Diagnosis Of Heart Failure With Preserved Ejection Fraction Research Articles

The value of speckle-tracking stratified strain combined with myocardial work measurement in evaluating left ventricular function in patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent progressive disease accompanied by poor quality of life, high utilization of medical resources, morbidity, and mortality. However, the role of left ventricular (LV) systolic dysfunction has yet to be well elaborated despite the preservation of the LV ejection fraction. This study aimed to explore the diagnostic value of speckle-tracking stratified strain combined with myocardial work (MW) measurement in evaluating LV systolic dysfunction in patients with HFpEF. A total of 125 study consecutive individuals, 64 HFpEF patients, and 61 controls were prospectively enrolled in the Fourth Affiliated Hospital of Harbin Medical University. In addition to the conventional echocardiographic parameters, LV stratified strain and MW parameters were statistically compared between the HFpEF and control groups. The global longitudinal strain (GLS) of the subendocardium, myocardium, and subepicardium (GLSendo, GLSmyo, and GLSepi); the transmural gradient (ΔGLS); the global myocardial work index (GWI), global myocardial work efficiency (GWE), global myocardial constructive work (GCW), and the global myocardial wasted work (GWW) were included. Area under the receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of these univariate and multivariable logistic models in detecting impaired LV systolic function in HFpEF. Ten-fold cross-validation was used to evaluate the generalizability of the predictive model. Stratified strains values showed a gradient decline from GLSendo to GLSepi in both control and HFpEF patients. Compared with the control group, HFpEF patients had a significantly reduced GLSepi, GLSmyo, GLSendo, ΔGLS, GWI, GWE, and GCW and a significantly increased GWW (all P<0.001). In the derivation set, the optimal logistic model (combined stratified strain and MW variables) demonstrated the highest performance in predicting LV systolic function impairment in HFpEF patients. The best-performing model with a mean area under the curve (AUC) of 0.966 [95% confidence interval (CI): 0.88 to 1] accessed by 10-fold cross-validation. In the validation set, the AUC of the optimal logistic model was 0.933 (95% CI: 0.85 to 1), the sensitivity was 87%, and the specificity was 93%. Both speck-tracking stratified strain and MW measurement may sensitively detect impairment of LV myocardial function at an early stage for patients with HFpEF. Combining the two techniques may improve the quality of HFpEF diagnosis and may provide a reference value for the early diagnosis of HFpEF in the future.

Heart Failure with Preserved Ejection Fraction: How to Deal with This Chameleon.

Heart failure with preserved ejection fraction (HFpEF) is characterized by a notable heterogeneity in both phenotypic and pathophysiological features, with a growing incidence due to the increase in median age and comorbidities such as obesity, arterial hypertension, and cardiometabolic disease. In recent decades, the development of new pharmacological and non-pharmacological options has significantly impacted outcomes, improving clinical status and reducing mortality. Moreover, a more personalized and accurate therapeutic management has been demonstrated to enhance the quality of life, diminish hospitalizations, and improve overall survival. Therefore, assessing the peculiarities of patients with HFpEF is crucial in order to obtain a better understanding of this disorder. Importantly, comorbidities have been shown to influence symptoms and prognosis, and, consequently, they should be carefully addressed. In this sense, it is mandatory to join forces with a multidisciplinary team in order to achieve high-quality care. However, HFpEF remains largely under-recognized and under-treated in clinical practice, and the diagnostic and therapeutic management of these patients remains challenging. The aim of this paper is to articulate a pragmatic approach for patients with HFpEF focusing on the etiology, diagnosis, and treatment of HFpEF.

Revascularization for Patients With Heart Failure With Preserved Ejection Fraction and Coronary Artery Disease

Coronary artery disease (CAD) is one of the main causes of heart failure (HF) with preserved ejection fraction (HFpEF). The efficacy of revascularization therapy in patients with HFpEF and CAD, however, remains unclear. Patients who underwent coronary angiography from January 2017 to December 2019 were included in this retrospective study if they further satisfied the diagnosis of HFpEF (left ventricular ejection fraction ≥50% plus plasma N-terminal pro-BNP ≥125pg/ml) and CAD (patients had a history of confirmed myocardial infarction or ≥50% stenosis in at least 1 epicardial coronary vessel). Clinical data, way of revascularization, and outcome events (unplanned repeated revascularization, HF readmission, cardiovascular death, readmission of cerebral hemorrhage/stroke or gastrointestinal bleeding, and all-cause death) were recorded and analyzed. A total of 1,111 patients were enrolled for the present analysis. Based on whether the revascularization was complete or not, the patients were divided into the complete revascularization group (n=780) and the incomplete/no revascularization group (n=331). All patients were followed up with a median of 355days. The overall rates of unplanned repeated revascularization, HF readmission, and cardiovascular death were 6.6%, 5.0%, and 0.4%, respectively. Compared with incompletely/not revascularized patients, completely revascularized patients had a lower rate of unplanned repeated revascularization (10.9% vs 4.7%, p <0.001) and cardiovascular death (0.9% vs 0.1%, p=0.048). However, HF readmission, readmission of cerebral hemorrhage/stroke or gastrointestinal bleeding, and noncardiac death were comparable between the 2 groups. The regression analysis showed that hyperlipidemia, previous myocardial infarction, in-stent restenosis, and way of revascularization were associated with the composite events of unplanned repeated revascularization, HF readmission, and cardiovascular death during the follow-up. Complete revascularization may reduce unplanned repeated revascularization and cardiovascular death for patients with HFpEF and CAD.

