Diagnosis Of Heart Failure With Preserved Ejection Fraction Research Articles

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)

Management strategies in heart failure with preserved ejection fraction.

The diagnosis and therapy of heart failure with preserved ejection fraction (HFpEF) remain challenging. Currently, there are ongoing discussions on whether the diagnosis of HFpEF should be based solely on left ventricular ejection fraction, which may not account for the heterogeneity of HFpEF syndrome. This aspect has been addressed by the recently proposed HFA-PEFF and the H2FPEF algorithms, which take numerous diagnostic modalities into account to establish the diagnosis of HFpEF. Moreover, this review focuses on the adequate treatment of comorbidities and risk factors in HFpEF that should be an essential part of any HFpEF therapy. Furthermore, the management of fluid level in HFpEF patients is pointed out, as it plays an important role in symptom control. In addition, the value of LCZ696 therapy in HFpEF is discussed. Although LCZ696 had neutral effects in the large PARAGON-HF trial, it had previously been granted an extended indication by the Food and Drug Administration. Since the publication of the EMPEROR-Preserved trial, empagliflozin now represents the first drug to significantly improve the prognosis of HFpEF patients. Therefore, the role of SGLT2 inhibitors in HFpEF management is highlighted. Overall, this review aims to enhance the knowledge on the diagnostic processes and best treatments available for HFpEF patients.

New insights into the potential utility of the left atrial function analysis in heart failure with preserved ejection fraction diagnosis.

AimsNone of the conventional echocardiographic parameters alone predict increased NTproBNP level and symptoms, making diagnosis of heart failure with preserved ejection fraction (HFpEF) very difficult in some cases, in resting condition. We evaluated LA functions by 2D speckle tracking echocardiography (STE) on top of conventional parameters in HFpEF and preHF patients with diastolic dysfunction (DD), in order to establish the added value of the LA deformation parameters in the diagnosis of HFpEF.MethodsWe prospectively enrolled 125 patients, 88 with HFpEF (68±9 yrs), and 37 asymptomatic with similar risk factors with DD (preHF) (61±8 yrs). We evaluated them by NTproBNP, conventional DD parameters, and STE. Global longitudinal strain (GS) was added. LA reservoir (R), conduit (C), and pump function (CT) were assessed both by volumetric and STE. 2 reservoir strain (S) derived indices were also measured, stiffness (SI) and distensibility index (DI).ResultsLA R and CT functions were significantly reduced in HFpEF compared to preHF group (all p<0.001), whereas conduit was similarly in both groups. SI was increased, whereas DI was reduced in HFpEF group (p<0.001). By adding LA strain analysis, from all echocardiographic parameters, SR_CT<-1.66/s and DI<0.57 (AUC = 0.76, p<0.001) demonstrated the highest accuracy to identify HFpEF diagnosis. However, by multivariate logistic regression, the model that best identifies HFpEF included only SR_CT, GS and sPAP (R2 = 0.506, p<0.001). Moreover, SR_CT, DI, and sPAP registered significant correlation with NTproBNP level.ConclusionsBy adding LA functional analysis, we might improve the HFpEF diagnosis accuracy, compared to present guidelines. LA pump function is the only one able to differentiates preHF from HFpEF patients at rest. A value of SR_CT < -1.66/s outperformed conventional parameters from the scoring system, reservoir strain, and LA overload indices in HFpEF diagnosis. We suggest that LA function by STE could be incorporated in the current protocol for HFpEF diagnosis at rest as a major functional criterion, in order to improve diagnostic algorithm, and also in the follow-up of patients with risk factors and DD, as a prognostic marker. Future studies are needed to validate our findings.

Mimicking Metabolic Disturbance in Establishing Animal Models of Heart Failure With Preserved Ejection Fraction.

