Image-Based Estimation of Left Ventricular Myocardial Stiffness.

Elevation in left ventricular (LV) myocardial stiffness is a key remodeling-mediated change that underlies the development and progression of heart failure (HF). Despite the potential diagnostic value of quantifying this deterministic change, there is a lack of enabling techniques that can be readily incorporated into current clinical practice. To address this unmet clinical need, we propose a simple protocol for processing routine echocardiographic imaging data to provide an index of left ventricular myocardial stiffness, with protocol specification for patients at risk for heart failure with preserved ejection fraction. We demonstrate our protocol in both a preclinical and clinical setting, with representative findings that suggest sensitivity and translational feasibility of obtained estimates.

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

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Finerenone in Patients With a Recent Worsening Heart Failure Event: The FINEARTS-HF Trial.

BACKGROUND: Patients with heart failure (HF) and a recent worsening heart failure (WHF) event are known to be at high risk of recurrent hospitalization and death, regardless of ejection fraction. OBJECTIVES: This study examined the efficacy and safety of the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone in relation to the recency of a WHF event. METHODS: FINEARTS-HF (FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure) was a randomized, double-blind, placebo-controlled trial of finerenone in patients with HF and left ventricular ejection fraction ≥40%. In this prespecified analysis, we assessed the risk of cardiovascular (CV) events and response to finerenone vs placebo in relation to the time from WHF to randomization (during or within 7 days, 7 days to 3 months, >3 months, or no prior WHF). The primary outcome was a composite of total (first and recurrent) WHF events and CV death, analyzed using a proportional rates method. RESULTS: Of 6,001 patients validly randomized to finerenone or placebo, 1,219 (20.3%) were enrolled during (749 [12.5%]) or within 7 days (470 [7.8%]), 2,028 (33.8%) between 7 days and 3 months, and 937 (15.6%) >3 months from a WHF event; 1,817 (30.3%) had no prior history of WHF. Rates of the primary composite outcome varied inversely with time since WHF, with >2-fold higher risk in those enrolled during or within 7 days of WHF compared with those enrolled >3 months from WHF or without prior WHF (risk ratio [RR]: 2.13; 95% CI: 1.82-2.55). Compared to placebo, finerenone appeared to lower the risk of the primary composite to a greater extent in those enrolled within 7 days of WHF (RR: 0.74; 95% CI: 0.57-0.95) or between 7 days and 3 months of WHF (RR: 0.79; 95% CI: 0.64-0.97) than in those >3 months from WHF or without prior WHF (RR: 0.99; 95% CI: 0.81-1.21); however, no definitive treatment-by-time interaction could be confirmed (P = 0.07). Greater absolute risk reductions with finerenone were accordingly seen in those with recent WHF (Ptrend = 0.011). The risk of adverse events including hyperkalemia and worsening renal function among patients assigned to finerenone was not increased in those with recent WHF. CONCLUSIONS: Compared with those without recent WHF, patients with HF and mildly reduced or preserved ejection fraction who have experienced a recent WHF event are at higher risk for recurrent HF events and CV death; a possible signal of enhanced absolute treatment benefit with finerenone in this population requires further confirmation in future studies. (Study to Evaluate the Efficacy [Effect on Disease] and Safety of Finerenone on Morbidity [Events Indicating Disease Worsening] & Mortality [Death Rate] in Participants With Heart Failure and Left Ventricular Ejection Fraction [Proportion of Blood Expelled Per Heart Stroke] Greater or Equal to 40% [FINEARTS-HF], NCT04435626; A study to gather information on the influence of study drug finerenone on the number of deaths and hospitalizations in participants with heart failure EudraCT 2020-000306-29).

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.

Gender-specific risks for incident cancer in patients with different heart failure phenotypes.