Diagnosis of heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) currently causes about half of the heart failure related hospitalizations. With the aging of the population and increasing prevalence of risk factors and comorbidities, such as arterial hypertension, diabetes mellitus and obesity, HFpEF prevalence is expected to increase as well. With regards to quality of life, overall morbidity, and mortality, HFpEF patients have a similarly adverse prognosis as patients with heart failure with reduced ejection fraction. The leading symptoms of exertional dyspnea and exercise intolerance with concomitant clinical signs of heart failure should, therefore, prompt diagnostic tests to exclude or confirm HFpEF. Considering the main pathophysiological mechanisms, echocardiography is crucial to non-invasively identify signs of left ventricular (LV) hypertrophy, impaired myocardial relaxation, and elevated filling pressures. Elevated NT-proBNP may furthermore indicate increased LV wall stress and volume overload. If the results of these investigations are inconclusive, parameters of elevated filling pressures can be measured invasively by right or left heart catheterization. High pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) may confirm a HFpEF diagnosis. Ongoing studies are investigating potential distinct phenotypes within the HFpEF patient group.

Variability in approach to exercise stress echocardiography for diagnosis of heart failure with preserved ejection fraction: an international survey on real-world practice

Abstract Aims The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging based on resting assessments. Exercise echocardiography is often used to unmask abnormalities that develop during exercise, but the diagnostic criteria have not been standardized. This study aimed to elucidate how cardiologists utilize exercise echocardiography to diagnose HFpEF in real-world practice. Methods and results An international web-based survey involving 87 cardiologists was performed. We also performed a retrospective cross-sectional study to investigate the impact of different exercise echocardiographic diagnostic criteria in 652 dyspnoeic patients who underwent exercise echocardiography. The HFA-PEFF algorithm was the most commonly used exercise echocardiography criterion for HFpEF diagnoses (48%), followed by the ASE/EACVI criteria (24%) and other combinations of multiple parameters (22%). Among 652 patients, the proportion of HFpEF diagnosis varied substantially according to the criteria used ranging from 20.1% (ASE/EACVI criteria) to 44.3% (HFA-PEFF algorithm). Many cases (49.4–70.5%) remained indeterminate after exercise echocardiography, but only 41% of surveyed cardiologists would utilize exercise right heart catheterization to resolve an indeterminate result. Despite these diagnostic uncertainties, 54% of surveyed cardiologists would utilize exercise echocardiography results to initiate sodium–glucose co-transporter 2 inhibitors. Conclusion In real-world practice, exercise echocardiographic criteria utilized across cardiologists vary, which meaningfully impacts the frequency of HFpEF diagnoses, with indeterminate results being common. Despite these diagnostic uncertainties, many cardiologists initiate pharmacotherapy based on exercise echocardiography. The lack of consensus on universal diagnostic criteria for exercise echocardiography and approaches to indeterminate results may limit the delivery of evidence-based treatment for HFpEF.

Artificial intelligence methods for improved detection of undiagnosed heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) remains under-diagnosed in clinical practice despite accounting for nearly half of all heart failure (HF) cases. Accurate and timely diagnosis of HFpEF is crucial for proper patient management and treatment. In this study, we explored the potential of natural language processing (NLP) to improve the detection and diagnosis of HFpEF according to the European Society of Cardiology (ESC) diagnostic criteria. In a retrospective cohort study, we used an NLP pipeline applied to the electronic health record (EHR) to identify patients with a clinical diagnosis of HF between 2010 and 2022. We collected demographic, clinical, echocardiographic and outcome data from the EHR. Patients were categorized according to the left ventricular ejection fraction (LVEF). Those with LVEF ≥50% were further categorized based on whether they had a clinician-assigned diagnosis of HFpEF and if not, whether they met the ESC diagnostic criteria. Results were validated in a second, independent centre. We identified 8606 patients with HF. Of 3727 consecutive patients with HF and LVEF ≥50% on echocardiogram, only 8.3% had a clinician-assigned diagnosis of HFpEF, while 75.4% met ESC criteria but did not have a formal diagnosis of HFpEF. Patients with confirmed HFpEF were hospitalized more frequently; however the ESC criteria group had a higher 5-year mortality, despite being less comorbid and experiencing fewer acute cardiovascular events. This study demonstrates that patients with undiagnosed HFpEF are an at-risk group with high mortality. It is possible to use NLP methods to identify likely HFpEF patients from EHR data who would likely then benefit from expert clinical review and complement the use of diagnostic algorithms.

