Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common form of HF in older adults. While manifest as distinct clinical phenotypes, almost all patients with HFpEF will present with exercise intolerance or exertional dyspnea. Distinguishing HFpEF from other clinical conditions remains challenging, as the accurate diagnosis of HFpEF involves integrating a diverse array of cardiovascular (CV) structural and physiologic inputs. Owing to its intrinsic ability to characterize the structure and function of the myocardium, cardiac valves, pericardium, and vasculature, echocardiography (TTE) has emerged as an essential modality for diagnosing HFpEF. In contrast to HF with reduced EF, however, no single TTE variable defines HFpEF. Abnormal diastolic function is typically associated with HFpEF, but "diastolic dysfunction" per se is not synonymous with "HFpEF": the pathophysiology of HFpEF is more complex than diastolic dysfunction alone. HFpEF may involve abnormalities at multiple loci within the CV system, including (1) dysfunction of the left ventricle, left atrium, or right ventricle; (2) pulmonary hypertension or pulmonary vascular disease; (3) pericardial restraint; (4) abnormal systemic vascular impedance; (5) coronary or peripheral microcirculatory dysfunction; and (6) defects of tissue oxygen uptake within the periphery. Thus, the accurate diagnosis of HFpEF - and its specific clinical phenotypes - requires diagnostic algorithms that comprise multiple clinical variables, many of which may be derived from TTE data. Refining such algorithms to better discriminate among specific HFpEF phenotypes is the subject of continued investigation.

Left ventricular (LV) diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF) are common cardiac complications of patients with systemic sclerosis (SSc). Exercise stress echocardiography is often used in symptomatic patients with SSc to detect abnormal increases in pulmonary pressures during exercise, but the pathophysiologic and prognostic significance of exercise stress echocardiography to assess the presence of HFpEF in these patients is unclear.

Patients with SSc (n = 140) underwent ergometry exercise stress echocardiography with simultaneous expired gas analysis. The HFA-PEFF score ≥ 5 points was used to diagnose HFpEF. Thirty-five patients met the HFpEF criteria (prevalence 25%). Compared with patients with SSc-non-HFpEF, those with SSc-HFpEF were older and had a higher prevalence of coronary artery disease, more severe LV diastolic dysfunction (by definition), depressed right ventricular systolic function, reduced exercise capacity (lower peak oxygen consumption), and poorer ventilatory efficiency. Exercise right heart catheterization was performed in 25 patients and it confirmed elevated pulmonary capillary wedge pressure during peak exercise in patients with SSc-HFpEF. Participants were followed up to assess the primary composite endpoint: all-cause mortality, HF hospitalization, unplanned hospital visits requiring intravenous diuretics, or oral diuretic intensification. Compared with SSc-non-HFpEF, SSc-HFpEF had a 5.3-fold increased risk of the composite outcomes (hazard ratio 5.29, confidence intervals 2.06-13.5, P = 0.0005).

In addition to pulmonary haemodynamics, exercise stress echocardiography may be useful to identify the HFpEF phenotype that has different pathophysiology and clinical outcomes in patients with SSc.

Exercise stress echocardiography (ESE) is often used to identify heart failure with preserved ejection fraction (HFpEF) in patients presenting dyspnoea. However, diagnostic criteria have not been standardized. Here, we sought to develop ESE-based criteria to diagnose HFpEF in dyspnoeic patients.