BACKGROUND: There is conflicting evidence regarding whether heart failure (HF) increases the risk of developing cancer. OBJECTIVE: This study aimed to assess the association between HF and incident cancer, considering gender differences and HF phenotypes. METHODS: This retrospective study was conducted on data of adult individuals, free of cancer at baseline, from the First Affiliated Hospital of Wenzhou Medical University between January 2009 and February 2023. The patients with HF were categorized as HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). The primary outcome was incident cancer, including obesity-related, tobacco-related, lung, colorectal and breast cancers. RESULTS: Of 33 033 individuals enrolled, 16 722 were diagnosed with HF, including 10 086 (60.3%) with HFpEF and 6636 (39.7%) with HFrEF. During a median follow-up period of 4.6 years (inter-quartile range: 2.6-7.3), incident cancer was diagnosed in 10.5% (1707 patients) of the non-HF group and 15.1% (2533 individuals) of the HF group. After adjusting for potential confounding factors, patients with HF had a 58% increased risk of cancer than those without HF [adjusted hazard ratio (HR) 1.58, 95% confidence interval (CI) 1.48-1.69, P < 0.001]. This risk was consistent across genders (female: adjusted HR 1.95, 95% CI 1.74-2.18, P < 0.001; male: adjusted HR 1.41, 95% CI 1.30-1.54, P < 0.001) and HF phenotypes (HFpEF: adjusted HR 1.69, 95% CI 1.57-1.81, P < 0.001; HFrEF: adjusted HR 1.32, 95% CI 1.20-1.46, P < 0.001). CONCLUSIONS: Both HFpEF and HFrEF are associated with an increased risk of incident cancer. This correlation maintains its validity across genders.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: In HFpEF, there is a more intensified iNOS overexpression, while in HFrEF, ER stress is more prominent.

Construction of a metabolism-malnutrition-inflammation prognostic risk score in patients with heart failure with preserved ejection fraction: a machine learning based Lasso-Cox model.

BACKGROUND: Metabolic disorder, malnutrition and inflammation are involved and interplayed in the mechanisms of heart failure with preserved ejection fraction (HFpEF). We aimed to construct a Metabolism-malnutrition-inflammation score (MIS) to predict the risk of death in patients with HFpEF. METHODS: We included patients diagnosed with HFpEF and without infective or systemic disease. 20 biomarkers were filtered by the Least absolute shrinkage and selection operator (Lasso)-Cox regression. 1000 times bootstrapping datasets were generated to select biomarkers that appeared above 95% frequency in repetitions to construct the MIS. RESULTS: Among 1083 patients diagnosed with HFpEF, 342 patients (31.6%) died during a median follow-up period of 2.5 years. The MIS was finally constructed based on 6 biomarkers, they were albumin (ALB), red blood cell distribution width-standard deviation (RDW-SD), high-sensitivity C-reactive protein (hs-CRP), lymphocytes, triiodothyronine (T3) and uric acid (UA). Incorporating MIS into the basic predictive model significantly increased both discrimination (∆C-index = 0.034, 95% CI 0.013-0.050) and reclassification (IDI, 6.6%, 95% CI 4.0%-9.5%; NRI, 22.2% 95% CI 14.4%-30.2%) in predicting all-cause mortality. In the time-dependent receiver operating characteristic (ROC) analysis, the mean area under the curve (AUC) for the MIS was 0.778, 0.782 and 0.772 at 1, 3, and 5 years after discharge in the cross-validation sets. The MIS was independently associated with all-cause mortality (hazard ratio: 1.98, 95% CI [1.70-2.31], P < 0.001). CONCLUSIONS: A risk score derived from 6 commonly used inflammatory, nutritional, thyroid and uric acid metabolic biomarkers can effectively identify high-risk patients with HFpEF, providing potential individualized management strategies for patients with HFpEF.

Imaging Advances in Heart Failure.

This paper delves into the significance of imaging in the diagnosis, aetiology and therapeutic guidance of heart failure, aiming to facilitate early referral and improve patient outcomes. Imaging plays a crucial role not only in assessing left ventricular ejection fraction, but also in characterising the underlying cardiac abnormalities and reaching a specific diagnosis. By providing valuable data on cardiac structure, function and haemodynamics, imaging helps diagnose the condition, evaluate haemodynamic status and, consequently, identify the underlying pathophysiological phenotype, as well as stratifying the risk for outcomes. In this article, we provide a comprehensive exploration of these aspects.

Drug-induced increase in dispersion of ventricular repolarization in patients with heart failure with preserved ejection fraction.