Diagnostic and prognostic value of the HFA-PEFF score for heart failure with preserved ejection fraction: a systematic review and meta-analysis.

To assess the diagnostic and prognostic performances of the Heart Failure Association Pre-test Assessment, Echocardiography & Natriuretic Peptide, Functional Testing, Final Etiology (HFA-PEFF) score for heart failure with preserved ejection fraction (HFpEF) in a comprehensive manner. PubMed, Embase, Cochrane Library, and Web of Science were comprehensively searched from the inception to June 12, 2023. Studies using the "Rule-out" or "Rule-in" approach for diagnosis analysis or studies on cardiovascular events and all-cause death for prognosis analysis were included. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was adopted to assess the quality of diagnostic accuracy studies. The sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic (SROC) curve (AUC) were presented with 95% confidence intervals (CIs). For CVEs and all-cause death, the hazard ratio (HR) values were calculated. Fifteen studies involving 6420 subjects were included, with 9 for diagnosis analysis, and 7 for prognosis analysis. For the diagnostic performance of the HFA-PEFF score, with the "Rule-out" approach, the pooled SEN was 0.96 (95%CI: 0.94, 0.97), the pooled SPE was 0.39 (95%CI: 0.37, 0.42), and the pooled AUC was 0.85 (95%CI: 0.67, 1.00), and with the "Rule-in" approach, the pooled SEN was 0.59 (95%CI: 0.56, 0.61), the pooled SPE was 0.86 (95%CI: 0.84, 0.88), and the pooled AUC was 0.83 (95%CI: 0.79, 0.87). For the predictive performance of the HFA-PEFF score, regarding CVEs, the pooled SEN was 0.63 (95%CI: 0.58, 0.67), the pooled SPE was 0.53 (95%CI: 0.49, 0.58), and the pooled AUC was 0.65 (95%CI: 0.40, 0.90), and concerning All-cause death, the pooled SEN was 0.85 (95%CI: 0.81, 0.88), the pooled SPE was 0.48 (95%CI: 0.44, 0.52), and the pooled AUC was 0.65 (95%CI: 0.47, 0.83). A higher HFA-PEFF score was associated with a higher risk of all-cause death (HR 1.390, 95%CI 1.240, 1.558, P < 0.001). The HFA-PEFF score might be applied in HFpEF diagnosis and all-cause death prediction. More studies are required for finding validation.

Obesity-Related Differences in Pathomechanism and Outcomes in Patients With HFpEF: A CMR Study

BackgroundClinical significance of an integrated evaluation of epicardial adipose tissue (EAT) and the right ventricle (RV) in heart failure with preserved ejection fraction (HFpEF) is unknown. ObjectivesThe authors investigated the potential of EAT and RV quantification for obesity-related pathophysiology and risk stratification in obese HFpEF patients using cardiovascular magnetic resonance (CMR). MethodsA total of 150 patients (obese, body mass index ≥30 kg/m2; n = 73, nonobese, body mass index <30 kg/m2; n = 77) with a clinical diagnosis of HFpEF undergoing CMR were retrospectively identified. EAT volume surrounding both ventricles were quantified with manual delineation on cine images. Total RV volume (TRVV) was calculated as the sum of RV cavity and mass at end-diastole. The endpoint was the composite of all-cause mortality and first HF hospitalization. ResultsDuring a median follow-up of 46 months, 39 nonobese patients (51%) and 32 obese patients (44%) experienced the endpoint. EAT was a prognostic biomarker regardless of obesity and was independently correlated with TRVV. In obese HFpEF, EAT correlated with RV longitudinal strain (r = 0.32, P = 0.006), and increased amount of EAT and TRVV was associated with greater left ventricular end-diastolic eccentric index (r = 0.36, P = 0.002). The integration of RV quantification into EAT provided improved risk stratification with a C-statistic increase from 0.70 to 0.79 in obese HFpEF. Obese patients with EAT<130 ml and TRVV<180 ml had low risk (annual event rate 3.2%), while those with increased EAT ≥130 ml and TRVV ≥180 ml had significantly higher risk (annual event rate 11.8%; P < 0.001). ConclusionsCMR quantification of EAT and RV structure provides additive risk stratification for adverse outcomes in obese HFpEF.

