Diagnosis Of Heart Failure With Preserved Ejection Fraction Research Articles

Clonal Hematopoiesis in Clinical and Experimental Heart Failure With Preserved Ejection Fraction.

Clonal hematopoiesis (CH), which results from an array of nonmalignant driver gene mutations, can lead to altered immune cell function and chronic disease, and has been associated with worse outcomes in patients with heart failure (HF) with reduced ejection fraction. However, the role of CH in the prognosis of HF with preserved ejection fraction (HFpEF) has been understudied. This study aimed to characterize CH in patients with HFpEF and elucidate its causal role in a murine model. Using a panel of 20 candidate CH driver genes and a variant allele fraction cutoff of 0.5%, ultradeep error-corrected sequencing identified CH in a cohort of 81 patients with HFpEF (mean age, 71±6 years; ejection fraction, 63±5%) and 36 controls without a diagnosis of HFpEF (mean age, 74±7 years; ejection fraction, 61.5±8%). CH was also evaluated in a replication cohort of 59 individuals with HFpEF. Compared with controls, there was an enrichment of TET2-mediated CH in the HFpEF patient cohort (12% versus 0%, respectively; P=0.02). In the HFpEF cohort, patients with CH exhibited exacerbated diastolic dysfunction in terms of E/e' (14.9 versus 11.7, respectively; P=0.0096) and E/A (1.69 versus 0.89, respectively; P=0.0206) compared with those without CH. The association of CH with exacerbated diastolic dysfunction was corroborated in a validation cohort of individuals with HFpEF. In accordance, patients with HFpEF, an age ≥70 years, and CH exhibited worse prognosis in terms of 5-year cardiovascular-related hospitalization rate (hazard ratio, 5.06; P=0.042) compared with patients with HFpEF and an age ≥70 years without CH. To investigate the causal role of CH in HFpEF, nonconditioned mice underwent adoptive transfer with Tet2-wild-type or Tet2-deficient bone marrow and were subsequently subjected to a high-fat diet/L-NAME (Nω-nitro-l-arginine methyl ester) combination treatment to induce features of HFpEF. This model of Tet2-CH exacerbated cardiac hypertrophy by heart weight/tibia length and cardiomyocyte size, diastolic dysfunction by E/e' and left ventricular end-diastolic pressure, and cardiac fibrosis compared with the Tet2-wild-type condition. CH is associated with worse heart function and prognosis in patients with HFpEF, and a murine experimental model of Tet2-mediated CH displays greater features of HFpEF.

Identification of Subclinical Heart Failure With Preserved Ejection Fraction in Patients With Symptomatic Atrial Fibrillation

BackgroundAtrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) commonly coexist. We hypothesize that patients with symptomatic AF but without overt clinical HF commonly exhibit subclinical HFpEF according to established hemodynamic criteria. ObjectivesThe authors sought to use invasive hemodynamics to investigate the prevalence and implications of subclinical HFpEF in AF ablation patients. MethodsConsecutive symptomatic AF ablation patients were prospectively recruited. Diagnosis of subclinical HFpEF was undertaken by invasive assessment of left atrial pressure (LAP). Participants had HFpEF if the baseline mean LAP was >15 mm Hg and early HFpEF if the mean LAP was >15 mm Hg after a 500-mL fluid challenge. LA compliance was assessed invasively by monitoring the LAP and LA diameter during direct LA infusion of 15 mL/kg normal saline. LA compliance was calculated as Δ LA diameter/ΔLAP. LA cardiomyopathy was further studied with exercise echocardiography and electrophysiology study. Functional impact was evaluated using cardiopulmonary exercise testing and the AF Symptom Severity questionnaire. ResultsOf 120 participants, 57 (47.5%) had HFpEF, 31 (25.8%) had early HFpEF, and 32 (26.7%) had no HFpEF. Both HFpEF and early HFpEF were associated with lower LA compliance compared with those without HFpEF (P < 0.001). Participants with HFpEF and early HFpEF also displayed decreased LA emptying fraction (P = 0.004), decreased LA voltage (P = 0.001), decreased VO2peak (P < 0.001), and increased AF symptom burden (P = 0.002) compared with those without HFpEF. ConclusionsSubclinical HFpEF is common in AF ablation patients and is characterized by a LA cardiomyopathy, decreased cardiopulmonary reserve and increased symptom burden. The diagnosis of HFpEF may identify patients with AF with the potential to benefit from novel HFpEF therapies. (Characterising Left Atrial Function and Compliance in Atrial Fibrillation; ACTRN12620000639921)

Prevalence of Heart Failure With Preserved Ejection Fraction in Patients Undergoing Atrial Fibrillation Ablation Based on Resting and Post-Tachycardia Pacing Left Atrial Pressure

Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are frequent co-morbid conditions. In patients with symptomatic AF and preserved left ventricular ejection fraction the clinical diagnosis of HFpEF may be difficult, as history, examination, and echocardiography are not sensitive or specific. This study sought to assess the prevalence of HFpEF in patients undergoing AF ablation utilizing resting and post-tachycardia pacing left atrial pressure (LAP) measurements. This retrospective cohort study consisted of consecutive patients with symptomatic AF and preserved left ventricular ejection fraction who had invasive hemodynamic assessment (IHA) of LAP under resting and post-tachycardia pacing conditions while undergoing AF ablation from 2020 to 2022 at a tertiary care academic medical center. Elevated LAP was defined as ≥15 mm Hg at rest and ≥15 mm Hg post-tachycardia pacing. Patients were stratified into 3 groups: (1) normal resting and post-tachycardia pacing LAP (control group), (2) elevated resting LAP (apparent HFpEF), (3) normal resting but elevated post-tachycardia pacing LAP (occult HFpEF). A total of 78 patients were included with age 64.6 ± 9.1 years, 28 (36%) female, body mass index 33.3 ± 6.5 kg/m2, 5 (6%) paroxysmal and 73 (94%) persistent AF, and CHA2DS2-VASc 3.0 ± 1.5. IHA categorized 31 (40%), 32 (41%), and 15 patients (19%) into groups 1, 2, and 3 respectively. Notably, while only 9 patients (12%) were diagnosed with HFpEF based on clinical evaluation, 47 patients (60%) were diagnosed by IHA. IHA in patients undergoing AF ablation suggests a high prevalence of clinically undiagnosed HFpEF through a novel methodology measuring resting and post-tachycardia pacing LAP.

Regional expert opinion: Management of heart failure with preserved ejection fraction in the Middle East, North Africa and Turkey.

Although epidemiological data on heart failure (HF) with preserved ejection fraction (HFpEF) are scarce in the Middle East, North Africa and Turkey (MENAT) region, Lancet Global Burden of Disease estimated the prevalence of HF in the MENAT region in 2019 to be 0.78%, versus 0.71% globally. There is also a high incidence of HFpEF risk factors and co-morbidities in the region, including coronary artery disease, diabetes, obesity, hypertension, anaemia and chronic kidney disease. For instance, 14.5-16.2% of adults in the region reportedly have diabetes, versus 7.0% in Europe. Together with increasing life expectancy, this may contribute towards a higher burden of HFpEF in the region than currently reported. This paper aims to describe the epidemiology and burden of HFpEF in the MENAT region, including unique risk factors and co-morbidities. It highlights challenges with diagnosing HFpEF, such as the prioritization of HF with reduced ejection fraction (HFrEF), the specific profile of HFpEF patients in the region and barriers to effective management associated with the healthcare system. Guidance is given on the diagnosis, prevention and management of HFpEF, including the emerging role of sodium-glucose co-transporter-2 inhibitors. Given the high burden of HFpEF coupled with the fact that its prevalence is likely to be underestimated, healthcare professionals need to be alert to its signs and symptoms and to manage patients accordingly. Historically, HFpEF treatments have focused on managing co-morbidities and symptoms, but new agents are now available with proven effects on outcomes in patients with HFpEF.

Trimetazidine in heart failure with preserved ejection fraction: a randomized controlled cross-over trial.

Impaired myocardial energy homeostasis plays an import role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Left ventricular relaxation has a high energy demand, and left ventricular diastolic dysfunction has been related to impaired energy homeostasis. This study investigated whether trimetazidine, a fatty acid oxidation inhibitor, could improve myocardial energy homeostasis and consequently improve exercise haemodynamics in patients with HFpEF. The DoPING-HFpEF trial was a phase II single-centre, double-blind, placebo-controlled, randomized cross-over trial. Patients were randomized to trimetazidine treatment or placebo for 3months and switched after a 2-week wash-out period. The primary endpoint was change in pulmonary capillary wedge pressure, measured with right heart catheterization at multiple stages of bicycling exercise. Secondary endpoint was change in myocardial phosphocreatine/adenosine triphosphate, an index of the myocardial energy status, measured with phosphorus-31 magnetic resonance spectroscopy. The study included 25 patients (10/15 males/females; mean (standard deviation) age, 66 (10) years; body mass index, 29.8 (4.5) kg/m2 ); with the diagnosis of HFpEF confirmed with (exercise) right heart catheterization either before or during the trial. There was no effect of trimetazidine on the primary outcome pulmonary capillary wedge pressure at multiple levels of exercise (mean change 0 [95% confidence interval, 95% CI -2, 2] mmHg over multiple levels of exercise, P=0.60). Myocardial phosphocreatine/adenosine triphosphate in the trimetazidine arm was similar to placebo (1.08 [0.76, 1.76] vs. 1.30 [0.95, 1.86], P=0.08). There was no change by trimetazidine compared with placebo in the exploratory parameters: 6-min walking distance (mean change of -6 [95% CI -18, 7] m vs. -5 [95% CI -22, 22] m, respectively, P=0.93), N-terminal pro-B-type natriuretic peptide (5 (-156, 166) ng/L vs. -13 (-172, 147) ng/L, P=0.70), overall quality-of-life (KCCQ and EQ-5D-5L, P=0.78 and P=0.51, respectively), parameters for diastolic function measured with echocardiography and cardiac magnetic resonance, or metabolic parameters. Trimetazidine did not improve myocardial energy homeostasis and did not improve exercise haemodynamics in patients with HFpEF.