Heart failure (HF), the terminal state of different heart diseases, imposed a significant health care burden worldwide. It is the last battlefield in dealing with cardiovascular diseases. HF with preserved ejection fraction (HFpEF) is a type of HF in which the symptoms and signs of HF are mainly ascribed to diastolic dysfunction of left ventricle, whereas systolic function is normal or near-normal. Compared to HF with reduced ejection fraction (HFrEF), the diagnosis and treatment of HFpEF have made limited progress, partly due to the lack of suitable animal models for translational studies in the past. Given metabolic disturbance and inflammatory burden contribute to HFpEF pathogenesis, recent years have witnessed emerging studies focusing on construction of animal models with HFpEF phenotype by mimicking metabolic disorders. These models prefer to recapitulate the metabolic disorders and endothelial dysfunction, leading to the more detailed understanding of the entity. In this review, we summarize the currently available animal models of HFpEF with metabolic disorders, as well as their advantages and disadvantages as tools for translational studies.

Incremental diagnostic value of CMR-derived LA strain and strain rate in dialysis patients with HFpEF

ObjectivesTo test whether left atrial (LA) strain and strain rate add incremental value in the diagnosis of heart failure with preserved ejection fraction (HFpEF) in dialysis patients over clinical and conventional parameters only. BackgroundHFpEF frequently occurs in dialysis patients, however, the diagnosis of HFpEF is difficult. Although HFpEF is always companied with LA dysfunction, the performance of novel LA parameters, LA strain, and strain rate, in the diagnosis of HFpEF among dialysis patients remains unknown. MethodsIn the study, 153 dialysis patients (57 without HFpEF and 96 with HFpEF) and 52 healthy controls underwent cardiovascular magnetic imaging (CMR). Three components of LA strain and strain rate, including reservoir, contractile, and booster pump, were assessed via the CMR feature tracking module. Extra diagnostic value was examined by Harrell’s C-statistic. ResultsCompared with healthy controls and dialysis patients without HFpEF, dialysis patients with HFpEF had significantly impaired LA reservoir (εs) and contractile (εe) strain and strain rate (SRs, SRe), all p < 0.0001. Among these parameters, εs, εe, and SRe showed relatively high accuracy in diagnosing HFpEF among dialysis patients (areas under the curve: 0.84, 0.91, and 0.90, respectively). Reduction of εs, εe, and SRs provided incremental diagnostic value over conventional clinical and echocardiogram parameters. Combined with εs, εe or SRs, the diagnostic performance was further improved (Harrell’s C-statistic: 0.83 vs. 0.96, 0.97, and 0.97, respectively, all p < 0.0001). ConclusionsCMR-derived εs, εe, and SRs might add incremental diagnostic value over conventional indexes in diagnosing HFpEF among dialysis patients.

Analysis Of Clinical, Biochemical And Echocardiographic Criteria For Heart Failure With Preserved Ejection Fraction