Effectiveness of a cardiac rehabilitation program on biomechanical, imaging, and physiological biomarkers in elderly patients with heart failure with preserved ejection fraction (HFpEF): FUNNEL + study protocol

BackgroundPatients with heart failure with preserved ejection fraction (HFpEF) have a low functional status, which in turn is a risk factor for hospital admission and an important predictor of survival in HFpEF. HFpFE is a heterogeneous syndrome and recent studies have suggested an important role for careful, pathophysiological-based phenotyping to improve patient characterization. Cardiac rehabilitation has proven to be a useful tool in the framework of secondary prevention in patients with HFpEF. Facilitating decision-making and implementing cardiac rehabilitation programs is a challenge in public health systems for HFpEF management. The FUNNEL + study proposes to evaluate the efficacy of an exercise and education-based cardiac rehabilitation program on biomechanical, physiological, and imaging biomarkers in patients with HFpEF.MethodsA randomised crossover clinical trial is presented among people older than 70 years with a diagnosis of HFpEF. The experimental group will receive a cardiac rehabilitation intervention for 12 weeks. Participants in the control group will receive one educational session per week for 12 weeks on HFpEF complications, functional decline, and healthy lifestyle habits. VO2peak is the primary outcome. Biomechanical, imaging and physiological biomarkers will be assessed as secondary outcomes. Outcomes will be assessed at baseline, 12 weeks, and 24 weeks.DiscussionIdentifying objective functional parameters indicative of HFpEF and the subsequent development of functional level stratification based on functional impairment ("biomechanical phenotypes") may help clinicians identify cardiac rehabilitation responders and non-responders and make future clinical decisions. In this way, future pharmacological and non-pharmacological interventions, such as exercise, could be improved and tailored to improve quality of life and prognosis and reducing patients' hospital readmissions, thereby reducing healthcare costs.Trial registrationNCT05393362 (Clinicaltrials.gov).

Left bundle branch area pacing improves right ventricular function in heart failure with preserved ejection fraction: evidence from PROPHET trial

Abstract Background Left bundle branch area pacing (LBBAP) has emerged as a promising pacing strategy, especially for patients with heart failure. However, the impact of LBBAP on hemodynamics and cardiac function in heart failure with preserved ejection fraction (HFpEF) has not been investigated yet. Aim To investigate the hemodynamic response and change of cardiac function of LBBAP in patients with HFpEF. Methods This prospective cohort study enrolled patients with preserved left ventricular ejection fraction who were receiving LBBAP, and two cohorts (non-HFpEF cohort and HFpEF cohort) were built based on diagnosis of HFpEF. Hemodynamics before and after LBBAP were measured using right heart catheterization (RHC). And the changes of cardiac function were evaluated by transthoracic speckle tracking echocardiography (STE). Results 30 consecutive patients were included in the study, with 17 patients in the non-HFpEF group and 13 patients in the HFpEF group. Preprocedural STE showed worsened right ventricular function in the HFpEF group indicated by global longitudinal strain rate, free-wall strain rate, fractional area change, Tricuspid annular pulmonary systolic excursion and Tei index. And RHC showed elevated right ventricular stroke work index (RVSWI, 8.6±4.1 non-HFpEF vs 15.0±5.6 HFpEF, P = 0.170). While post-LBBAP evaluation showed a more significant reduction in RVSWI in the HFpEF group (6.7±2.5 (reduction 22.1%) non-HFpEF vs 8.0±1.0 (reduction 46.7%) HFpEF, P = 0.043). Besides, post-LBBAP STE showed improvement of right ventricular function, despite no significant difference in the extent of improvement was found between groups. Conclusion LBBAP might be more beneficial to patients with HFpEF as it could improve right ventricular function by alleviating the workload of right ventricle. Long-term benefit of LBBAP in HFpEF requires further investigation.

Inter-atrial block and atrial fibrillation predict cardiac adverse events in heart failure with preserved ejection fraction

Abstract Background Atrial fibrillation (AF) is a prognostic risk-factor in heart failure with preserved ejection fraction (HFpEF). Earlier stages of atrial dysfunction identified by the ECG, particularly inter-atrial block (IAB), may provide additional risk predictions in HFpEF patients in sinus rhythm. Purpose To assess the prevalence of IAB in patients diagnosed with HFpEF compared to non-HFpEF, and to evaluate the prognostic association of IAB and AF in patients diagnosed with HFpEF. Methods Consecutive symptomatic patients referred for a systematic diagnostic work-up to rule-in or rule-out HFpEF were included. The diagnosis of HFpEF was based on current guidelines (including HFA-PEFF and H2FPEF algorithms) and confirmed by consensus of multiple experienced HF specialists. Patients in whom HFpEF was ruled-out were included as non-HFpEF. We excluded patients with cardiac valve interventions before or up to 1 year after baseline, or with paced rhythm during IAB assessment. ECGs at baseline were assessed in detail for P-wave duration, morphology, and presence of IAB using digital calipers by investigators blinded to clinical data. IAB was defined based on a P-wave duration of &amp;gt;120ms. Patients with HFpEF and non-HFpEF were grouped into either i) AF based on ECG or medical history, ii) IAB based on ECG, or iii) no IAB or AF based on ECG. Adverse events were evaluated only in HFpEF patients and included HF hospitalization, cardiac or sudden death, and a composite of both. Results 372 patients with HFpEF and 68 non-HFpEF were included (females: 67.7% vs. 64.7%, p = 0.726; mean age: 75±7 vs. 67±10 years, p&amp;lt;0.001). AF was more common in HFpEF than non-HFpEF (64.8% vs. 23.5%, p&amp;lt;0.001). In sinus rhythm, presence of IAB was comparable between HFpEF and non-HFpEF (87.0% vs. 80.8%). During a mean follow-up of 3.2±1.6 years in HFpEF patients, more adverse cardiac events were observed when AF was present (23.7%, HR 10.6 [95%CI 1.5-1334.4]) compared to IAB (10.5%, HR 4.2 [95%CI 0.56-542.6]) and no IAB (0%), p = 0.0004 (Figure 1). Pairwise comparisons confirmed these observations: AF vs. IAB p = 0.006, AF vs. no IAB p = 0.031. In HFpEF patients with sinus rhythm, a trend was found for more adverse events when IAB was present versus no IAB (p = 0.06). Conclusion Patients with HFpEF have a higher prevalence of AF and similar prevalence of IAB compared to symptomatic patients ruled-out for HFpEF. Presence of IAB or AF in HFpEF may predispose to adverse cardiac events in patients without severe valve disease. IAB may enrich cardiac risk stratification in addition to AF in HFpEF.Survival curves for no IAB, IAB, and AF

