Heart Failure With Preserved Ejection Fraction Patients Research Articles

Efficacy and limitation of nonparoxysmal atrial fibrillation ablation in patients with heart failure with preserved ejection fraction.

Catheter ablation for atrial fibrillation (AF) reduces heart failure (HF) hospitalization in patients with HF with preserved ejection fraction (HFpEF). However, the long-term outcomes and subclinical HF after nonparoxysmal AF ablation in HFpEF patients have not been fully evaluated. One-hundred-ninety nonparoxysmal AF patients with left ventricular ejection fraction ≥50% who underwent first-time AF ablation were studied. HFpEF was diagnosed from a history of congestive HF and/or combined criteria of N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and transthoracic echocardiogram parameters, including average septal-lateral E/e' and tricuspid regurgitation peak velocity. Ninety-five patients with HFpEF (HFpEF group) were compared with 95 patients without HF (CNT group). Low voltage area (LVA) was defined as an area with a bipolar electrogram of <0.5 mV covering >5% of the total left atrial surface. The primary endpoint was a composite of death from any cause or hospitalization for worsening HF. The secondary endpoint was subclinical HFpEF defined from NT-proBNP concentration and average septal-lateral E/e' or tricuspid regurgitation peak velocity at 6-12 months after the procedure irrespective of the rhythm. Kaplan-Meier curves showed that the primary composite endpoint did not differ between the two groups (mean follow-up period 707 ± 75 days, log-rank p = 0.5330). However, significantly more patients in the HFpEF group reached the secondary endpoint (42 [44%] vs. 13 [14%], p < 0.0001). Multivariate analysis revealed that a high preablation NT-proBNP (odds ratio [OR] 1.001, 95% confidence interval [CI] 1.001-1.002, p = 0.0040) and the existence of LVA (OR 5.983, 95% CI 1.463-31.768, p = 0.0194) independently predicted the secondary endpoint in HFpEF patients. After nonparoxysmal AF ablation, mortality of HFpEF patients was not inferior compared to patients without coexisting HF. However, subclinical HF occasionally persisted especially in HFpEF patients with a high preprocedure NT-proBNP concentration and LVA.

Association between trajectory of systolic blood pressure and outcomes in heart failure patients with preserved ejection fraction (HFpEF)

BackgroundThe optimal systolic blood pressure (SBP) in heart failure patients with preserved ejection fraction (HFpEF) remains controversial. We aim to assess the SBP trajectory and prognosis in HFpEF. Methods and ResultsPatients from Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) were classified into three SBP trajectory groups according to the follow-up blood pressure using a latent category trajectory model. The primary outcome was composite of cardiovascular death, cardiac arrest, and hospital readmission for heart failure. A total of 3388 patients (mean age 68.6 years, 48.5 % men) were included. Mean SBP maintained 128 mmHg in the stable SBP trajectory group, declined from 129 to 125 mmHg in the decreasing SBP trajectory group and rose from 132 to 143 mmHg in the increasing SBP trajectory group within 6 years. During a mean follow-up of 3.4 years, 654 individuals had a primary outcome. Incidence for both primary and secondary outcomes were higher in increasing SBP trajectory group and decreasing SBP trajectory group compared with stable SBP trajectory group. After adjustments, the decreasing SBP trajectory group was associated with increased risk of all outcomes (hazard ratio ≥1.32), the increasing SBP trajectory group was associated with all-cause hospitalization and stroke (hazard ratio ≥ 1.28). ConclusionThe decreasing or increasing SBP trajectory is associated with a high risk of cardiovascular events in HFpEF, suggesting a stable SBP trajectory group (≈130 mmHg) have lower incidence of cardiovascular events and mortality. Trials are necessary to determine the optimal SBP in HFpEF.

BNP and NT-proBNP as prognostic biomarkers for the prediction of adverse outcomes in HFpEF patients: A systematic review and meta-analysis.