A total of 81 consecutive patients with dyspnoea who underwent exercise right heart catheterization and ESE were evaluated. Diagnosis of HFpEF was ascertained by directly-measured haemodynamics (61 HFpEF and 20 controls). Logistic regression analysis was applied to develop an ESE-based scoring system to diagnose HFpEF. Multivariable logistic regression analysis identified resting left atrial reservoir strain < 20%, exercise septal E/e' ratio > 13, and increases in ultrasound B-lines as independent predictors of HFpEF. A weighted score was created with these variables (the ESE score) ranging from 0 to 5. The ESE score accurately discriminated HFpEF from controls [area under the curve (AUC) 0.90, P < 0.0001], with a superior diagnostic ability to the ASE/ESCVI criteria (AUC comparison P < 0.0001). The ESE score classified the HFpEF probability into three categories (probabilities: low risk 28%, intermediate risk 59-83%, and high risk 95-99%). In a cohort of 620 dyspnoeic patients, the predictive ability of the derived score was assessed. A higher ESE score was associated with an increased risk of all-cause mortality or worsening HF events even after adjusting for confounders (hazard ratio; 1.17 per 1-point increase, 95% confidence intervals; 1.00-1.37, P = 0.04).

The ESE score, which is based on three echocardiographic variables, may be an effective tool for diagnosing HFpEF on exercise echocardiography.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical diagnosis with a heterogeneous pathophysiology and clinical presentation. The hallmark of HFpEF is diastolic dysfunction associated with left ventricular remodeling and fibrosis. Myocardial interstitial fibrosis (MIF) occurs as the result of collagen deposition and is dependent on the underlying etiology of heart failure. Detection of MIF can be done by invasive histopathologic sampling or by imaging. More recently, novel biomarkers have been investigated as an alternative tool for not only the detection of MIF but also for the prognostication of patients with HFpEF which may in turn alleviate the need for invasive and expensive imaging in the future.

Plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) is commonly used to diagnose heart failure with preserved ejection fraction (HFpEF), but its diagnostic performance in the ambulatory/outpatient setting is unknown because previous studies lacked objective reference standards.

Among patients with chronic dyspnea, diagnosis of HFpEF or noncardiac dyspnea was determined conclusively by exercise catheterization in a derivation cohort (n=414), multicenter validation cohort 1 (n=560), validation cohort 2 (n=207), and a nonobese Japanese validation cohort 3 (n=77). Optimal NT-proBNP cut points for HFpEF rule out (optimizing sensitivity) and rule in (optimizing specificity) were derived and tested, stratified by obesity and atrial fibrillation. Derived cut points were tested in 3 additional validation cohorts (cohorts 4-6) in whom HFpEF was diagnosed by resting catheterization only (n=260), previous hospitalization for heart failure (n=447), or exercise echocardiography (n=517), respectively.

Current recommended rule-out NT-proBNP threshold <125 pg/mL had 82% sensitivity (95% CI, 77%-88%) with a body mass index (BMI) <35 kg/m2, decreasing to 67% (95% CI, 58%-77%) with a BMI ≥35 kg/m2. A lower rule-out NT-proBNP threshold <50 pg/mL displayed good sensitivity with a BMI <35 kg/m2 (97% [95% CI, 95%-99%]), with a modest decline in sensitivity with a BMI ≥35 kg/m2 (86% [95% CI, 79%-93%]); diagnostic thresholds were confirmed in validation cohorts 1 and 2 (91% [95% CI, 88%-95%] and 86% [95% CI, 80%-93%] with a BMI <35 kg/m2; 80% [95% CI, 74%-87%] and 84% [95% CI, 74%-93%] with a BMI ≥35 kg/m2). Current consensus age- and BMI-stratified rule-in thresholds demonstrated only 65% specificity (95% CI, 57%-72%). Rule-in NT-proBNP threshold ≥500 pg/mL had 85% specificity (95% CI, 78%-91%) with a BMI <35 kg/m2 (87% [95% CI, 80%-94%] and 90% [95% CI, 81%-99%] in validation cohorts), with 100% specificity at a BMI ≥35 kg/m2 (93% [95% CI, 81%-100%] and 100% in validation cohorts). With a BMI ≥35 kg/m2, lower rule-in thresholds (≥220 pg/mL) provided good specificity (88% [95% CI, 73%-100%]; 93% [95% CI, 81%-100%] and 100% in validation cohorts). Findings were consistent in validation cohorts 3 through 6 (sensitivity of <50 pg/mL, 93%-98%; specificity of ≥500 pg/mL, 82%-89%). NT-proBNP provided no incremental discrimination among patients with history of AF; ≥98% of patients with AF and dyspnea were found to have HFpEF in our cohorts.