BACKGROUND: Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with enhanced response to drug-induced QT interval lengthening. We determined the influence of HFpEF on drug-induced lengthening of dispersion of repolarization, a measure of proarrhythmic risk. METHODS: We administered intravenous ibutilide 0.003 mg/kg to 10 patients with HFpEF and 10 age- and sex-matched controls without HF. 12­lead electrocardiograms were obtained prior to, during, and serially for 8 h post-ibutilide. Tpeak-Tend, a measure of dispersion of ventricular repolarization, and heart rate-corrected J-Tpeak, representing early repolarization, were measured by an investigator blinded to study groups. RESULTS: Baseline (pre-ibutilide) Tpeak-Tend and J-Tpeakc were not significantly different in the HFpEF and control groups. Maximum Tpeak-Tend was longer in the HFpEF group than in the control group (85 ±â€¯10 vs 73 ±â€¯8 ms, p = 0.01). Additionally, % change from baseline in Tpeak-Tend was longer in the HFpEF group [median (IQR) 17 (11) vs 8 (3)%, p = 0.03]. The area under the effect curve (AUEC) for Tpeak-Tend was also larger in the HFpEF group (600 ±â€¯42 vs. 543 ±â€¯49 ms•hr, p = 0.03). Maximum J-Tpeakc, % change from baseline in J-Tpeakc and AUEC for J-Tpeakc in the two groups were not significantly different. CONCLUSION: HFpEF is associated with enhanced response to drug-induced increases in dispersion of repolarization.

Association between triglyceride glycemic index and ejection fraction preserved heart failure in hypertensive patients.

Background: The triglyceride-glucose (TyG) index is regarded as an independent predictor of cardiovascular disease consequences and a reliable surrogate measure of insulin resistance (IR). However, the correlation analysis between triglyceride glucose index and heart failure with preserved ejection fraction in patients with essential hypertension remains unknown. Methods: A single-center, retrospective study was conducted with patients diagnosed with essential hypertension at the First Affiliated Hospital of Xinjiang Medical University, from December 2018 to September 2020. Participants were selected based on specific inclusion and exclusion criteria, with their clinical data and laboratory tests collected. The study employed Spearman's correlation analysis, logistic regression models, restricted cubic spline plots, and receiver operating characteristic (ROC) curves to investigate the relationships between the TyG index and HFpEF. Results: Out of 1,602 enrolled hypertensive patients, 992 were included in the analysis after applying exclusion criteria. Patients were categorized into tertiles based on the TyG index, which showed that patients in the highest tertile had characteristics associated with a higher risk of HFpEF, including age, body mass index (BMI), systolic blood pressure (SBP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and left ventricular mass index (LVMI). A significant, independent association between the TyG index and HFpEF was confirmed, with an odds ratio (OR) of 5.127 (95% CI [3.894-6.856]). Furthermore, an S-shaped nonlinear relationship was observed between the TyG index and the incidence of HFpEF (nonlinear p < 0.001). TyG index (AUC: 0.824, 95% CI [0.795-0.854]), NT-proBNP (AUC: 0.840, 95% CI [0.816-0.864]), and LVMI (AUC: 0.847, 95% CI [0.820-0.875]) showed good predictive ability for HFpEF. In addition, the TyG+LVMI combination demonstrated the strongest predictive ability (AUC: 0.907, 95% CI [0.887-0.927]). Conclusion: The study underscores a significant association between IR, as indicated by the TyG index, and the development of HFpEF in hypertensive patients. It highlights the critical role of metabolic dysfunction in the pathophysiology of HFpEF, advocating for a broader perspective on cardiovascular risk management.

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.

Stress Echocardiography for Assessment of Diastolic Function.

PURPOSE OF REVIEW: Diastolic dysfunction is an important, though often underappreciated, cause for exertional dyspnea. Echocardiography enables noninvasive evaluation of diastolic function and filling pressure, but images acquired at rest may be insensitive for detection of exertional abnormalities. This review focuses on stress echocardiography to assess diastolic function, including traditional and novel techniques, with emphasis on specific patient sub-groups in whom this testing may be valuable. RECENT FINDINGS: Emerging data informs patient selection for diastolic stress testing. Further, increasing literature provides considerations for performance and interpretation of diastolic metrics relevant to patients with heart failure with preserved ejection fraction, hypertrophic cardiomyopathy, athletes, and those with microvascular coronary dysfunction. Methods, such as speckle-tracking and multi-modality imaging, provide additional and complementary information for non-invasive diastolic assessment. This review serves as a guide to optimally utilize existing and novel techniques of stress echocardiography for diastolic assessment across a broad range of patients.

Cardiac structural and functional changes in OSAHS patients with heart failure with preserved ejection fraction and atrial fibrillation.