Heart failure with preserved ejection fraction (HFpEF) presents a challenge in clinical practice due to its complexity and impact on morbidity and mortality. The aim of this systematic review and meta-analysis (SR/MA) was to evaluate the value of B-Type Natriuretic Peptide (BNP) and NT-proBNP in predicting overall adverse outcomes, cardiovascular events, and mortality, in patients with HFpEF. This SR/MA included observational studies and randomized controlled trials (RCTs) that reported the use of BNP and NT-proBNP as prognostic biomarkers for adverse outcomes in HFpEF patients. A comprehensive literature search was conducted using PubMed, EMBASE, and Google, without language restrictions, from inception until June 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The quality and risk of bias of the included studies were assessed using the Newcastle-Ottawa Scale (NOS). Twenty-two studies involving 10,158 HFpEF patients were included. The analysis showed that BNP is a significant predictor of overall adverse events in HFpEF patients, with an overall HR of 1.34 (95% CI: 1.20-1.52). Similarly, BNP was a significant predictor of cardiovascular events and mortality in HFpEF patients with a HR of 1.36 (95% CI 1.12-1.64) and HR of 1.44 (95% CI: 1.04-1.84), respectively. When analyzing data for NT-proBNP predictive potential, 3 studies confirmed that NT-proBNP is a significant independent prognostic indicator for adverse events, with an overall HR of 1.80 (95% CI: 1.38-2.35). Comparable results were seen for mortality, with higher NT-proBNP levels associated with increased mortality risk and the MA showing a HR of 1.65 (95% CI: 1.55-1.76). This systematic review highlights the valuable prognostic role of BNP and NT-proBNP in predicting overall adverse outcome, cardiovascular events, and mortality in HFpEF patients. Our findings underscore the importance of further research to establish standardized thresholds and investigate BNP and NT-proBNP's potential in predicting morbidity and mortality.

Commonalities of platelet dysfunction in heart failure with preserved ejection fraction and underlying comorbidities.

Heart failure with preserved ejection fraction (HFpEF) is characterized by a lack of a specific targeted treatment and a complex, partially unexplored pathophysiology. Common comorbidities associated with HFpEF are hypertension, atrial fibrillation, obesity and diabetes. These comorbidities, combined with advanced age, play a crucial role in the initiation and development of the disease through the promotion of systemic inflammation and consequent changes in cardiac phenotype. In this context, we suggest platelets as important players due to their emerging role in vascular inflammation. This review provides an overview of the role of platelets in HFpEF and its associated comorbidities, including hypertension, atrial fibrillation, obesity and diabetes mellitus, as well as the impact of age and sex on platelet function. These major HFpEF-associated comorbidities present alterations in platelet behaviour and in features linked to platelet size, content and reactivity. The resulting dysfunctional platelets can contribute to further increase inflammation, oxidative stress and endothelial dysfunction, suggesting an active role of these cells in the initiation and progression of HFpEF. Recent evidence shows that reduced platelet count and elevated mean platelet volume are associated with worsening heart failure in HFpEF patients. However, the specific mechanisms by which platelets contribute to HFpEF development and progression are still largely unexplored, with only a few studies investigating platelet function in HFpEF. We discuss the limited yet significant body of research investigating platelet function in HFpEF, emphasizing the need for more comprehensive studies. Additionally, we explore the potential mechanisms through which platelets may influence HFpEF, such as their interactions with the vascular endothelium and the secretion of bioactive molecules like cytokines, chemokines and RNA molecules. These interactions and secretions may play a role in modulating vascular inflammation and contributing to the pathophysiological landscape of HFpEF. The review underscores the necessity for future research to elucidate the precise contributions of platelets to HFpEF, aiming to potentially identify novel therapeutic targets and improve patient outcomes. The evidence presented herein supports the hypothesis that platelets are not merely passive bystanders but active participants in the pathophysiology of HFpEF and its comorbidities.

Endoplasmic reticulum stress and expression of nitric oxide synthases in heart failure with preserved and with reduced ejection fraction - pilot study.

Unfolded Protein Response (UPR), endoplasmic reticulum (ER) stress, and inducible nitric oxide synthase (iNOS) overexpression have been found to influence heart failure with preserved ejection fraction (HFpEF) pathogenesis. Their importance in heart failure with reduced ejection fraction (HFrEF) is not entirely established; there is little data involving a detailed comparison between HFpEF and HFrEF from this perspective. This pilot study aimed to compare circulating levels of Glucose-regulated protein 78kDa (GRP78) (ER - stress marker) and all NOS isoforms between both HFpEF and HFrEF and to analyze the correlation between these markers and the clinical characteristics of the patients. Forty-two patients with HFpEF and thirty-eight with HFrEF were involved in this study. Clinical characteristics and echocardiographic data were obtained. Basic laboratory tests were performed and ELISA tests for iNOS, endothelial NOS (eNOS), neuronal NOS (nNOS), and GRP78. Patients with HFpEF had lower circulating levels of GRP78 and higher iNOS concentrations when compared to HFrEF patients (P = 0.023, P < 0.0001, accordingly). The subgroup of the HFpEF population with eGFR < 60 mL/min/1.73m2 had higher nNOS and eNOS levels than HFpEF patients with normal GFR (P = 0.049, P = 0.035, respectively). In the HFrEF subgroup, patients with coexistent diabetes mellitus had elevated concentrations of nNOS compared to the subpopulation without diabetes mellitus (P = 0.041). There was a positive correlation between eNOS and nNOS concentrations (ρ = 0.86, P < 0.0001). In HFpEF, there is a more intensified iNOS overexpression, while in HFrEF, ER stress is more prominent.