Developing a care pathway for heart failure with preserved ejection fraction: patient perceptions of existing care and their needs

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Scottish Government Background The Heart Disease Action Plan’s vision is that everyone in Scotland receives care that supports them in living well with their heart condition [1]. In 2021 NHS Ayrshire and Arran (NHS A&amp;A) was successful in attaining Scottish Government funding to develop and pilot a care pathway for those with heart failure with preserved ejection fraction (HFpEF). HFpEF is not widely understood by the wider healthcare community, and access to care for this population is limited. To help inform development of this pathway, a scoping exercise was undertaken to fully understand the needs of those with HFpEF, and to provide baseline data for evaluation of the new pathway. Purpose As part of the scoping exercise, patient interviews were conducted. The purpose of these was to establish patient perceptions of existing care for HFpEF and to ascertain how closely this aligned with their needs. Methods Five telephone interviews were conducted with individuals recently diagnosed and admitted to hospital with HFpEF within NHSA&amp;A. Interviews focused upon the following questions, with prompts on ‘what went well?’ and ‘what could have gone better?’: - What brought you to hospital? - How was your in-patient care? - What was the support like after discharge? - How is your current management of your medications? All interviews were conducted by the HFpEF Project Lead Nurse and took approximately 20-30 minutes. Results Care experience varied widely and three main themes were identified: support, communication, and continuity. Patients highlighted the importance of feeling listened to, and of having clear communication around the HFpEF diagnosis and care plan, with an appropriate channel available for them to ask questions and access relevant support. Continuity of care was dependent upon good multidisciplinary communication and integrated working, and upon staffing levels. There was a desire for ongoing clinical support for self- and medical management of their HFpEF at home. "No one is supporting....I manage myself" [someone] "…should contact you on discharge….[because]…you get an explanation in hospital but then there are questions that arise after discharge…." "I think they could have explained things better to me….just to have an opportunity to have questions answered and my heart condition discussed" "…I would say that there was a breakdown in the service [after discharge]." Conclusions The interviews demonstrate a clear need for a pathway for HFpEF that provides support, communication and continuity of care. It is hoped that evaluation of the pathway will demonstrate a positive impact upon these data.

Automated Echocardiographic Detection of Heart Failure With Preserved Ejection Fraction Using Artificial Intelligence

BackgroundDetection of heart failure with preserved ejection fraction (HFpEF) involves integration of multiple imaging and clinical features which are often discordant or indeterminate. ObjectivesThe authors applied artificial intelligence (AI) to analyze a single apical 4-chamber transthoracic echocardiogram video clip to detect HFpEF. MethodsA 3-dimensional convolutional neural network was developed and trained on apical 4-chamber video clips to classify patients with HFpEF (diagnosis of heart failure, ejection fraction ≥50%, and echocardiographic evidence of increased filling pressure; cases) vs without HFpEF (ejection fraction ≥50%, no diagnosis of heart failure, normal filling pressure; controls). Model outputs were classified as HFpEF, no HFpEF, or nondiagnostic (high uncertainty). Performance was assessed in an independent multisite data set and compared to previously validated clinical scores. ResultsTraining and validation included 2,971 cases and 3,785 controls (validation holdout, 16.8% patients), and demonstrated excellent discrimination (area under receiver-operating characteristic curve: 0.97 [95% CI: 0.96-0.97] and 0.95 [95% CI: 0.93-0.96] in training and validation, respectively). In independent testing (646 cases, 638 controls), 94 (7.3%) were nondiagnostic; sensitivity (87.8%; 95% CI: 84.5%-90.9%) and specificity (81.9%; 95% CI: 78.2%-85.6%) were maintained in clinically relevant subgroups, with high repeatability and reproducibility. Of 701 and 776 indeterminate outputs from the Heart Failure Association-Pretest Assessment, Echocardiographic and Natriuretic Peptide Score, Functional Testing (HFA-PEFF), and Final Etiology and Heavy, Hypertensive, Atrial Fibrillation, Pulmonary Hypertension, Elder, and Filling Pressure (H2FPEF) scores, the AI HFpEF model correctly reclassified 73.5% and 73.6%, respectively. During follow-up (median: 2.3 [IQR: 0.5-5.6] years), 444 (34.6%) patients died; mortality was higher in patients classified as HFpEF by AI (HR: 1.9 [95% CI: 1.5-2.4]). ConclusionsAn AI HFpEF model based on a single, routinely acquired echocardiographic video demonstrated excellent discrimination of patients with vs without HFpEF, more often than clinical scores, and identified patients with higher mortality.

Haemodynamic validation of the three-step HFA-PEFF algorithm to diagnose heart failure with preserved ejection fraction.