In patients with chronic unexplained dyspnea, current rule-in and rule-out NT-proBNP diagnostic thresholds lead to unacceptably high error rates, with important interactions by obesity and AF status. In our study, NT-proBNP provided little value in those with AF and dyspnea because the presence of AF is by itself a robust biomarker of HFpEF. Use of separate rule-in and rule-out diagnostic thresholds stratified by BMI reduces miscategorization and can guide more appropriate use of exercise testing for possible HFpEF.

Heart failure with preserved ejection fraction (HFpEF) remains underdiagnosed in primary care settings, where echocardiography is not available. This study aimed to develop and validate a scoring system that does not include echocardiographic variables for HFpEF screening among patients with shortness of breath.

A total of 622 consecutive patients referred for exercise stress echocardiography were evaluated (283 HFpEF and 339 controls). Diagnosis of HFpEF was determined by the HFA-PEFF algorithm Steps 2-3.

Multivariable logistic regression analysis identified age ≥65 years, coronary artery disease, elevated natriuretic peptide levels, anemia, cardiomegaly on chest radiography, and left ventricular high-voltage on electrocardiogram as independent predictors of having HFpEF. A weighted score, including the six predictors and atrial fibrillation, was created (BREATH2 score). The BREATH2 score accurately discriminated HFpEF from controls [area under the curve (AUC) 0.84, p < 0.0001], with a superior diagnostic ability to the H2FPEF score. The diagnostic accuracy was confirmed in an external validation cohort (n = 105, AUC 0.78, p < 0.0001) and in patients whose diagnosis was determined by exercise right heart catheterization (n = 79, AUC 0.75, p = 0.0001). The BREATH2 score classified each patient into different risk categories of having HFpEF, ranging from 4 % to 93 %.

The BREATH2 score can be an effective screening tool in primary care settings to help refer patients to a secondary hospital for further evaluation.

Unexplained exertional dyspnoea without significant elevation of natriuretic peptides is common. One of the causes might be early heart failure with preserved ejection fraction (HFpEF).

This study aimed to characterize patients with exertional dyspnoea and normal/near-to-normal N-terminal pro-brain natriuretic peptide (NT-proBNP) levels with regard to early stages of HFpEF and non-cardiac causes.

Sixty-six patients (age 62 ± 7 years old, 85% women) with dyspnoea assessed using the Multidimensional Dyspnea Profile (MDP) questionnaire and NT-proBNP level of <125 pg/mL for patients <75 years old or <300 pg/mL for patients >75 years old were recruited. Patients with known significant heart disease, lung disease (abnormal respiratory function tests) or renal insufficiency stage ≥ 4 were excluded. In 11 patients (16.7%), HFpEF was confirmed according to the European Society of Cardiology Heart Failure Association (ESC HFA) criteria, 31 patients (47%) presented isolated deconditioning and 5 patients (7.6%) had idiopathic hyperventilation. In the remaining 19 patients (28.8%) with normal echocardiography and cardiopulmonary exercise testing (CPX), no objective cause of dyspnoea could be found. Compared with patients without HFpEF, those with HFpEF were older, more often hypertensive and diabetic, with higher NT-proBNP levels. They had higher E/e' ratios during exercise echocardiography and lower volume of oxygen uptake (VO2) peaks and steeper minute ventilation (VE)/volume of carbon dioxide produced (VCO2) slopes during CPX. Psychological impact measured on the Short Form-36 (SF-36) questionnaire was less important in HFpEF patients than in other patients.