The role of coronary microcirculation in heart failure with preserved ejection fraction: An unceasing odyssey.

Heart failure with preserved ejection fraction (HFpEF) represents an entity with complex pathophysiologic pathways, among which coronary microvascular dysfunction (CMD) is believed to be an important orchestrator. Research in the field of CMD has highlighted impaired vasoreactivity, capillary rarefaction, and inflammation as potential mediators of its development. CMD can be diagnosed via several noninvasive methods including transthoracic echocardiography, cardiac magnetic resonance, and positron emission tomography. Moreover, invasive methods such as coronary flow reserve and index of microcirculatory resistance are commonly employed in the assessment of CMD. As far as the association between CMD and HFpEF is concerned, numerous studies have highlighted the coexistence of CMD in the majority of HFpEF patients. Additionally, patients affected by both conditions may be facing an adverse prognosis. Finally, there is limited evidence suggesting a beneficial effect of renin-angiotensin-aldosterone system blockers, ranolazine, and sodium-glucose cotransporter-2 inhibitors in CMD, with further evidence being awaited regarding the impact of other pharmacotherapies such as anti-inflammatory agents.

Evaluating the Prognostic Value of the Modified H2FPEF Score in Patients With Heart Failure With Preserved Ejection Fraction.

The H2FPEF score, a convenient tool developed for diagnosing heart failure with preserved ejection fraction (HFpEF), exhibited useful prognostic utility in HFpEF. However, the applicability and the prognostic value of the H2FPEF score in Chinese HFpEF patients have yet to be fully confirmed. The study aimed to evaluate the effect of modified H2FPEF score on the prognosis of Chinese HFpEF patients. In this retrospective study, we calculated the H2FPEF scores by body mass index (BMI) ≥ 25 kg/m2 and 30 kg/m2 respectively, for 497 consecutive HFpEF patients in China. Subjects were divided into low- (0 - 3 points), intermediate- (4 - 6 points), and high-score (7 - 9 points) groups. The primary and secondary endpoints were heart failure (HF)-related events and acute coronary syndrome (ACS), respectively. Cox proportional hazard models were applied to calculate hazard ratios (HRs). Receiver operating characteristic (ROC) curves and areas under the curve (AUC) were used to evaluate the prediction of the H2FPEF score for adverse outcomes. Over a mean follow-up of 40.46 ± 6.52 months, the primary and secondary endpoints occurred in 168 patients (33.8%) and 97 patients (19.5%), respectively. By the definition of obesity as BMI ≥ 25 kg/m2, a higher incidence of HF-related events and ACS was observed among those with a higher modified H2FPEF score. The modified H2FPEF significantly predicted HF-related events (AUC: 0.723; 95% confidence interval (CI): 0.676 - 0.770; P < 0.001) and ACS (AUC: 0.670; 95% CI: 0.608 - 0.731; P < 0.014) with higher power than the H2FPEF score calculated by BMI ≥ 30 kg/m2. The cutoff of the modified H2FPEF score was 6.5 for detecting HF-related events and ACS. The modified H2FPEF score, using BMI ≥ 25 kg/m2 to define obesity, could more effectively predict the occurrence of subsequent cardiovascular events in Chinese HFpEF patients. The modified H2FPEF score above 6.5 is a risk factor for adverse cardiovascular events in HFpEF patients.

Catheter Ablation Versus Antiarrhythmic Therapy for Atrial Fibrillation in Heart Failure with Preserved Ejection Fraction

BackgroundClinical outcomes among patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) treated with catheter ablation (CA) versus antiarrhythmic therapy (AAT) are not well-known. ObjectivesThis study compared morbidity and mortality among patients with AF and HFpEF treated with CA versus AAT. MethodsAF and HFpEF patients from January 2017-June 2023 were identified in TriNetX, a large global population-based database. Patients with prior diagnosis of HFrEF or crossover between AAT and CA were excluded. Baseline characteristics including age, sex, BMI, type of AF, comorbidities, and cardiovascular medications were compared. The two groups were 1:1 propensity matched for outcomes analysis. All-cause mortality, cerebrovascular accident (CVA)/transient ischemic attack (TIA), and acute HF were compared with Kaplan-Meier curves. ResultsPatients treated with CA (n=1959) and AAT (n=7689) were 1:1 propensity matched yielding 3632 patients with no significant differences in baseline characteristics. Compared to AAT, CA was associated with decreased mortality (9.2% vs. 20.5%; hazard ratio [HR]: 0.431; 95% confidence interval [CI]: 0.359 to 0.518; p<0.001). Additionally, CA was associated with reduced HFpEF (HR: 0.638; 95% CI, 0.550 to 0.741; p<0.001) and acute HFrEF (HR: 0.645; 95% CI, 0.452 to 0.920; p=0.015). There was no difference in composite of CVA/TIA (HR: 0.935; 95% CI: 0.725 to 1.207; p=0.607). ConclusionIn this retrospective study of patients with AF and HFpEF, CA was associated with lower mortality and risk of acute heart failure when compared with AAT.