Introduction Heart failure with preserved ejection fraction (HFpEF) is on pace to become the most common type of heart failure in the population with a prevalence that is increasing by 1% annually. Despite this, there remains no gold standard in diagnosing HFpEF. In addition to clinical exam and history, scoring criteria including H2FPEF score and HFA-PEFF score have been validated to assist in diagnosis. Guidelines and algorithms to determine echocardiographic diastolic dysfunction have also been described. Purpose Our study aimed to compare the sensitivities of various clinical, biochemical and echocardiographic criteria used to diagnosis HFpEF on a cohort of admitted HFpEF patients. Methods: This was a single-center retrospective review of inpatients with a primary diagnosis of HFpEF over a 2-year period. Electronic medical records were reviewed to analyze patient demographics, medical comorbidities and laboratory results. Echocardiograms were reviewed to analyze left ventricular mass, left atrial volume index and tricuspid regurgitation jet velocity as well as parameters of diastology to determine H2FPEF, HFA-PEFF scores, and American Society of Echocardiography diastolic dysfunction (ASE-DD) grading. Sensitivities for various diagnostic criteria were compared. A subgroup analysis was performed for different cut-offs of E/e’ septal velocities. Student's T test was performed for continuous data and statistical significant was defined as p<0.05. Results Over a 2 year period, 325 patients admitted with a primary diagnosis of HFpEF were analyzed. The average patient age was 80.2 years and 197 patients were female (60.6%). Brain natriuretic peptide (BNP) great than 100 pg/ml had the highest sensitivity of 94%. ASE-DD criteria for diastolic dysfunction had a sensitivity of 58%. H2FPEF risk percentage of ≥90% had sensitivity of 63%. Septal E/e’ of ≥15 had a sensitivity of 57% which increased to 90% when cut-off was lowered to ≥10. In a subgroup analysis of E/e’ <12 or ≥12, patients with E/e' ≥12 had significantly higher H2FPEF score, HFA-PEFF score and length of stay (p<0.05). Average E/e’ also had a positive correlation to percent change in BNP from baseline (R=0.83) and admission BNP (R=0.62). Conclusion Our study shows that current diagnostic criteria for HFpEF have relatively low sensitivity. Specifically, echocardiographic criteria may be too strict and a lower E/e’ cutoff may improve diagnostic sensitivity. The correlation of E/e’ and BNP suggests a relationship between the functional and biochemical entities of HFpEF. Further studies to optimize HFpEF diagnostic criteria are desired. Heart failure with preserved ejection fraction (HFpEF) is on pace to become the most common type of heart failure in the population with a prevalence that is increasing by 1% annually. Despite this, there remains no gold standard in diagnosing HFpEF. In addition to clinical exam and history, scoring criteria including H2FPEF score and HFA-PEFF score have been validated to assist in diagnosis. Guidelines and algorithms to determine echocardiographic diastolic dysfunction have also been described. Our study aimed to compare the sensitivities of various clinical, biochemical and echocardiographic criteria used to diagnosis HFpEF on a cohort of admitted HFpEF patients. Methods: This was a single-center retrospective review of inpatients with a primary diagnosis of HFpEF over a 2-year period. Electronic medical records were reviewed to analyze patient demographics, medical comorbidities and laboratory results. Echocardiograms were reviewed to analyze left ventricular mass, left atrial volume index and tricuspid regurgitation jet velocity as well as parameters of diastology to determine H2FPEF, HFA-PEFF scores, and American Society of Echocardiography diastolic dysfunction (ASE-DD) grading. Sensitivities for various diagnostic criteria were compared. A subgroup analysis was performed for different cut-offs of E/e’ septal velocities. Student's T test was performed for continuous data and statistical significant was defined as p<0.05. Over a 2 year period, 325 patients admitted with a primary diagnosis of HFpEF were analyzed. The average patient age was 80.2 years and 197 patients were female (60.6%). Brain natriuretic peptide (BNP) great than 100 pg/ml had the highest sensitivity of 94%. ASE-DD criteria for diastolic dysfunction had a sensitivity of 58%. H2FPEF risk percentage of ≥90% had sensitivity of 63%. Septal E/e’ of ≥15 had a sensitivity of 57% which increased to 90% when cut-off was lowered to ≥10. In a subgroup analysis of E/e’ <12 or ≥12, patients with E/e' ≥12 had significantly higher H2FPEF score, HFA-PEFF score and length of stay (p<0.05). Average E/e’ also had a positive correlation to percent change in BNP from baseline (R=0.83) and admission BNP (R=0.62). Our study shows that current diagnostic criteria for HFpEF have relatively low sensitivity. Specifically, echocardiographic criteria may be too strict and a lower E/e’ cutoff may improve diagnostic sensitivity. The correlation of E/e’ and BNP suggests a relationship between the functional and biochemical entities of HFpEF. Further studies to optimize HFpEF diagnostic criteria are desired.

IDF21-0515 Clinical characteristics of T2DM patients diagnosed with HFpEF: An Indian pilot survey