The most common causes of unexplained exertional dyspnoea in patients without significant elevation of natriuretic peptides are peripheral deconditioning, HFpEF and hyperventilation. Studying patients during exercise allows for getting more data about pathophysiology and improving patient phenotyping and management. Early unmasking of HFpEF using exercise echocardiography and/or CPX and initiation of treatment could prevent hospitalizations for acute heart failure. Although using exercise testing, many patients could not be classified according to their diagnosis, and this reinforces the need to better define exercise diagnostic criteria.

Heart failure (HF) is a significant global health issue, categorized by left ventricular ejection fraction, being either reduced (HFrEF < 0.40) or preserved (HFpEF > 0.50), or in the middle of this range. Although the overall incidence of HF remains stable, HFpEF cases are increasing, representing about 50% of all HF cases. Outcomes for HFpEF are similar to those for HFrEF, leading to substantial health-care resource use. Despite extensive research over the past 2 decades, the prognosis and mortality rates for HFpEF remain high. A key feature of HFpEF is exercise intolerance, characterized by severe exertional dyspnea and fatigue, which significantly impacts quality of life. The underlying mechanisms of exercise intolerance are not fully understood due to the complex pathophysiology and multisystem involvement. Obesity is a common comorbidity in HFpEF, especially in North America, leading to worsening symptoms, hemodynamics, and mortality rates. Increased adiposity leads to inflammation, hypertension, dyslipidemia, and insulin resistance, and impairing cardiac, vascular, pulmonary, and skeletal muscle function. Therefore, managing obesity is crucial in treating HFpEF. In this review we explore the pathophysiologic mechanisms of HFpEF, emphasizing obesity's role, and we discuss current management strategies while identifying areas needing further research.

Heart failure with preserved ejection fraction (HFpEF) is an ongoing challenge for healthcare systems. Major limitations that hinder adequate control of the disease, including an incomplete understanding of its pathophysiology, limited therapy options, and the absence of sufficient information on the management of comorbidities. Diagnosis and management of HFpEF in Egypt lack standardization as they are complicated with multiple comorbidities and limited by the lack of resources and data on epidemiology and patient characteristics. Diagnostic procedures for HFpEF should be implemented through guideline-specified scoring systems, due to the heterogeneity of clinical presentations and the absence of a golden standard for confirming HFpEF. In Egypt, the H2FPEF scoring system is more commonly used for establishing HFpEF diagnosis. All HFpEF patients should be treated through multidrug regimens tailored for their state, symptoms, and comorbidities, with sodium-glucose cotransporter-2 (SGLT2) inhibitors as the mainstay of treatment together with either one or a combination of loop diuretic and aldosterone antagonists. This paper provides an integrated review of epidemiology, means of diagnosis, current and novel pharmacological therapy options for HFpEF patients in the light of the recent advances in treatment of HFpEF, discussing means of healthcare delivery and unmet needs, and proposing recommendations for clinical practice and pathways for future research.

Exercise transthoracic Doppler echocardiography (TTE) is considered suggestive of left ventricular (LV) diastolic dysfunction when the ratio of mitral Doppler E to tissue Doppler e' waves is >15 with or without a peak tricuspid regurgitation velocity (TRV) >3.4 m/s. However, these measurements may be affected by exercise intensity. The aim of the study was to define the normal limits of LV diastolic function indices during exercise TTE.

One hundred ninety-two healthy adults (47% females, aged 16-76 years) underwent resting and exercise TTE on a semirecumbent cycle ergometer. LV diastolic measurements were acquired at baseline and midlevel exercise (heart rate ≤110 bpm) fusion of E and A waves. TRV was acquired at rest and at peak exercise. The E/e' ratio was calculated with e' as the average of septal and lateral measurements.