OBJECTIVE: To explore the cardiac structural and functional changes in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients with heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF). METHODS: This retrospective study included 336 OSAHS patients with HFpEF. They were divided into Groups A (without an AF history and no AF episodes during cardiac color ultrasound examination), B (an AF history but no AF episodes), and C (an AF history and AF episodes). They all received cardiac color ultrasound examinations. Cardiac structural and functional changes in ultrasonic cardiograms were compared between the three groups. RESULTS: Compared with Groups A and B, Group C showed increased left atrial diameter (LAD), left atrial volume (LAV), right ventricular diameter at end-diastole (RV-D1), right ventricular diameter at end-systole (RV-D2), right ventricular outflow tract diameter (RVOT2), right atrial diameter at end-diastole (RA-D1), right atrial diameter at end-systole (RA-D2), and right atrial area (RAA) (p < 0.05). Compared with Group A, Group C showed decreased fractional shortening (FS), left ventricular ejection fraction (LVEF), deceleration time (DT), isovolumic relaxation time (IVRT), E/E' ratio, and peak filling velocity (FPV), as well as increased E and E' (p < 0.01). Compared with Group B, Group C showed decreased FS and increased E and FPV (p < 0.01). CONCLUSION: In OSAHS patients with HFpEF and AF, cardiac remodeling and AF incidence are increased with the severity of OSAHS. OSAHS patients with HFpEF combined with AF have a significantly higher abnormality rate in right heart structural indices rather than left heart, mainly in the right atrium.

Long-term Glycemic Variability Predicts Adverse Outcomes in Diabetic Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Previous studies have shown associations between glycemic variability (GV) and cardiovascular outcomes in patients with type 2 diabetes. However, the impact of GV on outcomes in patients with heart failure with preserved ejection fraction (HFpEF) has not been investigated. METHOD: Between 2014 and 2019, we conducted a retrospective cohort analysis using the electronic medical records of a tertiary medical center in Taiwan. Diabetic patients with HFpEF were enrolled. Each individual's coefficient of variability of fasting glucose (FGCV) was determined and the FGCVs were categorized into tertiles. Multivariable Cox regression models and the Kaplan-Meier with log-rank test were used to assess the association between the FGCV and the risk of hospitalization for heart failure (HHF), atrial fibrillation (AF), cardiovascular mortality, and overall mortality. RESULTS: In a cohort comprising 74,835 individuals diagnosed with diabetes, a subset of 753 patients was identified with HFpEF and measurement of FGCV. The median follow-up duration 38.1 months. In the model of full adjustment, the third FGCV tertile was significantly associated with an increased risk of HHF compared to the first tertile (hazard ratio [HR] = 1.32, 95% confidence interval [CI] 1.04-1.69, p = 0.025). Likewise, the highest FGCV tertille was associated with an increased risk of death (HR 1.65, 95% CI: 1.16-2.35, p = 0.005) while it was not associated with increased of AF and cardiovascular mortality. Kaplan-Meier analyses revealed a significant association between FGCV and both HHF and overall mortality (log-rank p = 0.022 and <0.001, respectively). CONCLUSION: Our study highlights a significant association between increased GV and a higher incidence of HHF as well as an elevated overall mortality rate in individuals with diabetes and HFpEF.

Empagliflozin and other SGLT2 inhibitors in patients with heart failure and preserved ejection fraction: a systematic review and meta-analysis.

BACKGROUND: Heart failure (HF) is a highly prevalent disease, among the primary factors contributing to morbidity and death. One of its types is heart failure with preserved ejection fraction (HFpEF) comprising 40%-50% of newly diagnosed HF cases. Despite the high prevalence of HFpEF, there is still a lack of knowledge regarding the best drugs and treatment approaches to be used. However, the sodium-glucose co-transporter 2 (SGLT2) inhibitors could be a promising treatment. OBJECTIVES: To examine SGLT2 inhibitors' effect on hospitalization, cardiovascular death, and estimated glomerular filtration rate (eGFR) in HFpEF patients. SEARCH METHODS: We conducted searches for randomized controlled trials (RCTs) in PubMed, Embase, Scopus, and Web of Science up to July 2024. SELECTION CRITERIA: We chose RCTs that examined the effects of SGLT2 inhibitors and placebo in individuals with higher than 40% ejection fraction (HFpEF). DATA COLLECTION AND ANALYSIS: The methodology for the systematic review and meta-analysis was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. MAIN RESULTS: We included 8 studies with 16,509 participants. Drugs examined in our paper included empagliflozin, dapagliflozin, sotogliflozin, and ertugliflozin. Various outcomes were analyzed in different papers. However, different SGLT2 inhibitors lead to a decreased risk of cardiovascular hospitalization and kidney injury. Our meta-analysis showed a decreased risk of cardiovascular hospitalization but not death due to cardiovascular causes or other causes. These results were regardless of baseline status of eGFR, systolic blood pressure, atrial fibrillation or flutter, diabetes mellitus, sex, body mass index, and nt-proBNP. The included studies were of moderate to high quality. CONCLUSION: For individuals with HFpEF, SGLT2 inhibitors have been proven to be a safe and effective medication. However, more studies are needed for longer durations, reporting adverse events, effects on exercise tolerance, and other secondary outcomes.