The HFA-PEFF algorithm (Heart Failure Association-Pre-test assessment, Echocardiography and natriuretic peptide score, Functional testing in cases of uncertainty, Final aetiology) is a three-step algorithm to diagnose heart failure with preserved ejection fraction (HFpEF). It provides a three-level likelihood of HFpEF: low (score<2), intermediate (score 2-4), or high (score>4). HFpEF may be confirmed in individuals with a score>4 (rule-in approach). The second step of the algorithm is based on echocardiographic features and natriuretic peptide levels. The third step implements diastolic stress echocardiography (DSE) for controversial diagnostic cases. We sought to validate the three-step HFA-PEFF algorithm against a haemodynamic diagnosis of HFpEF based on rest and exercise right heart catheterization (RHC). Seventy-three individuals with exertional dyspnoea underwent a full diagnostic work-up following the HFA-PEFF algorithm, including DSE and rest/exercise RHC. The association between the HFA-PEFF score and a haemodynamic diagnosis of HFpEF, as well as the diagnostic performance of the HFA-PEFF algorithm vs. RHC, was assessed. The diagnostic performance of left atrial (LA) strain<24.5% and LA strain/E/E'<3% was also assessed. The probability of HFpEF was low/intermediate/high in 8%/52%/40% of individuals at the second step of the HFA-PEFF algorithm and 8%/49%/43% at the third step. After RHC, 89% of patients were diagnosed as HFpEF and 11% as non-cardiac dyspnoea. The HFA-PEFF score resulted associated with the invasive haemodynamic diagnosis of HFpEF (P<0.001). Sensitivity and specificity of the HFA-PEFF score for the invasive haemodynamic diagnosis of HFpEF were 45% and 100% for the second step of the algorithm and 46% and 88% for the third step of the algorithm. Neither age, sex, body mass index, obesity, chronic obstructive pulmonary disease, or paroxysmal atrial fibrillation influenced the performance of the HFA-PEFF algorithm, as these characteristics were similarly distributed over the true positive, true negative, false positive, and false negative cases. Sensitivity of the second step of the HFA-PEFF score was non-significantly improved to 60% (P=0.08) by lowering the rule-in threshold to >3. LA strain alone had a sensitivity and specificity of 39% and 14% for haemodynamic HFpEF, increasing to 55% and 22% when corrected for E/E'. As compared with rest/exercise RHC, the HFA-PEFF score lacks sensitivity: Half of the patients were wrongly classified as non-cardiac dyspnoea after non-invasive tests, with a minimal impact of DSE in modifying HFpEF likelihood.

Association between allostatic load and adverse outcomes among older patients with heart failure with preserved ejection fraction

BackgroundThe allostatic load (AL) refers to the cumulative weakening of multiple physiological systems caused by repeated adaptation of the body to stressors There are still no studies have focused on the association between AL and the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). The present study aimed to investigate the association between AL and adverse outcomes, including mortality and HF admission, among elderly male patients with HFpEF.MethodsWe conducted a prospective cohort study of 1111 elderly male patients with HFpEF, diagnosed between 2015 and 2019 and followed up through 2021. We constructed an AL measure using a combination of 12 biomarkers. The diagnosis of HFpEF was made according to the 2021 European Society of Cardiology guidelines. A Cox proportional hazards model was used to determine the associations between AL and adverse outcomes.ResultsIn multivariate analysis, AL was significantly associated with increased risk of all-cause mortality (medium AL: adjusted hazard ratio [HR] = 2.53; 95% confidence interval [CI] 1.37–4.68; high AL: HR = 4.21; 95% CI 2.27–7.83; per-score increase: HR = 1.31; 95% CI 1.18–1.46), cardiovascular mortality (medium AL: HR = 2.67; 95% CI 1.07–6.68; high AL: HR = 3.13; 95% CI 1.23–7.97; per-score increase: HR = 1.20; 95% CI 1.03–1.40), non-cardiovascular mortality (medium AL: HR = 2.45; 95% CI 1.06–5.63; high AL: HR = 5.81; 95% CI 2.55–10.28; per-score increase: HR = 1.46; 95% CI 1.26–1.69), and HF admission (medium AL: HR = 2.68; 95% CI 1.43–5.01; high AL: HR = 3.24; 95% CI 1.69–6.23; per-score increase: HR = 1.24; 95% CI 1.11–1.39). Consistent results were found in multiple subgroup analyses.ConclusionsA higher AL was associated with poor prognosis in elderly men with HFpEF. AL relies on information that is easily obtained in physical examinations and laboratory parameters and can be assessed in various care and clinical settings to help risk stratification of HFpEF patients.

Evaluation the value of H2FPEF score and HFA-PEFF step E score in the diagnosis of heart failure with preserved ejection fraction

Background Clinical diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. The aim of the study is to evaluate the value of the H2FPEF score and HFA-PEFF step E score in the diagnosis of HFpEF. Methods 319 hospitalised patients with ‘shortness of breath’ or ‘dyspnoea’ were retrospectively collected and scored with the above two scores, respectively. They were divided into HFpEF group and non-HFpEF group in the study. Results Both the negative and positive predictive value of H2FPEF score and HFA-PEFF Step E score were 95.52%, 96.83% and 98.28%, 93.63%, respectively. However, there were 189 (59.25%) and 104 (32.60%) cases could not be diagnosed or excluded in the H2FPEF score and the HFA-PEFF step E score, respectively. Conclusions Both scores of the H2FPEF and the HFA-PEFF step E may be used to effectively rule out or confirm HFpEF according to the score point. However, there are three fifths and one third patients in the H2FPEF score and the HFA-PEFF step E score, respectively, in the intermediate scores who are needed further invasive catheterisation or exercise stress tests.