At midlevel exercise, E/e' increased modestly from 6.3 ± 1.9 to 7.3 ± 2.3 (P < 0.001) as a function of workload and cardiac output (CO), independently of sex and age. The 95th percentile of exercise E/e' was 11.8. The slope of E/e'/CO was 0.4 ± 1.2/L/min. The slope of TRV/CO was 10.8 ± 11.5 cm/s/L/min. The upper 95% confidence interval of the E/e'/CO and TRV/CO slopes were 0.6/L/min and 13.1 cm/s/L/min, corresponding to an E/e' of 13.2 and a TRV of 3.4 m/s at a CO of 15 L/min.

In healthy adult subjects, E/e' slightly increased during midlevel exercise. Both E/e' and TRV are exercise intensity-dependent and would therefore be better expressed as a function of CO for the diagnosis of normal vs abnormal LV diastolic response to exercise.

Heart failure with preserved ejection fraction (HFpEF) is a major healthcare problem with increasing prevalence. There has been a shift in HFpEF management towards early diagnosis and phenotype-specific targeted treatment. However, diagnosing HFpEF remains challenging due to a lack of universal criteria and patient heterogeneity. This review aims to provide a comprehensive assessment of the diagnostic workup of HFpEF, highlighting the role of echocardiography in HFpEF phenotyping.

The rising prevalence of obesity and its association with heart failure with preserved ejection fraction (HFpEF) highlight an urgent need for a diagnostic approach tailored to this population. Diagnosing HFpEF is hampered by the lack of a single non-invasive diagnostic criterion. While this makes a firm diagnosis of HFpEF already notoriously difficult in the general population, it is even more challenging in individuals with obesity. The challenges stem from a range of factors, including the use of body mass index as a conceptually suboptimal indicator of health risks associated with increased body mass, symptom overlap between HFpEF and obesity, limitations in physical examination, difficulties in electrocardiographic and echocardiographic evaluation, and reduced diagnostic sensitivity of natriuretic peptides in individuals with obesity. In this review, we examine these diagnostic challenges and propose a diagnostic algorithm specifically tailored to improve the accuracy and reliability of HFpEF diagnosis in this growing patient demographic.

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.

Heart failure and cancer remain 2 of the leading causes of morbidity and mortality, and the 2 disease entities are linked in a complex manner. Patients with cancer are at increased risk of cardiovascular complications related to the cancer therapies. The presence of cardiomyopathy or heart failure in a patient with new cancer diagnosis portends a high risk for adverse oncology and cardiovascular outcomes. With the rapid growth of cancer therapies, many of which interfere with cardiovascular homeostasis, heart failure practitioners need to be familiar with prevention, risk stratification, diagnosis, and management strategies in cardio-oncology. This Heart Failure Society of America statement addresses the complexities of heart failure care among patients with active cancer diagnoses and cancer survivors. Risk stratification, monitoring and management of cardiotoxicity are presented across stages A through D heart failure, with focused discussion on heart failure with preserved ejection fraction and special populations, such as survivors of childhood and young-adulthood cancers. We provide an overview of the shared risk factors between cancer and heart failure, highlighting heart failure as a form of cardiotoxicity associated with many different cancer therapeutics. Finally, we discuss disparities in the care of patients with cancer and cardiac disease and present a framework for a multidisciplinary-team approach and critical collaboration among heart failure, oncology, palliative care, pharmacy, and nursing teams in the management of these complex patients.

Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are increasingly prevalent cardiovascular conditions, particularly among the elderly population. These two conditions share common risk factors and often coexist, leading to a complex interplay that alters the clinical course of each other. The pathophysiology of HFpEF is multifaceted and intricately linked, with atrial disease serving as a common pathophysiological pathway. Diagnosis of HFpEF in the setting of AF, and vice versa, can be challenging; thus, effective screening and diagnostic strategies are needed. Understanding the complex relationship between HFpEF and AF is crucial for optimal patient management by timely disease recognition and identification of therapeutic interventions or treatment strategies.