Clinical Implications of Pretest Probability of HFpEF on Outcomes in PrecapillaryPulmonary Hypertension.

Patients with group 1 pulmonary hypertension (PH) and risk factors for heart failure with preserved ejection fraction (HFpEF) demonstrate worse response to pulmonary vasodilator therapy. The mechanisms and optimal diagnostic approach to identify such patients remain unclear. The purpose of this study was to compare exercise capacity, cardiac function, and hemodynamic responses to provocative maneuvers among patients with group 1 PH based upon pretest probability of HFpEF. Pretest probability for HFpEF was determined using the validated HFpEF-ABA algorithm based on age, body mass index, and history of atrial fibrillation among group 1 PH patients recruited to the multicenter PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) study. Functional capacity, quality of life, and dynamic pulmonary capillary wedge pressure (PCWP) responses were compared between those with low (<25%), intermediate (25%-74%), and high (≥75%) ABA score-based HFpEF probability. Among 424 patients with group 1 PH, 54% (n=228) had intermediate HFpEF probability and 15% (n=64) had high HFpEF probability. Resting PCWP increased progressively with higher HFpEF probability (P< 0.0001), and patients with group 1 PH and high HFpEF probability had the greatest increases in PCWP with nitric oxide, fluid challenge, and exercise (P< 0.001 for all), changes that were comparable to patients with HFpEF with no pulmonary vascular disease (n=194), but lower than those with HFpEF and combined precapillary and postcapillary PH. Left ventricular/atrial size, diastolic function, quality of life, 6-minute walk distance, and peak VO2 were most abnormal in patients with group 1 PH and high HFpEF probability compared with those with low or intermediate HFpEF probability (P< 0.0001 for all). Increasing HFpEF probability in group 1 PH was associated with greater risk of death (HR per decile of HFpEF probability 1.09; 95%CI: 1.05-1.13; P < 0.0001). Quantifying pretest probability for HFpEF in patients with group 1 PH identifies a subset of patients with worse dynamic PCWP response indicative of subclinical left heart disease, with poorer functional status, quality of life, and survival. Further study in this group 1 PH subgroup is indicated to determine whether PH therapies are effective and safe, and also whether HFpEF-specific therapies can improve functional status and outcomes.

Diagnostic and therapeutic practice for HFpEF across continents and regions: An international survey.

This study aims to evaluate the worldwide variations in the diagnosis and treatment of heart failure with preserved ejection fraction (HFpEF), using an HF survey distributed internationally to physicians, including both cardiologists and non-cardiologists. A group of HF specialists designed an independent, academic web-based survey focusing on HFpEF care and diagnosis, which was distributed via scientific societies and various social networks between 1 May 2023 and 1 July 2023. The survey included 1459 physicians (1242 cardiologists and 217 non-cardiologists) from 91 countries, with a mean age of 42 (34-49) years and 61% male. Most physicians (89.2%) defined HFpEF as left ventricular ejection fraction ≥50%. Significant regional variations were observed in HFpEF management (P<0.001 for all comparisons unless stated otherwise). Cardiologists managed 63.1% of HFpEF patients overall, with significant variability across regions (P < 0.001). The estimated HFpEF prevalence was highest in Eastern Asia and Western Europe and lowest in Africa and South America. Diagnostic practices varied: natriuretic peptide use ranged from 70%-74% in Africa to 95%-97% in Southern/Western Europe. Echocardiographic parameters showed regional differences, with diastolic stress testing used most in South-Eastern Asia (47% vs. 13-36% elsewhere). HFpEF scoring systems were most common in South-Eastern Asia (78%) and least in Africa (30.1%). Coronary artery disease screening approaches differed, with Eastern Asian physicians more likely to always perform routine angiograms (52%) compared with Northern Europeans (12%). Treatment preferences also varied regionally. Sodium glucose co-transporter-2 inhibitors (SGLT2i) was the preferred first-line treatment (45%-70% across regions), followed by diuretics. In an ideal setting, 52% would primarily use SGLT2i, 33% loop diuretics, and 22% beta-blockers. Drug availability differed significantly: SGLT2i was most available (88% overall), while ARNI was least available (61%). South America and Middle Eastern/Northern Africa reported lower availability of guideline-directed therapies. Multidisciplinary HF programmes were most common in Asia (70%) and least in Africa (24%). The perceived benefit of atrial flow regulator devices also showed significant regional differences. There are considerable global variations in the diagnosis and management of HFpEF. Most physicians favour SGLT2i despite regional disparities in health care resources and guideline adherence. Harmonized practices and improved access to comprehensive care can enhance outcomes of HFpEF patients worldwide.