Prevalence and incidence of diastolic dysfunction in new-onset atrial fibrillation: implications for clinical and preclinical HFpEF

Abstract Background Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are closely associated diseases that frequently coexist. However, due to the overlapping symptoms, the diagnosis of HFpEF can be overlooked with symptoms being attributed to AF. Purpose We aimed to investigate the prevalence of diastolic dysfunction (DD) in patients with new-onset AF compared to sinus rhythm (SR), study changes in diastolic function parameters over time in the two groups and compare the incidence of DD at follow-up. Methods Adults with new diagnosis of AF and adults in SR were identified. Patients with previous cardiac surgeries, congenital heart disease, hypertrophic or infiltrative cardiomyopathy, primary mitral disease, left-sided valve disease, low ejection fraction, enlarged left ventricle, or with no 6-month follow-up echocardiogram were excluded. Diastolic function was assessed through 4 components: mitral medial e’ &amp;lt;0.07 m/sec, mitral medial E/e’ &amp;gt;15 in SR and &amp;gt;11 in AF, TR velocity &amp;gt;2.80 m/sec, and left atrial volume index &amp;gt;34 ml/m2, with severe DD (SDD) defined by ≥3/4 findings and moderate DD (MDD) by ≥2/4 abnormal diastolic function parameters. Annualized changes were calculated as the difference between follow-up and baseline values divided by years in between. In a secondary analysis, patients with new-onset AF were propensity score-matched to patients with SR in a 3:1 ratio based on age, sex, body mass index, and comorbidities. Results Overall, 1,747 patients with incident AF (median age 67 years; 34% females) and 29,623 in SR (median age 59 years; 51% females) were included. New-onset AF was independently associated with the presence of SDD vs SR (8% vs 2%) and MDD (25% vs 11%, p&amp;lt;.001 for both in adjusted analysis). Over median follow-up of 3.2 (IQR 1.6-5.8) years, annualized severity progression in each of the 4 diastolic function parameters was greater in the AF group (p&amp;lt;.001 for all), Table. The incidence rates of SDD and MDD were 3.7 and 8.8 per 100-person year, respectively, in AF versus 1.1 and 3.6 per 100-person years, respectively, in SR (p&amp;lt;.001 for both at univariate and multivariable analysis), Figure. Results were similar in the propensity-score matched analysis. Conclusions Patients with new-onset AF more commonly have moderate or severe diastolic dysfunction that indicates the presence of potentially overlooked clinical HFpEF (when symptoms exist) or preclinical HFpEF (when symptoms are absent) compared to patients in SR. In long-term follow-up, patients with AF display accelerated progression in DD; suggesting that therapies to prevent progression to symptomatic HFpEF may be highest value in this patient population.

Impact of different types of heart failure on coronavirus disease 2019 infection outcomes