SEPTAL AND LEFT ATRIAL VOLUME INDEX AS PREDICTORS FOR HFPEF AMONGST TYPE 2 DIABETES MELLITUS PATIENTS

Objective: The aim of this study is to determine the prevalence and determination of risk factors of heart failure with preserved ejection fraction (HFpEF) diagnosed based on the consensus recommendation from the Heart Failure Association (HFA) and European Society of Cardiology (ESC) 2019 in type 2 diabetes mellitus (T2DM) patients in Malaysia. Design and method: We conducted a cross sectional study on patients with T2DM of more than 18 years old that were under Hospital UiTM follow-up from December 2021 until May 2021 (6 month). The participants were chosen via simple random sampling. Data's on demographic data, comorbid profile, symptoms and clinical examination including vitals sign, chemical profile and proceed with echocardiography and NTproBNP test to diagnosed HFpEF. Results: 201 diabetic patients were recruited and screened for HFpEF. 40 patients were confirmed with the diagnosis of HFpEF. Mean age was 61 ± 5.4 years. A significant difference in mean septal e’ was found between diabetic patients with HFpEF (5.5 ± 1.5 cm/s) and non-heart failure subjects (7.6 ± 1.0 cm/s)(p&lt;0.001, 95% CI -2.40,-1.49). There was also significant difference in mean left atrial volume index (LAVI) between diabetic patients with HFpEF (35.5 ± 1.5 ml/m2) and non-heart failure subjects (28.6 ± 1.0 ml/m2)(p&lt;0.001, 95% CI -2.50,-1.33). A stepwise increase in cortisol level corresponding to NTproBNP was observed(p&lt;0.061). Basal septal hypertrophy was seen in 30% of HFpEF diabetic patients (p&lt;0.081). Multiple linear regression analysis revealed septal e’ and LAVI as independent predictors of HFpEF in diabetic patients (r2 = 0.249, p&lt;0.001). Conclusions: One fifth of diabetic population had HFpEF and specific echocardiography parameters including septal e’ and LAVI were predictors for HFpEF. Emerging early imaging and chemical biomarkers for HFpEF such as basal septal hypertrophy and cortisol should be further studied.

Discovering HFpEF in symptomatic and asymptomatic elderly outpatients to prevent hospital admission.

Transthoracic echocardiography plays an important role as an imaging tool for the evaluation of heart failure with preserved ejection fraction (HFpEF). Among the imaging findings, the E/e' ratio, a surrogate for left atrial (LA) filling pressure, is a robust indicator that supports the diagnosis of HFpEF. Other findings such as left ventricular (LV) early diastolic tissue velocity (e'), LA volume, LA strain and LV global longitudinal strain are also related to LA filling pressure, and these parameters are useful for the diagnosis of HFpEF. Although some patients with HFpEF do not have abnormalities in these indices at rest, they may develop abnormalities in LA filling pressure exclusively during exercise.1 Therefore, HFpEF is difficult to diagnose in symptomatic elderly outpatients with limited exercise capacity (Figure 1). There are two types of probability tests in which HFpEF is present in patients with dyspnoea based on the findings obtained in clinical settings: the H2FPEF score2 and the HFA-PEFF score.3 Although both scores included echocardiographic indices, the H2FPEF score focuses on comorbidities, whereas the HFA-PEFF score includes natriuretic peptide levels. Most patients with HFpEF have a history of hypertension, and their blood pressure levels may no longer be elevated by medications at the time of evaluation.4 Furthermore, most patients with HFpEF show a high BMI, which is not the case in older patients.5 Because natriuretic peptide levels are occasionally within normal limits in patients with HFpEF, they may not be necessary for the diagnosis of HFpEF.2 Haemodynamic exercise tests play a key role when one cannot make a definitive decision of developing HFpEF. Noninvasive exercise testing does not discriminate between patients with cardiac and non-cardiac causes of dyspnoea.6 Although exercise echocardiography is a useful tool in place of invasive stress testing, there are contradictory results regarding the significance of the E/e' ratio for LA filling pressure.7, 8 Since LV diastolic function is affected by afterload, we recently evaluated LV diastolic function as a vascular resistance-integrated index: the ratio of LV diastolic elastance (Ed) to arterial elastance (Ea) = (E/e')/(0.9 × systolic blood pressure).9 This noninvasive index shows the ratio of LA filling pressure to LV end-systolic pressure and is a significant index of all-cause mortality in a multivariate Cox proportional hazards regression analysis performed by adjusting for age, comorbidities, natriuretic peptide levels and echocardiographic indices in elderly patients with HFpEF.10, 11 Stress tests cause an elevation of systolic blood pressure, and the extent of the change in blood pressure is different in each patient. Using an index such as Ed/Ea, the conflicting consequences described above may disappear. For the diagnosis of heart failure (HF), patients are aware of certain symptoms such as exertional dyspnoea, chest discomfort and fatigue. However, the symptoms are sometimes obscured in older patients. In clinical settings, it is important to identify patients with latent HFpEF who will likely be admitted for HF treatment in the near future. When populations with asymptomatic hypertension undergo invasive exercise stress or exercise echocardiography, some portions may exhibit an elevated LA filling pressure during exercise. We may call these populations ‘pre-HFpEF’ patients in terms of clinical entity.12 Asymptomatic LV hypertrophy is a potent risk factor for HFpEF.13 The main pathologies of HFpEF include cardiomyocyte remodelling and interstitial collagen deposition resulting from endothelial dysfunction and microvascular inflammatory changes.14-16 These latent populations might have treatment as ‘pre-HFpEF’ to avoid admission for HF. The diagnosis and treatment of asymptomatic elderly outpatients without a history of admission for HF, who possibly show exercise-induced elevation of LA filling pressure, remain to be defined. Recently, emerging differences in the phenotyping of HFpEF have been shown.17, 18 Asymptomatic patients with certain phenotypes must undergo stress echocardiography to diagnose pre-HFpEF. Under these conditions, the measurement of the Ed/Ea ratio may play a key role in the discrimination of several phenotypes in a multivariate model. As the medications and prognosis for HFpEF may be different from its phenotype,19, 20 it is urgent to elucidate the type of HFpEF or pre-HFpEF that should be medicated according to treatment type to reduce the incidence of admission for HF and mortality in the era of a super-ageing society. Among elderly clinic patients, we must detect symptomatic outpatients with possible HFpEF as well as asymptomatic ‘pre-HFpEF’ outpatients to reduce admission for HF in the near future and to conserve resources in the era of a super-ageing society. A vascular resistance-integrated LV diastolic index, (E/e')/(0.9 × systolic blood pressure), may play a role in revealing these patients in addition to possible comorbidities. None. No funding was received in relation to this article.