Assessing Static Balance, Balance Confidence, and Fall Rate in Patients with Heart Failure and Preserved Ejection Fraction: A Comprehensive Analysis.

Chronic heart failure (CHF) is a complex clinical syndrome, associated with frailty, higher fall rates, and frequent hospitalizations. Heart Failure (HF) and preserved ejection fraction (HFpEF) is defined as a condition where a patient with HF have a diagnosis of left ventricular ejection fraction (LVEF) of ≥ 50%. The risk of HFpEF increases with age and is related to higher non-cardiovascular mortality. The aim of this study was to evaluate static balance and examine the effect of task difficulty on the discriminating power of balance control between patients with HFpEF (Patients with HFpEF) and their healthy controls. Moreover, the associations between static balance parameters, balance confidence, falls, lean muscle mass, and strength were assessed. Seventy two patients with HFpEF (mean age: 66.0 ± 11.6 years) and seventy two age- and gender-matched healthy individuals (mean age: 65.3 ± 9.5 years) participated in this study. Participants underwent a 30 s bilateral stance (BS) test and a 20 s Tandem-Romberg stance (TRS) on a force platform, evaluating the Range and Standard Deviation of Center of Pressure (COP) displacement parameters in both axes. Balance confidence was evaluated by the Activities-Specific Balance Confidence (ABC) Scale, and the number of falls during the last year was recorded. Lower limb strength was measured using an isokinetic dynamometer, isometric leg strength, and a Sit-to-Stand test. Bioelectrical impedance analysis was conducted to assess lean fat mass, lean fat mass index, and lean%. Patients with HFpEF presented with lower static balance in BS and TRS compared to healthy controls (p < 0.05), lower balance confidence by 21.5% (p < 0.05), and a higher incidence of falls by 72.9% (p < 0.05). BS was a better descriptor of the between-group difference. Furthermore, static balance, assessed in controlled lab conditions, was found to have little if no relationship to falls, strength, lean muscle mass, and balance confidence. Although no correlation was noted between the static balance parameters and falls, the fall rate was related to balance confidence, age, muscle strength, and lean fat.

Leukocyte Indices as Markers of Inflammation and Predictors of Outcome in Heart Failure with Preserved Ejection Fraction.

Background: The pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF) is suggested to be influenced by inflammation. Leukocyte indices, including the neutrophil-lymphocyte ratio (NLR), the monocyte-lymphocyte ratio (MLR), and the pan-immune inflammation value (PIV), can be utilized as biomarkers of systemic inflammation. Their prognostic utility is yet to be fully understood. Methods: Between December 2010 and May 2023, patients presenting to a tertiary referral center for HFpEF were included into a prospective registry. The association of the NLR, MLR, and PIV with the composite endpoint of all-cause mortality and HF-related hospitalization was tested utilizing Cox regression analysis. Results: In total, 479 patients (median 74.3, interquartile range (IQR): 69.22-78.3 years, 27.8% male) were included. Patients were observed for 43 (IQR: 11-70) months, during which a total of 267 (55.7%) patients met the primary endpoint. In a univariate Cox regression analysis, an above-the-median NLR implied a hazard ratio (HR) of 1.76 (95%-confidence interval (CI): 1.38-2.24, p < 0.001), an MLR of 1.46 (95%-CI: 1.14-1.86, p = 0.003), and a PIV of 1.67, 95%-CI: 1.30-2.13, p < 0.001) for the composite endpoint. After adjustment in a step-wise model, the NLR (HR: 1.81, 95%-CI: 1.22-2.69, p = 0.003), the MLR (HR: 1.57, 95%-CI: 1.06-2.34, p = 0.026), and the PIV (HR: 1.64, 95%-CI: 1.10-2.46, p = 0.015) remained significantly associated with the combined endpoint. Conclusions: The NLR, the MLR, and the PIV are simple biomarkers independently associated with outcomes in patients with HFpEF.

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

Objective: 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). Methods: 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. Results: 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. Conclusion: 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. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=562698, identifier (CRD42024562698).