Abstract Background Pre-existing cardiovascular disease has been associated with increased mortality in patients with coronavirus disease 2019 (COVID-19). However, the impact of different types of heart failure in unvaccinated patients with COVID-19 infection has been understudied. Purpose In this study, we compare the in-hospital outcomes of patients with COVID-19 and chronic heart failure with reduced ejection fraction (HFrEF) against patients with COVID-19 and chronic heart failure with preserved ejection fraction (HFpEF). Methods This was a retrospective cohort study done by utilizing the 2020 National Inpatient Sample database. We identified patients admitted to the hospital with a principal diagnosis of COVID-19 infection and a secondary diagnosis of either chronic HFrEF or HFpEF. We conducted propensity score matching using a greedy nearest neighbor 1:1 model. Multivariable logistic regression, adjusted for age, sex, hospital characteristics (bed size, location, region), health insurance and comorbidities was used to compare mortality. The comorbidities adjusted for included atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease, coronary artery disease, hypertension, obesity, prior myocardial infarction and type 2 diabetes mellitus. The categorical and continuous variables were analyzed by Pearson’s chi-squared and Student t-test respectively. Results 12,518 patients met our inclusion criteria. Patients with COVID-19 infection and chronic HFrEF had 1.11 times higher odds of suffering in-hospital mortality compared to patients with COVID-19 infection and chronic HFpEF (aOR 1.11, 95% CI: 1.01-1.21; p = 0.03). When separated by race, there was no difference in mortality between our two cohorts (Figure 1). Patients with COVID-19 infection and chronic HFrEF were more likely to have acute hepatic failure (1.2% vs 0.6%, p &amp;lt; 0.001), ventricular tachycardia (6.7% vs 3.1%, p &amp;lt; 0.001) and ventricular fibrillation (0.6% vs 0.2%, p &amp;lt; 0.001), but less likely to have acute respiratory distress syndrome (5.0% vs 6.6%, p &amp;lt; 0.001, Table 1). In terms of comorbidities, patients with both COVID-19 and chronic HFrEF were more likely to have atrial fibrillation (22.8% vs 21.3%, p = 0.03) coronary artery disease (39.5% vs 35.1%, p &amp;lt; 0.001) and prior myocardial infarction (8.8% vs 6.4%, p &amp;lt; 0.001, Table 1). These patients also had shorter hospital stays (8.4 days vs 9.0 days, p &amp;lt; 0.001), but there was no difference in mean total hospital charges ($87,975.84 vs $88,715.96, p = 0.75, Table 1). Conclusion Patients with COVID-19 and chronic HFrEF had higher odds of suffering in-hospital mortality compared to patients with COVID-19 and chronic HFpEF. These patients were also more likely to have acute hepatic failure, ventricular tachycardia and ventricular fibrillation. Further studies should investigate how COVID-19 vaccination status influences the outcomes of this vulnerable population.

Exercise gas exchange and echo-derived analysis in HFpEF based on patterns of oxygen peripheral utilization

Abstract Background Exercise limitation is a key signature of heart failure with preserved ejection fraction (HFpEF) syndrome evolution with studies highlighting a significant cardiac reserve limitation and others identifying a predominant limit in the peripheral VO2 kinetics and utilization. Aims To clarify the cardiopulmonary and hemodynamic response in HFpEF according to the high or low peripheral O2 utilization patterns during maximal exercise. Materials and Method 38 patients with a HFpEF diagnosis based on the ESC HFpEFF criteria underwent cardiopulmonary exercise test (CPET) combined with stress echocardiography. Patients were divided in two groups according to the median peak c(A-V) O2 difference (Group 1: &amp;lt; 11 mL/dL and Group 2: &amp;gt; 11 mL/dL). Cardiac output (CO) was calculated by echocardiography according to the formula LVOT velocity integral x LVOT area. Data were obtained after a familiarization CPET session. Results Group 1 and 2 presented similar rest demographic, left and right hemodynamic data (table). The relationship between CO and c (A-V) O2 in terms of VO2 isopleths at peak exercise were not related to any difference in CO (figure) Conclusions In HFpEF, an impairment in O2 utilization during exercise appears independent of the cardiac reserve response (similar peak CO increase) but rather peripheral mechanisms implicated in O2 diffusion/release seem to play a dominant role, emerging as selective therapeutic targets for improving functional capacity and symptoms.

Abstract 14945: Left Bundle Branch Area Pacing Improves Right Ventricular Function in Heart Failure With Preserved Ejection Fraction: Evidence From PROPHET Trial

Introduction: Left bundle branch area pacing (LBBAP) has emerged as a promising pacing strategy, especially for patients with heart failure. However, the impact of LBBAP on hemodynamics and cardiac function in heart failure with preserved ejection fraction (HFpEF) has not been investigated yet. Hypothesis: LBBAP could improve cardiac function of patients with HFpEF. Methods: This prospective cohort study enrolled patients with preserved left ventricular ejection fraction who were receiving LBBAP, and two cohorts (non-HFpEF cohort and HFpEF cohort) were built based on diagnosis of HFpEF. Hemodynamics before and after LBBAP were measured using right heart catheterization (RHC). And the changes of cardiac function were evaluated by transthoracic speckle tracking echocardiography (STE) Results: 30 consecutive patients were included in the study, with 17 patients in the non-HFpEF group and 13 patients in the HFpEF group. Preprocedural STE showed worsened right ventricular function in the HFpEF group indicated by global longitudinal strain rate, free-wall strain rate, fractional area change, Tricuspid annular plane systolic excursion and Tei index. And RHC showed elevated right ventricular stroke work index (RVSWI, 8.6±4.1 non-HFpEF vs 15.0±5.6 HFpEF, P=0.170). While post-LBBAP evaluation showed a more significant reduction in RVSWI in the HFpEF group (6.7±2.5 (reduction 22.1%) non-HFpEF vs 8.0±1.0 (reduction 46.7%) HFpEF, P=0.043). Besides, post-LBBAP STE showed improvement of right ventricular function, despite no significant difference in the extent of improvement was found between groups. Conclusions: LBBAP might be more beneficial to patients with HFpEF as it could improve right ventricular function by alleviating the workload of right ventricle. Long-term benefit of LBBAP in HFpEF requires further investigation.