Insulin resistance (IR) plays a pivotal role in the interplay between metabolic disorders and heart failure with preserved ejection fraction (HFpEF). Various non-insulin-based indices emerge as reliable surrogate markers for assessing IR, including the triglyceride-glucose (TyG) index, the TyG index with body mass index (TyG-BMI), atherogenic index of plasma (AIP), and the metabolic score for insulin resistance (METS-IR). However, the ability of different IR indices to predict outcome in HFpEF patients has not been extensively explored.

Patients having HFpEF were recruited from January 2012 and December 2023. The outcome was defined as major adverse cardiovascular event (MACE), encompassing all-cause mortality and rehospitalization for heart failure. The potential linear relationship was visualized by the restricted cubic spline (RCS) curve. Both univariable and multivariable Cox proportional hazards models were employed to examine the association between the IR indexes and MACE. Furthermore, to assess the incremental prognostic value of the TyG index, we conducted comprehensive analyses using area under the curve (AUC), the continuous net reclassification index (cNRI), and the integrated discrimination index (IDI).

A total of 8693 patients met the inclusion criteria and were included in the final analysis. The mean age of the patients was 70.59 ± 10.6 years, with 5045 (58.04%) being male. The Kaplan-Meier survival analysis revealed that higher degree of the four IR indexes was associated with higher risk of MACE (all log-rank P < 0.05). When treated as a continuous variable, the TyG index showed a significant association with MACE (HR 2.1, 95% CI 1.98-2.23, P < 0.001 in model 1; HR 1.81, 95% CI 1.73-1.9, P < 0.001 in model 2; HR 1.68, 95% CI 1.6-1.76, P < 0.001 in model 3). When categorized into quartiles, the highest quartile of the TyG index (Q4) was significantly associated with MACE (HR 2.48, 95% CI 2.24-2.76, P < 0.001 in model 3). Similar significant associations were found between TyG-BMI, AIP, METS-IR, and MACE. The TyG index was found to enhance the risk stratification capability of the MAGGIC score (AUC from 0.601 to 0.666). When compared to other IR indicators, the TyG index exhibited superior discrimination and reclassification abilities in predicting MACE. Additionally, the TyG-BMI index revealed a U-shaped correlation with MACE, indicating that both an elevated and a lower TyG-BMI index were associated with an increased risk.

All four IR indices are independently associated with MACE in patients with HFpEF. Notably, these IR indices significantly enhance the predictive accuracy of the MAGGIC score, a widely used risk assessment tool in HFpEF. Among these indices, the TyG index demonstrated the highest discriminatory and reclassification abilities, providing the greatest incremental value in predicting MACE and exhibiting significant superiority compared to the other indices. These findings highlight the importance of assessing IR indices, particularly the TyG index, in the risk assessment and management strategies for HFpEF patients. However, it should be noted that our findings need to be validated in diverse populations to ensure their applicability and generalizability.

The initiation of sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment was shown to reduce pulmonary artery pressure (PAP) in New York Heart Association (NYHA) class III heart failure (HF) patients with an implanted PAP sensor. We aimed to investigate the impact of SGLT2-I initiation on pulmonary vascular resistance (PVR), pulmonary capillary wedge pressure (PCWP), pulmonary arterial capacitance (PAC), and right ventricle (RV) to PA (RV-PA) coupling in a pilot cohort of HF with preserved/mildly reduced ejection fraction (HFpEF/HFmrEF) patients and whether PVR and PCWP can be serially calculated non-invasively using PAP sensor data during follow-up.

Right heart catheterization parameters (PVR, PCWP, and PAC) were obtained at sensor implantation and echocardiographic assessments (E/E', RV-PA coupling, and RV cardiac output) were made at baseline and every 3 months. SGLT2 inhibition was initiated after 3 months of telemedical care. Three methods for calculating PVR and PCWP were compared using Bland-Altman plots and Spearman's correlation.