Association of systemic inflammatory markers with clinical adverse prognosis and outcomes in HFpEF: a systematic review and meta-analysis of cohort studies.

To evaluate the association between systemic inflammatory markers and clinical outcomes (all-cause mortality, cardiovascular mortality, and rehospitalization) in patients with heart failure with preserved ejection fraction (HFpEF). We conducted a comprehensive literature search in PubMed, Embase, and Ovid Medline databases from inception to June 27, 2024. Studies were included if they were observational clinical studies involving HFpEF patients over 18 years old, with exposure to systemic inflammatory markers and reporting on adverse prognosis outcomes. The Newcastle-Ottawa Scale (NOS) was used to assess study quality. Eight studies ultimately included in the meta-analysis which involved 9,744 participants from six countries. The meta-analysis showed that systemic inflammatory markers were significantly associated with all-cause mortality (HR 1.43, 95% CI 1.19-1.72, p < 0.05), cardiovascular mortality (HR 2.04, 95% CI 1.33-3.12, p < 0.05), and cardiovascular rehospitalization (HR 2.83, 95% CI 0.92-8.67, p < 0.05) in HFpEF patients. Low heterogeneity was observed across studies (I2 = 0.00%). Sensitivity and publication bias analyses indicated that the results were robust. Systemic inflammatory markers demonstrate significant predictive value for adverse clinical outcomes in HFpEF patients. The findings suggest that monitoring systemic inflammation may provide valuable prognostic information for clinicians managing HFpEF patients. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=562698, identifier (CRD42024562698).

Prevalencia de amiloidosis cardiaca por transtirretina en pacientes con insuficiencia cardiaca y fracción de eyección conservada: estudio PRACTICA

Introduction and objectivesTransthyretin cardiac amyloidosis (ATTR-CA) is a frequent cause of heart failure with preserved ejection fraction (HFpEF). This study sought to determine the prevalence of ATTR-CA among HFpEF patients in a multicenter nationwide study. MethodsConsecutive ambulatory or hospitalized patients aged ≥50 years with HFpEF and left ventricle hypertrophy ≥12mm were studied at 20 Spanish hospitals. Screening for cardiac amyloidosis was initiated according to the usual clinical practice of each center. Positive scintigraphs were centrally analyzed. Results422 patients were included, of whom 387 underwent further screening for cardiac amyloidosis. A total of 65 patients (16.8%) were diagnosed with ATTR-CA, none below 75 years. There was an increase of prevalence with age. Of them, 60% were male, with a mean age of 85.3±5.2 years, mean left ventricle ejection fraction of 60.3±7.6% and a mean maximum left ventricle wall thickness of 17.2 [12-25] mm. Most of the patients were New York Heart Association class II (48.4%) or III (46.8%). Besides being older than non-ATTR-CA patients, ATTR-CA patients had higher median NT-proBNP levels (3801 [2266-7132] vs 2391 [1141-4796] pg/mL; P=.003). There was no statistical difference in the prevalence of ATTR-CA by sex (19.7% for men and 13.8% for women, P=.085). A ∼7% (4/56) of the patients exhibited a genetic variant (ATTRv). ConclusionsThis multicenter nationwide study found a prevalence of 16.8%, confirming that ATTR-CA is a significant contributor to HFpEF in male and female patients with left ventricle hypertrophy and more than 75 years.