Background: Heart failure with preserved ejection fraction (HFpEF) represents a significant unmet medical need and is associated with poor outcomes. Registry evidence suggests a mortality-rate of 40.8% at 3 years, in Indian patients with HFpEF. Timely diagnosis of HFpEF in patients with predisposing factors and indicators, is essential in improving care. Aim: The clinical profile of patients with HFpEF, is known to be different in South-Asian patients, as compared to other Asian or global population. This is a real-world analysis of patients with T2DM and co-existing HFpEF, in the Indian diabetes outpatient-setting. Method: A cross-sectional analysis of patient-records was performed across 3 diabetes outpatient departments across the cities of Kolkata and Mumbai, in India. Records of patients with T2DM and HFpEF, as defined in the recent guidelines were included for analysis. Clinical characteristics of patients were descriptively analyzed. For categorical variables, unpaired t-test was used, whereas for non-parametric variables, odds ratio was estimated. Results: Records of 99 patients with HFpEF and T2DM, were available for analysis. The age ranged from 45 to 87 years, with average age being 66.3 (SD 9.3) years. 22% of patients were aged <60 years. 48% of patients were females. Of the 97 patients with available information for duration of diabetes, the average duration was 14.1 (SD 7.6) years. 26% patients had T2DM of <10 years’ duration. The average BMI was 26.7 (SD 4.8) kg/m2. 57% of patients were obese. 34% of females and 50% of males had a history of IHD. History of atrial fibrillation was present in 9% of patients. The average age of patients with and without A-Fib was 72.7 (SD 6.0) years, and 65.7 (SD 9.4) years, respectively; the difference in mean was significant (p = 0.034). Mean SBP was 140.5 (SD 19.0) mmHg. SBP level of ≥130 mmHg was observed in 76% of patients, and ≥140 mmHg was observed in 53.5% of patients. The average NT-proBNP LEVEL was 1235.4 pg/mL. The NT-proBNP levels ranged from 51 to 23000 pg/mL. 44 (47%) had eGFR level <60 mL/min/1.73m2. Average HbA1c level was 8.1% (SD 1.95%). 78% of patients had LDL-c level <100 mg/dL, whereas 46% had LDL-c level <70 mg/dL. Discussion: The analysis represents clinical characteristics of patients with HFpEF, in the clinical setting of T2DM in India. Despite HFpEF being strongly associated with old age, we observed at-least 1 in 5 patients to be <60 years old. Of note, 43% of patients with HFpEF were not obese. Blood-pressure control remained inadequate, despite good control of HbA1c and LDL-cholesterol levels. It is essential to suspect and screen for underlying HFpEF in patients having these comorbidities with T2DM, and to aggressively manage the risk-factors, keeping in mind the possible inconsistencies like younger-age or lower BMI in substantial number of patients.

Ensemble machine learning model identifies patients with HFpEF from matrix-related plasma biomarkers.

Arterial hypertension can lead to structural changes within the heart including left ventricular hypertrophy (LVH) and eventually heart failure with preserved ejection fraction (HFpEF). The initial diagnosis of HFpEF is costly and generally based on later stage remodeling; thus, improved predictive diagnostic tools offer potential clinical benefit. Recent work has shown predictive value of multibiomarker plasma panels for the classification of patients with LVH and HFpEF. We hypothesized that machine learning algorithms could substantially improve the predictive value of circulating plasma biomarkers by leveraging more sophisticated statistical approaches. In this work, we developed an ensemble classification algorithm for the diagnosis of HFpEF within a population of 480 individuals including patients with HFpEF, patients with LVH, and referent control patients. Algorithms showed strong diagnostic performance with receiver-operating-characteristic curve (ROC) areas of 0.92 for identifying patients with LVH and 0.90 for identifying patients with HFpEF using demographic information, plasma biomarkers related to extracellular matrix remodeling, and echocardiogram data. More impressively, the ensemble algorithm produced an ROC area of 0.88 for HFpEF diagnosis using only demographic and plasma panel data. Our findings demonstrate that machine learning-based classification algorithms show promise as a noninvasive diagnostic tool for HFpEF, while also suggesting priority biomarkers for future mechanistic studies to elucidate more specific regulatory roles.NEW & NOTEWORTHY Machine learning algorithms correctly classified patients with heart failure with preserved ejection fraction with over 90% area under receiver-operating-characteristic curves. Classifications using multidomain features (demographics and circulating biomarkers and echo-based ventricle metrics) proved more accurate than previous studies using single-domain features alone. Excitingly, HFpEF diagnoses were generally accurate even without echo-based measurements, demonstrating that such algorithms could provide an early screening tool using blood-based measurements before sophisticated imaging.