Heart failure with preserved ejection fraction (HFpEF): A missed diagnosis

One of the most common cause for “unexplained shortness of breath” is heart failure with preserved ejection fraction (HFpEF), that is frequently missed by the physician. Untill the wide use of BNP/NT ProBNP the term even remained unfamaliar to many of them. More over the concepts that, to make a diagnosis of HFpEF, a diastolic dysfunction is mandatory accounts for another cause of missing the diagnosis of HFpEF.The reality is Half of the all forms of heart failure is attributed to HFpEF. The diagnosis based on : the symptom of heart failure, the raised BNP/NT Pro BNP and any of the two of the either left venticular hypertrophy (LVH)/ left atrial enlargement (LAE) or features of diastolic dysfunction( as assessed by an echocadiography).The first criteria that is the symptom of heart failure is often non specific and frequently difficult to distinguish from other clinical conditions. The levels of BNP/NT ProBNP also needed to be defined according to various clinical conditions where there may be raised level of this biomarkers in the absence of heart failure.On the other hand the echocardiographic detection of LVH, LAE or left ventricular diastolic dysfunction is either time consuming or inconclusive in many patients. The various clinical phenotypes of HFpEF in the clinical back ground also make it diffcult to “fit one size for all”. Our presentation will focus on the various facets of missed diagnosed HFpEF. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 181-182

The association of cardiac troponin and cardiovascular events in patients with concomitant heart failure preserved ejection fraction and atrial fibrillation

BackgroundLimited data are available for risk stratification in patients with atrial fibrillation (AF) and combined heart failure with preserved ejection fraction (HFpEF). We aimed to explore the prognostic utility of high-sensitivity cardiac troponin I (hs-cTnI) in patients with newly detected AF and concomitant HFpEF.MethodsFrom August 2014 to December 2016, 2,361 patients with newly detected AF were polled in a retrospective single-center registry. Of which, 634 patients were eligible for HFpEF diagnosis (HFA-PEFF score ≥ 5) and 165 patients were excluded with exclusion criteria. Finally, 469 patients are classified into elevated or non-elevated hs-cTnI groups based on the 99th percentile upper reference limit (URL). The primary outcome was the incidence of major adverse cardiac and cerebrovascular events (MACCE) during follow-up.ResultsIn 469 patients, 295 were stratified into the non-elevated hs-cTnI group (< 99th percentile URL of hs-cTnI) and 174 were placed in the elevated hs-cTnI group (≥ 99th percentile URL of hs-cTnI). The median follow-up period was 24.2 (interquartile range, 7.5–38.6) months. During the follow-up period, 106 patients (22.6%) in the study population experienced MACCE. In a multivariable Cox regression model, the elevated hs-cTnI group had a higher incidence of MACCE (adjusted hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.08–2.55; p = 0.03) and coronary revascularization-caused readmission (adjusted HR, 3.86; 95% CI, 1.39–15.09; p = 0.02) compared with the non-elevated hs-cTnI group. The incidence of heart failure-caused readmission tended to occur more frequently in the elevated hs-cTnI group (8.5% versus 15.5%; adjusted HR, 1.52; 95% CI, 0.86–2.67; p = 0.08).ConclusionsOne-fifth of patients with AF and concomitant HFpEF experienced MACCE during follow-up, and elevated hs-cTnI was independently associated with higher risk of MACCE, as driven by heart failure and revascularization-caused readmission. This finding suggested that hs-cTnI may be a useful tool in individualized risk stratification of future cardiovascular events in patients with AF and concomitant HFpEF.