Correlation of serum homocysteine and cystatin C levels with prognosis in heart failure with preserved ejection fraction patients

ObjectiveThis study investigated the relationship of serum homocysteine (Hcy) and cystatin C (Cys C) levels with the prognosis of patients with heart failure with preserved ejection fraction (HFpEF).MethodsA total of 178 patients with HFpEF who were admitted to our hospital between December 2019 and November 2020 were included. Patients were grouped based on their serum Hcy and Cys C levels: high Hcy level, normal Hcy level, high Cys C level, and normal Cys C level. Cardiac function, ventricular remodeling indices, and prognosis were compared among patients in these groups. Additionally, the predictive value of serum Hcy and Cys C levels for adverse cardiovascular events in HFpEF patients was analyzed.ResultsPatients’ mean age in the high Hcy level, normal Hcy level, high Cys C level, and normal Cys C level groups was 69.21 ± 4.17,67.74 ± 4.28,69.95 ± 4.98, and 67.06 ± 4.13 years old, respectively. The high Hcy level group exhibited a lower proportion of class II cardiac function according to the New York Heart Association (NYHA) classification and a higher proportion of class IV cardiac function than the normal Hcy level group, with statistically significant differences. Similarly, the high Cys C level group had a lower proportion of class II cardiac function and a higher proportion of class IV cardiac function compared with the normal Cys C level group, with statistically significant differences. Left ventricular end-diastolic internal diameter (LVEDD), left ventricular end-systolic internal diameter (LVESD), and left ventricular mass index (LVMI) were significantly higher in both the high Hcy level and high Cys C level groups compared with the normal group, with statistically significant differences. The rates of all-cause mortality and class I endpoint events were significantly higher in the high Hcy level and high Cys C level groups than in the normal group. Multifactorial logistic regression analysis demonstrated that adverse cardiovascular events were significantly associated with cardiac function class, LVEDD, LVESD, LVMI, Hcy, and Cys C in patients with HFpEF. The area under the curve (AUC) values for Hcy and Cys C, determined using receiver operating characteristic (ROC) curve analysis, were 0.778 (optimal critical value, 25.38) and 0.681 (optimal critical value, 1.56), respectively, for predicting adverse cardiovascular events. Both Hcy and Cys C serum levels were positively correlated with LVEDD, LVESD, LVMI, and NYHA classification.ConclusionSerum levels of Hcy and Cys C were closely associated with cardiac function, ventricular remodeling indices, and prognosis in patients with HFpEF. These levels may serve as valuable indices for assessing HFpEF patients’ health status and prognosis, providing important insights into their potential role as biomarkers for HFpEF management and prognosis.

Heart Failure with Preserved Ejection Fraction Correlates with Fibrotic Atrial Myopathy in Patients Undergoing Atrial Fibrillation Ablation.

Background: The incidence of atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) is high. Impaired left atrial (LA) function is a major determinant in HFpEF. However, the extent of electrical LA tissue degeneration in HFpEF is unknown. Therefore, we sought to investigate the amount of arrhythmogenic and fibrotic LA tissue degeneration in HFpEF patients presenting for AF ablation. Methods: We prospectively screened consecutive patients presenting for first time AF ablation. The HFA-PEFF score was used to identify HFpEF patients. Bipolar high-density voltage mapping was created in sinus rhythm prior to ablation to evaluate the general LA bipolar voltage and quantify areas of low voltage. LVAs were defined as areas with bipolar voltage < 0.5 mV. Results: In total, 187 patients were prospectively enrolled (age 65 ± 11 years, 45% female, 46% persistent AF, 25% HFpEF) in this study. HFpEF patients were older and had a higher CHA2DS2-VASc score (70 ± 9 vs. 63 ± 11 years and 3.2 ± 1.5 vs. 2.3 ± 1.5, each p < 0.001, respectively). Overall, low-voltage areas (LVAs) were present in 97 patients (52%), whereas 76% of the HFpEF population had LVA, as compared to 44% of patients without HFpEF (p < 0.001). HFpEF was associated with generally decreased LA bipolar voltage (1.09 ± 0.64 vs. 1.83 ± 0.91 mV; p < 0.001) and predictive of the presence of low-voltage areas (76% vs. 44% p < 0.001). The HFA-PEFF score inversely correlated with LA bipolar voltage (=-0.454; p < 0.001). Conclusions: HFpEF closely relates to generally decreased LA bipolar voltage and to the existence of fibrotic and arrhythmogenic LA tissue degeneration.

Single-cell transcriptomics reveal distinctive patterns of fibroblast activation in heart failure with preserved ejection fraction