Abstract 18410: Correlation Between Body Mass Index and NT-proBNP Levels in Heart Failure With Preserved Ejection Fraction: Implications for Clinical Outcomes

Introduction: N-terminal pro B type natriuretic peptide (NT-proBNP) is associated with increased cardiovascular events in heart failure with preserved ejection fraction (HFpEF). Adiposity is inversely correlated with NT-proBNP. It remains unclear whether obese HFpEF patients exhibit disproportionate outcomes with lower NT-proBNP. Hypothesis: We aimed to study the relationship between NT-proBNP and BMI in the Johns Hopkins University (JHU) HFpEF cohort to identify patient characteristics with increased NT-proBNP in obese HFpEF patients, adjusting for the inverse relation between NT-proBNP and BMI. Methods: We identified 338 individuals from June 2013 to November 2022. Univariate linear regression was performed between NT-proBNP and BMI. The cohort was split based on the median BMI and studentized residuals from NT-proBNP-BMI relationship (low BMI high BNP [Group 1] high BMI high BNP [Group 2] low BMI low BNP [Group 3] high BMI low BNP [Group 4]). Kruskal-Wallis test or Chi-square test was used to compare groups. Results: The median BMI of the cohort was 37kg/m 2 , and with every 1kg/m 2 increase in the BMI, the cut-off for elevated NT-proBNP reduced by 4 pg/ml. High BMI HFpEF patients were younger, predominantly female, and on diuretics (p&lt;0.05 for all), independent of their NT-proBNP levels. Group 4 patients performed better on the 6-minute walk test (240±136 m), had better renal function (eGFR: 68.7±27.3), and less left ventricular (LV) hypertrophy and only mild diastolic dysfunction on echocardiography. Surprisingly, Group 2 resembled Group 1 despite having 70% reduced median NT-proBNP (1898[1047,4409] vs 574[207,1322], p&lt;0.0001). Both “high BNP” groups exhibited lower event free survival for all -cause mortality(p=0.0001) and HF-hospitalization(p&lt;0.05). Conclusions: NT-proBNP is predictive of clinical outcomes in HFpEF even in the presence of obesity. BMI adjusted NT-proBNP may be useful in the diagnosis and prognosis of HFpEF.

Abstract 16841: Skeletal Muscle Fat Predicts Exercise Intolerance and Decreased Survival in Symptomatic Heart Failure With Preserved Ejection Fraction

Introduction: Heart failure with preserved ejection fraction (HFpEF) is characterized by marked exercise intolerance (EI) and increased mortality. HFpEF is now thought to involve multi-organ dysfunction and skeletal muscle (SkM) changes including muscle loss and muscle fatty infiltration have been reported in HFpEF patients. However, it is not known if SkM changes are associated with cardiovascular (CV) mortality. Hypothesis: Skeletal muscle fat accumulation in symptomatic HFpEF patients is associated with worse EI and decreased survival. Methods: Patients with a clinical diagnosis of HFpEF and left ventricular ejection fraction &gt; 50% (n=64, age 65.2±11.2, BMI 38.6±8.2, mean±SD, 53% women) underwent 3T conventional magnetic resonance imaging (MRI) of the calf muscle to determine SkM mass and T2-weighted MRI for SkM fat fraction (FF) with subcutaneous fat excluded. Baseline EI was quantified by six-minute walk distance (6MW). HFpEF patients were followed prospectively for a minimum of 18 months for survival (median follow up 39.3 months). Simple linear regression was used to determine relationships with EI while Kaplan-Meier survival curves with log rank tests were created to explore CV mortality. Results: SkM FF was closely and inversely associated with 6MW (1A), but SkM mass (1B) was not, indicating that EI in HFpEF is more closely associated with SkM quality than quantity. SkM FF was not related to body mass index (BMI) (1C). When the HFpEF cohort was stratified based on median FF (median=18.79%), SkM FF predicted significantly worse survival from CV death (1D, p=0.0192). Conclusions: This is the first report to show that SkM fat content predicts cardiovascular mortality in HFpEF patients. Further, EI in HFpEF patients is closely associated with SkM fat accumulation but not sarcopenia. Thus, reducing SkM fat content may represent a new target for reducing EI and improving CV survival in HFpEF patients.