Exercise-induced B-lines for the diagnosis of heart failure with preserved ejection fraction: a two-centre study.

Diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging despite the use of scores/algorithms. This study intended to assess the diagnostic value of exercise lung ultrasound (LUS) for HFpEF diagnosis. We studied two independent case-control studies of HFpEF patients and control subjects undergoing different exercise protocols: (i) submaximal exercise stress echocardiography (ESE) with LUS performed by expert cardiologists (N = 116, HFpEF = 65.5%), and (ii) maximal cycle ergometer test (CET) (N = 54, HFpEF = 50%) with LUS performed by unexperienced physicians shortly trained for the study. B-line kinetics (i.e. peak values and their changes from rest) were assessed. In the ESE cohort, the C-index (95% CI) of peak B-lines for HFpEF diagnosis was 0.985 (0.968-1.000), whereas the C-index of rest and exercise HFA-PEFF scores (i.e. including stress echo findings) were < 0.90 (CI 0.823-0.949), and that of H2FPEF score was < 0.70 (CI 0.558-0.764). The C-index increase of peak B-lines on top of the above-mentioned scores was significant (C-index increase > 0.090 and P-value < 0.001 for all). Similar results were observed for change B-lines. Peak B-lines > 5 (sensitivity = 93.4%, specificity = 97.5%) and change B-lines > 3 (sensitivity = 94.7%, specificity = 87.5%) were the best cutoffs for HFpEF diagnosis. Adding peak or change B-lines on top of HFpEF scores and BNP significantly improved diagnostic accuracy. Peak B-lines showed a good diagnostic accuracy in the LUS beginner-led CET cohort (C-index = 0.713, 0.588-0.838). Exercise LUS showed excellent diagnostic value for HFpEF diagnosis regardless of different exercise protocols/level of expertise, with additive diagnostic accuracy on top of available scores and natriuretic peptides.

Combination of SVI/S' and diagnostic scores for heart failure with preserved ejection fraction.

The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains a challenge. There are three methods proposed as diagnostic tools. H2 FPEF score was determined by six weighted clinical characteristics and echocardiographic variables. Heart Failure Association (HFA)-PEFF algorithm consists of various functional and morphological variables as well as natriuretic peptides. SVI/S' is a novel echocardiographic parameter calculated by stroke volume index and mitral annulus systolic peak velocity. This study aimed to compare the three approaches in patients with suspected HFpEF. Patients referred to right heart catheterization for suspected HFpEF were classified into low-, intermediate- and high-likelihood groups according to H2 FPEF or HFA-PEFF scores. A diagnosis of HFpEF was confirmed by pulmonary capillary wedge pressure (PCWP) of ≥15 mm Hg according to the guidelines. In result, a total of 128 patients were included. Of these, 71 patients with PCWP ≥15 mm Hg and 57 patients with PCWP <15 mm Hg. Moderate correlations were observed between H2 FPEF score, HFA-PEFF score, SVI/S' and PCWP. The area under curve of SVI/S' was 0.82 for diagnosis of HFpEF, compared with 0.67 for H2 FPEF score and 0.75 for HFA-PEFF score by receiver-operating characteristics analysis. Combining SVI/S' with diagnostic scores showed higher Youden index and accuracy than each score alone. Kaplan-Meier analysis reported that the high-likelihood group showed poorer outcomes regardless the method used for diagnosis. Among the contemporary tools for identifying HFpEF in this study, the combination of SVI/S' with risk scores showed best diagnostic ability. Each of the strategies can determine rehospitalisation because of heart failure.

The HFA-PEFF diagnostic algorithm for diagnosing heart failure with preserved ejection fraction in hypertensive patients

The main causes of chronic heart failure (CHF) are hypertension (HTN) and coronary heart disease (CHD). One of the diagnostic methods for heart failure with preserved ejection fraction (HFpEF) can be the HFA-PEFF diagnostic algorithm, according to which diastolic stress test (DST) is indicated for patients with an intermediate probability of heart failure (HF). Objective. The aim of the study was to compare the incidence of HFpEF in patients with HTN with CHD and hypertensive patients without CHD by transthoracic echocardiogram using a DST according to the diagnostic algorithm HFA-PEFF. Design and methods. The study enrolled 45 patients with HTN and symptoms of HF who were divided into two groups according to the presence of CHD: patients with HTN and CHD (group I), patients with HTN without CHD (group II). The major and minor criteria of the HFA-PEFF diagnostic algorithm were evaluated to make the diagnosis of HFpEF. The DST was performed applying a passive leg raising test in patients with an intermediate probability of HFpEF. Results. According to the major and minor criteria of the HFA-PEFF: 7 (21,9 %) patients in group I and 3 (23,1 %) patients in group II did not have HFpEF. The confirmed HFpEF in group I was detected in 2 (6,2 %) patients, and none patients demonstrated confirmed HFpEF in group II. The remaining patients had an intermediate probability of HFpEF. DST with passive leg raising allowed to additionally diagnose HFpEF at an early stage in 6 (26,1 %) patients with HTN and CHD and in 1 (10 %) patient with HTN without CHD. Conclusions. The HFA-PEFF diagnostic algorithm using major and minor criteria allows to make the diagnosis of HFpEF in patients with HTN and symptoms of HF and, according to this algorithm in patients with HTN and CHD was detected more often, compared to patients with HTN without CHD.