Impaired Right Atrial Reserve Function in Heart Failure with Preserved Ejection Fraction

Patients with heart failure with preserved ejection fraction (HFpEF) have multiple cardiac reserve limitations during exercise. However, no data are available regarding right atrial (RA) reserve capacity in HFpEF. The aim of this study was to determine the association of RA reserve impairments with right ventricular function and exercise capacity in HFpEF and to explore its diagnostic value. Patients with HFpEF (n=89) and control subjects without heart failure (n=108) underwent bicycle exercise echocardiography. RA reservoir, conduit, and booster pump strain at rest and during exercise were measured using speckle-tracking echocardiography. In a subset, simultaneous expired gas analysis was performed to measure peak oxygen consumption. At rest, RA reservoir strain was lower in patients with HFpEF than control subjects (27.0±17.1% vs 38.6±17.1%, P<.0001), while RA conduit and booster pump strain were similar between groups. During peak exercise, patients with HFpEF displayed marked reserve limitations in RA reservoir and booster pump function compared with control subjects, and the differences remained significant even after adjusting for confounding factors. During peak exercise, RA reservoir and booster pump strain were correlated with right ventricular systolic function. Lower RA booster pump strain during exercise was also weakly associated with lower cardiac output (r=0.34, P<.0001) and reduced peak oxygen consumption (r=0.47, P<.0001). RA reservoir strain during exercise had incremental diagnostic value to differentiate patients with HFpEF from control subjects over the established HFpEF diagnostic algorithms and left-sided strain parameters. Limitations in RA reservoir and booster pump function during exercise are present in patients with HFpEF, and the severity is associated with right ventricular systolic reserve, poor cardiac output, and depressed exercise capacity. Exercise RA strain assessment may help in the diagnosis of HFpEF.

Correlation between Atrial Fibrillation and Heart Failure with Preserved Ejection Fraction: A Review

Previous studies have demonstrated that patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) may develop the latter. The prevalence of 20-43% for AF in patients with HFpEF and prevalence of 50- 60% for HFpEF in AF patients. The pathophysiology indicates that AF usually precedes HFpEF, but each disease can promote the progression of the other one. Multiple mechanisms have been posited, such as left atrial (LA) fibrosis and myopathy as well as volume/pressure overload. Moreover, the combination of AF and HFpEF is associated with an increased rate of mortality as the presence of AF worsens the hemodynamics of HF. The diagnosis of HFpEF in patients with AF is underestimated, as the symptoms, laboratory values, and imaging techniques can be skewed by the presence of AF. Unfortunately, there are limited randomized controlled trials that recommend guideline-based treatments, such as choosing between rate and rhythm control. This narrative review aims to illustrate and summarize the pathophysiology, diagnosis, and treatment in the current literature for patients with AF and HFpEF.

A Novel Three-Dimensional and Tissue Doppler Echocardiographic Index for Diagnosing and Prognosticating Heart Failure With Preserved Ejection Fraction.

IntroductionThe diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. In this study, a novel echocardiography index based on three-dimensional and tissue Doppler echocardiography for diagnosing and estimating prognosis in HFpEF.Materials and MethodsPatients with symptoms and/or signs of heart failure and normal left ventricular ejection fraction (LVEF ≥50%) who underwent right heart catheterization were screened. Patients were divided based on pulmonary capillary wedge pressure (PCWP) of ≥15 mmHg and PCWP <15 mmHg. A diagnosis of HFpEF was confirmed by PCWP of ≥15 mmHg according to ESC guidelines. A novel index was calculated by the ratio between stroke volume standardized to body surface area (SVI) and tissue Doppler mitral annulus systolic peak velocity S' (SVI/S'). Its diagnostic and prognostic values were determined.ResultsA total of 104 patients (mean age 64 ± 12 years) were included. Of these, 63 had PCWP ≥15 mmHg and 41 patients had PCWP <15 mmHg. Compared to the PCWP <15 mmHg group, the ≥15 mmHg group had a significantly lower SVI/S' (P < 0.001). Logistic regression showed that SVI/S' was associated with high PCWP measured invasively. The SVI/S' had an area under the curve of 0.761 for diagnosing classifying between PCWP ≥15 mmHg and <15 mmHg. Kaplan–Meier analysis showed that the lower SVI/S' group showed a poorer prognosis.ConclusionsSVI/S' is a non-invasive index calculated by three-dimensional and tissue Doppler echocardiography. It is a surrogate measure of PCWP and can be used to diagnose and determine prognosis in HFpEF.