Abstract 16269: Heart Failure With Preserved Ejection Fraction and Sudden Cardiac Death in the General Population

Background: Published data indicate that 50% of individuals with heart failure and reduced ejection fraction (HFrEF) suffer sudden cardiac death (SCD), however the burden of SCD in heart failure with preserved ejection fraction (HFpEF) remains inconclusive. Aim: Determine the prevalence of HFpEF in a community-based cohort of SCD. Methods: We prospectively identified cases with out-of-hospital SCD in a large metro area of the US Northwest (Pop. 1 million, 2002-2017) and determined HF status prior to SCD based on review of clinical records. Heart failure was subdivided into HFpEF (EF≥50%), HFmrEF (EF 40%-50%), and HFrEF (EF≤40%). In addition, since HFpEF is often underdiagnosed, we evaluated a modified H2FPEF algorithm for the identification of HFpEF among our SCD cohort with unknown HF subtypes. The score was comprised of clinical variables including age, BMI, atrial fibrillation, hypertension, and myocardial infarction. Score accuracy was assessed using receiver operating characteristic (ROC) analysis comparing known HFpEF from clinical records and echocardiography versus non-HF subjects. Next, the score was used to identify missing HFpEF cases within the HF and SCD population. Results: Among 4,683 total SCD cases, 1,013 (22%) had a clinical history of HF. Prevalence of HF sub-types was 42% for HFpEF, 19% for HFmEF and 39% for HFrEF cases. An algorithm score of 5 or greater differentiated HFpEF subjects from non-HF subjects with an AUC of 0.68 (p &lt; 0.01). The algorithm was then deployed on cases with an unknown heart failure subtype and an additional 117 HFpEF subjects were identified. The adjusted total prevalence of HFpEF was 542 subjects (53%) in the SCD the cohort with HF. Conclusion: At least 40% of the SCD cases with HF carry a diagnosis of HFpEF, and our estimates suggest the prevalence may be as high as 53%. Ultimately, these findings highlight the need to develop effective options for primary prevention of SCD in HFpEF patients.

Heart Failure With Preserved Ejection Fraction and the Diagnosis of Pulmonary Hypertension

Heart failure with preserved ejection fraction (HFpEF) is now the most common cause of pulmonary hypertension (PH), and the diagnosis of HFpEF should be considered in any patient with a preserved left ventricular systolic function being evaluated for PH. Accurately diagnosing HFpEF as compared with pulmonary arterial hypertension has critical treatment implications, given the vastly different treatment options available, and can be accurately guided using exercise right heart catheterization. In this review, the diagnostic approach and treatment implications of PH in patients at risk for HFpEF will be discussed.

The prevalence of coronary microvascular dysfunction (CMD) in heart failure with preserved ejection fraction (HFpEF): a systematic review and meta-analysis.

To date, studies on the prevalence of coronary microvascular dysfunction (CMD) in heart failure with preserved ejection fraction (HFpEF) have not been summarized and analyzed as a whole. We conducted this systematic review and meta-analysis to assess the prevalence of CMD in patients with HFpEF. The PubMed, Cochrane, and Embase databases were searched from dates of inception until May 1, 2023. The primary outcome was the prevalence of CMD in patients with HFpEF, and values of CMD prevalence were pooled using a random-effects model. In total, 10 studies involving 1267 patients, including 822 with HFpEF and 445 without HFpEF, were included. The pooled prevalence of CMD in patients with HFpEF was 71% (95% CI, 0.63-0.79). In the subgroup analysis, the prevalence of CMD was 79% (95% CI, 0.71-0.87) by invasive measurement and 66% (95% CI, 0.54-0.77) by noninvasive measurement and 67% (95% CI, 0.52-0.82) with CFR < 2.0 and 75.0% (95% CI, 0.71-0.79) with CFR < 2.5. The prevalence of endothelium-independent CMD and endothelium-dependent CMD was 62% (95% CI, 0.53-0.72) and 50% (95% CI, 0.19-0.81), respectively. The prevalence of CMD was 74% (95% CI = 0.69-0.79) and 66% (95% CI = 0.41-0.90) in prospective and retrospective studies, respectively. Compared with the control group, patients with HFpEF had a significantly lower CFR (MD = - 1.28, 95% CI = - 1.82 to - 0.74, P < 0.01) and a higher prevalence of CMD (RR = 2.21, 95% CI = 1.52 to 3.20, P < 0.01). Qualitative analysis demonstrated that CMD might be associated with poor clinical outcomes in patients with HFpEF. In conclusion, this is the first systematic review and meta-analysis of all studies reporting the prevalence of CMD in patients with HFpEF. Our study demonstrates that CMD is common in patients with HFpEF and might be associated with poor clinical outcomes in these patients. Clinicians should attach importance to CMD in the diagnosis and treatment of HFpEF. The number of studies in this field is relatively small. Therefore, more high-quality studies are needed to explore the diagnostic and prognostic value of CMD and the potential role of CMD as a therapeutic target in patients with HFpEF.