Diagnostic value of reduced left atrial compliance during ergometry exercise in heart failure with preserved ejection fraction.

Diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging in patients presenting with chronic dyspnoea. We sought to determine the diagnostic value of reduced left atrial (LA) compliance during exercise to diagnose HFpEF. Ergometry exercise stress echocardiography was performed in 225 patients with HFpEF and 262 non-heart failure controls (non-cardiac dyspnoea [NCD]) in Protocol 1, where the diagnosis of HFpEF was defined by the HFA-PEFF algorithm. In Protocol 2, the diagnosis of HFpEF was ascertained by exercise right heart catheterization in 67 participants (49 HFpEF and 18 NCD). Speckle-tracking echocardiography was performed at rest and during exercise to determine LA compliance (ratio of LA reservoir strain to E/e'). As compared with NCD, patients with HFpEF demonstrated decreased LA reservoir strain and compliance at rest, and these differences further increased during exercise in Protocol 1. Exercise LA compliance discriminated HFpEF from NCD (area under the curve 0.87, p < 0.0001), with a superior diagnostic ability to exercise E/e' ratio (DeLong p = 0.005). Exercise LA compliance demonstrated incremental diagnostic value over clinical factors (age, systemic hypertension, and atrial fibrillation) and resting LA compliance (χ2 212.4 vs. 166.2, p < 0.0001). These findings were confirmed in Protocol 2. Left atrial compliance during exercise demonstrated superior diagnostic ability to exercise E/e' ratio, with incremental diagnostic value over the resting LA compliance. Exercise LA compliance may enhance the diagnosis of HFpEF among patients with dyspnoea.

MiR-181c targets Parkin and SMAD7 in human cardiac fibroblasts: Validation of differential microRNA expression in patients with diabetes and heart failure with preserved ejection fraction

BackgroundCardiac fibrosis represents a key element in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), a condition highly prevalent amongst geriatric patients, especially if diabetic. The microRNA 181c (miR-181c) has been shown to be associated with the response to exercise training in HFpEF patients and has been also linked to diabetic cardiovascular complications. However, the underlying mechanisms have not been fully elucidated. ObjectiveTo measure circulating miR-181c in elderly patients with HFpEF and diabetes mellitus (DM) and identify gene targets pathophysiologically relevant in HFpEF. MethodsWe quantified circulating miR-181c in frail older adults with a confirmed diagnosis of HFpEF and DM, and, as control, we enrolled age-matched subjects without HFpEF and without DM. We validated in human cardiac fibroblasts the molecular mechanisms linking miR-181c to a pro-fibrotic response. Results51 frail patients were included :34 patients with DM and HFpEF and 17 age-matched controls. We observed that miR-181c was significantly upregulated (p < 0.0001) in HFpEF patients vs controls. We confirmed in vitro that miR-181c is targeting PRKN and SMAD7. ConclusionsWe demonstrate that miR-181c levels are significantly increased in frail elderly adults with DM and HFpEF and that miR-181c targets PRKN and SMAD7 in human cardiac fibroblasts.

Heart Failure With Preserved Ejection Fraction: Current Status of Daily Clinical Practice in Indonesia.

Introduction Heart failure (HF)is a clinical syndrome with symptoms and/or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. Among HF types, HF with preserved ejection fraction (HFpEF) is the commonest form. However, the diagnosis and management of HFpEF are challenging. In addition, the perception of healthcare professionals (HCPs) towards the diagnosis and management of HFpEF patients differs due to the existing gap between the guidelines and daily clinical practice. Therefore, an online survey was conducted to understand the HCPs' knowledge and practice gaps in the diagnosis, treatment, and management of patients with HFpEF. Methods A total of 160 respondents, i.e., cardiologists, internists, and cardiology residents from different community-based practices and hospitals across Indonesia participated in an online continuing medical education (CME) survey. A questionnaire was formulated to assess awareness, current practice patterns, challenges, and confidence of the HCPs related to the HFpEF. Results HCPs stated that diagnosis of HF is the prime responsibility of cardiologists and general physicians but not of general internists. According to the HCPs, reduction in mortality, reduction in hospitalization, and improved quality of life are the most important goals of HF treatment. The perceived prevalence of HFpEFis estimated to be 30-60% and mortality rates of HFpEF and HF with reduced ejection fraction (HFrEF) are similar. Further, mixed types of responses with different combinations of diagnosis, treatment, and prevention, were obtained when HCPs were asked about the challenges faced in HFpEF. Among the therapies, angiotensin-converting enzyme (ACE) inhibitors, mineralocorticoid receptor antagonists (MRA), beta-blockers, and diuretics are frequently used for the treatment of HF. Conclusion The perception of the HCPs toward the diagnosis and management of HFpEF may affect optimal care. Based on ourfindings, the cardiologists are well aware of the current situation of HF in Indonesia and treat patients with HFpEF effectively.