The H2FPEF score is a validated predictor of HFpEF risk in patients with dyspnea. In the presence of dyspnea, a H2FPEF score ≥ 3 indicates a &amp;gt;50% risk of HFpEF, though dyspnea was not assessed in this study. HFpEF probability (continuous variable) was determined using the corresponding online calculator. Linear regression was used to predict HFpEF probability based on AHI. Results The 184 subjects without a known diagnosis of HFpEF had a median age of 65 years (interquartile range (IQR) 51, 71). Seventy subjects (38%) were male, 150 (82%) had OSA, and the median AHI was 15 (7, 35). The median H2FPEF score was 3 (2, 5). Among 34 participants without OSA, 10 (29%) had an H2FPEF score ≥ 3, whereas among 150 participants with OSA, 59 (39%) had an H2FPEF score ≥ 3. Linear regression indicated that higher AHI is associated with a higher probability of HFpEF (β = 0.39, p=0.0001). Conclusion Many patients referred for polysomnography may be at high risk for HFpEF. Sleep-study-referred subjects without clinically-indicated echocardiograms were not assessed, but patients at sleep disorders centers who test positive for OSA may have a particularly high rate of undiagnosed HFpEF. Sleep physicians should consider a cardiology referral in appropriately screened patients. Support (If Any)