AbstractInflammation, fibrosis and metabolic stress critically promote heart failure with preserved ejection fraction (HFpEF). Exposure to high-fat diet and nitric oxide synthase inhibitor N[w]-nitro-l-arginine methyl ester (L-NAME) recapitulate features of HFpEF in mice. To identify disease-specific traits during adverse remodeling, we profiled interstitial cells in early murine HFpEF using single-cell RNAseq (scRNAseq). Diastolic dysfunction and perivascular fibrosis were accompanied by an activation of cardiac fibroblast and macrophage subsets. Integration of fibroblasts from HFpEF with two murine models for heart failure with reduced ejection fraction (HFrEF) identified a catalog of conserved fibroblast phenotypes across mouse models. Moreover, HFpEF-specific characteristics included induced metabolic, hypoxic and inflammatory transcription factors and pathways, including enhanced expression of Angiopoietin-like 4 (Angptl4) next to basement membrane compounds, such as collagen IV (Col4a1). Fibroblast activation was further dissected into transcriptional and compositional shifts and thereby highly responsive cell states for each HF model were identified. In contrast to HFrEF, where myofibroblast and matrifibrocyte activation were crucial features, we found that these cell states played a subsidiary role in early HFpEF. These disease-specific fibroblast signatures were corroborated in human myocardial bulk transcriptomes. Furthermore, we identified a potential cross-talk between macrophages and fibroblasts via SPP1 and TNFɑ with estimated fibroblast target genes including Col4a1 and Angptl4. Treatment with recombinant ANGPTL4 ameliorated the murine HFpEF phenotype and diastolic dysfunction by reducing collagen IV deposition from fibroblasts in vivo and in vitro. In line, ANGPTL4, was elevated in plasma samples of HFpEF patients and particularly high levels associated with a preserved global-longitudinal strain. Taken together, our study provides a comprehensive characterization of molecular fibroblast activation patterns in murine HFpEF, as well as the identification of Angiopoietin-like 4 as central mechanistic regulator with protective effects.

Efficacy of Sodium-Glucose 2 Transporter Inhibitors in Heart Failure With Preserved Ejection Fraction: A Narrative Review.

Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent condition. It occurs more commonly in older patient populations with multiple comorbidities, such as hypertension, diabetes, and obesity. However, managing HFpEF has been challenging due to its complex pathophysiology, and medications effective for heart failure with reduced ejection fraction (HFrEF) have not shown similar efficacy in HFpEF. Sodium-glucose 2 transporter (SGLT2) inhibitors were originally developed for the treatment of type 2 diabetes mellitus, yet several trials and papers have proved their significant role in HFpEF. Through a variety of mechanisms, including natriuresis, diuresis, and anti-inflammatory effects, to name a few, this class of drugs has shown promising results in HFpEF patients. The use of SGLT2 inhibitors in HFpEF has resulted in improvements in several aspects, including biomarkers, imaging, symptomatology, and mortality. Moreover, SGLT2 inhibitors have a favorable safety profile, which is especially significant given the high comorbidity burden in HFpEF patients. This feature is particularly notable given the type of patient being managed. Extensive research is still being undertaken for their use in HFpEF, given the positive results obtained thus far.

Beyond weight loss: the potential of glucagon-like peptide-1 receptor agonists for treating heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various phenotypes, and obesity is one of the most common and clinically relevant phenotypes of HFpEF. Obesity contributes to HFpEF through multiple mechanisms, including sodium retention, neurohormonal dysregulation, altered energy substrate metabolism, expansion of visceral adipose tissue, and low-grade systemic inflammation. Glucagon-like peptide-1 (GLP-1) is a hormone in the incretin family. It is produced by specialized cells called neuroendocrine L cells located in the distal ileum and colon. GLP-1 reduces blood glucose levels by promoting glucose-dependent insulin secretion from pancreatic β cells, suppressing glucagon release from pancreatic α cells, and blocking hepatic gluconeogenesis. Recent evidence suggests that GLP-1 receptor agonists (GLP-1 RAs) can significantly improve physical activity limitations and exercise capacity in obese patients with HFpEF. The possible cardioprotective mechanisms of GLP-1 RAs include reducing epicardial fat tissue thickness, preventing activation of the renin-angiotensin-aldosterone system, improving myocardial energy metabolism, reducing systemic inflammation and cardiac oxidative stress, and delaying the progression of atherosclerosis. This review examines the impact of obesity on the underlying mechanisms of HFpEF, summarizes the trial data on cardiovascular outcomes of GLP-1 RAs in patients with type 2 diabetes mellitus, and highlights the potential cardioprotective mechanisms of GLP-1 RAs to give a pathophysiological and clinical rationale for using GLP-1 RAs in obese HFpEF patients.

Clinical characteristics and prognostic impact of atrial fibrillation among older patients with heart failure with preserved ejection fraction hospitalized for acute heart failure.

Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are often coexisting conditions, but their interrelationship has not yet been clarified. This study investigated the clinical characteristics and prognostic impact of AF among older patients with HFpEF hospitalized for acute HF (AHF). The study included patients 65years of age and older who were admitted to the Emergency Department due to AHF from 1 January 2016 to 31 December 2019. Patients were divided into two groups according to the presence of AF. The primary endpoint was all-cause, in-hospital mortality. Overall, 770 patients with HFpEF were included, mean age 82years, 53% were females. Nearly, a third (30%) of these patients had a concomitant AF and they were significantly older and had higher N-Terminal pro-B-type natriuretic peptide (NT-proBNP) values. Overall, the in-hospital mortality rate was much higher among HFpEF patients with AF compared to those without AF (11.4% vs 6.9%, respectively; p = 0.037). At multivariate analysis, AF emerged as an independent risk factor for death (OR 1.73 [1.03-2.92]; p = 0.038). Among older patients with HFpEF admitted for AHF, the coexistence of AF was associated with a nearly twofold increased risk of all-cause in-hospital mortality. Patients with HFpEF and AF describe a phenotype of older and more symptomatic patients, with higher NT-proBNP, left atrial enlargement, right ventricular dysfunction, and higher CV mortality.

P144 PHENOTYPIC CHARACTERISATION OF HEART FAILURE WITH PRESERVED EJECTION FRACTION ACCORDING TO BODY MASS INDEX: SUBANALYSIS OF THE ARGENTINE ARFEY-PRESER REGISTRY

Background: Nutritional status, characterised by body mass index (BMI), may influence therapeutic decisions in heart failure with preserved ejection fraction (HFpEF). The objectives of this study were to identify clinical and echocardiographic characteristics associated with nutritional status and to analyse therapeutic strategies in HFpEF patients in Argentina. Materials and Methods: This prospective, multicentre observational registry enrolled outpatients or those discharged from hospitals, with prior informed consent. The study spanned from December 2022 to February 2024. Inclusion criteria were: 1) presence of current signs and symptoms, LVEF ≥50%, 2) structural heart disease with LVH, LAE, or average E/e’ ≥15 on Doppler, 3) elevated natriuretic peptides: sinus rhythm: NTproBNP &gt;125 pg/ml or BNP &gt;35 pg/ml; Atrial fibrillation/flutter: NTproBNP &gt;375 pg/ml or BNP &gt;105 pg/ml; and 5) commitment to 6-month and 1-year follow-ups. Exclusion criteria comprised: 1) acute coronary syndrome, 2) coronary artery bypass grafting, or valve replacement within the preceding 3 months, 3) confirmed infiltrative or hypertrophic cardiomyopathy, severe valvular disease, 4) severe illness with &lt;1-year prognosis, and chronic renal failure on permanent dialysis. Results: A total of 449 patients were enrolled, with 440 having available BMI data for this analysis. Patient enrolment was consistent across centres and nationwide. BMI analysis revealed 0.7% undernutrition, 16.6% normal weight, 32% overweight, and 50.7% obesity. In Figure1 showed the analysis of clinical, laboratory, echocardiographic, and HF severity variables according to BMI. Significant differences were found in treatment, with lower use of RAS inhibitors and beta-blockers in non-normal weight patients compared to those with overweight and obesity. Conclusions: For a similar HFpEF severity profile, the phenotype according to BMI suggests different clinical characteristics. Underweight/normal weight patients were older, with more LAE and pulmonary hypertension, and fewer risk factors. Obesity was present in half of the cases, characterised by younger patients with a high burden of cardiovascular risk factors. This impacts the use of certain heart failure medications.

Abstract P124: Prognostic Significance of Free Triiodothyronine Levels in Patients with Heart Failure with Preserved Ejection Fraction and Hypertrophic Cardiomyopathy: A Multicenter Retrospective Analysis

Objective: This study aimed to identify key prognostic factors in patients with hypertrophic cardiomyopathy (HCM) presenting heart failure with preserved ejection fraction (HFpEF), with a special focus on the role of Free Triiodothyronine (FT3) levels. Methods: A retrospective cohort study was conducted, comprising HFpEF patients admitted to two medical centers from 2009 to 2019. Data collection included demographic and clinical parameters, particularly FT3 levels. Univariate and multivariate Cox analyses, Kaplan-Meier (KM) survival curve analysis, and Restricted Cubic Spline (RCS) curve analysis were employed to identify prognostic factors and to assess the non-linear predictive value of FT3. Results: The analysis revealed that age, atrial fibrillation, and NT-proBNP levels significantly influenced prognosis in heart failure patients. Additionally, FT3 levels emerged as a significant independent predictor of both all-cause mortality and cardiac transplantation. Patients with lower FT3 levels exhibited poorer long-term prognoses, with 2.885 identified as the critical FT3 value. Conclusions: These findings underscore the importance of FT3 levels as a crucial prognostic factor in patients with heart failure, warranting consideration in patient outcomes assessments. Clinicians are recommended to monitor FT3 levels and contemplate interventions aimed at maintaining or enhancing thyroid function in these patients to improve outcomes.