In 13 HF patients (mean age 77 ± 4 years), there were no significant changes in PAP, PVR, PCWP, RV-PA coupling, or PAC over 9 months (all p-values > 0.05), including after SGLT2-I initiation. PVR values were closely correlated across the three methods (PVRNew and PVRNew Tedford (r = 0.614, p < 0.001), PVREcho and PVRNew Tedford (r = 0.446, p = 0.006), and PVREcho and PVRNew (r = 0.394, p = 0.016)), but PCWP methods lacked reliable association (PCWPEcho and PCWPNew (r = 0.180, p = 0.332).

No changes in cardiopulmonary hemodynamics were detected after hemodynamic telemonitoring either prior to or following SGLT2-I initiation. Different PVR assessment methods yielded comparable results, whereas PCWP methods were not associated with each other. Further investigations with larger cohorts including repeated right heart catheterization are planned.

Despite increasing awareness in general practice, heart failure with preserved ejection fraction (HFpEF) remains under-diagnosed in the community due to diagnostic difficulties. Dedicated dyspnea clinics are responsible for diagnosing HFpEF and efficient referral from primary care physicians is the key to enhance its role.

This retrospective analysis was performed to assess the effectiveness of a one-year collaborative project between our dyspnea clinic and the Maebashi Medical Association. Primary care physicians were encouraged to screen patients at risk for HFpEF and refer them to the dyspnea clinic, where exercise stress echocardiography was utilized to enhance the identification of HFpEF. To evaluate the clinical value of the project, the data obtained were compared with data from the previous year without collaboration.

The collaborative project was conducted between May 2023 and May 2024. The rate of patients referred from the city increased from 47 % during the previous year to 87 % during the collaborative period (p < 0.0001). Most of the patients were referred by non-cardiologists (77 %). The prevalence of HFpEF diagnosis tended to increase from 32 % to 39 % after the collaborative project, while pulmonary causes of dyspnea tended to decrease from 21 % to 12 %. After a thorough evaluation at the dyspnea clinic, 98 % of referred patients were referred back to their referring physicians for further treatment and follow-up.

These data suggest the effectiveness of our approach to identify HFpEF in the community through collaboration between the dedicated dyspnea clinic and primary care physicians.

Evaluation of pulmonary capillary wedge pressure (PCWP) through right heart catheterization can indirectly provide an estimation of the filling pressure of the left ventricle. Echocardiography can estimate left ventricular compliance using mitral annular tissue Doppler imaging (TDI). The E/e' ratio refers to the correlation between the peak mitral inflow (E-wave) velocity and early diastolic tissue Doppler mitral annular velocity (e'). The main purpose of this systematic review was to establish the correlation between echocardiographic E/e' ratio and PCWP. The correlation between E/e' and left ventricular end-diastolic pressure (LVEDP) was evaluated as a secondary objective.

A systematic review and meta-analysis of observational studies was conducted. The search was based on Medline (PubMed), Scopus, and Web of Science.

Intensive care unit or cardiac intensive care unit.

Adult patients.

Any study comparing the left ventricular filling pressure obtained by cardiac catheterization (reference) and echocardiographic evaluation, in particular TDI analysis (intervention), were included.

The pooled analysis included 94 studies from the initially identified 7,304 records. The correlation was 0.48 (95% CI 0.42-0.54, Q = 420.52, I2 = 84.8%) for PCWP and 0.50 (95% CI 0.38-0.60, Q = 210.91, I2 = 89.1%) for LVEDP.

The E/e' ratio moderately correlated with PCWP/LVEDP. The correlation was stable irrespective of the sites where e' was measured, but each site has its own limitations for specific patient subpopulations. The correlation was weak in patients with heart failure with a preserved ejection fraction.

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.

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.

Cardiopulmonary exercise testing (CPET) combined with exercise echocardiography (CPETecho) allows simultaneous assessments of cardiac, pulmonary, and ventilation in heart failure (HF) with preserved ejection fraction (HFpEF). This study sought to determine whether simultaneous assessment of CPET variables could provide additive predictive value over exercise stress echocardiography in patients with dyspnoea.

CPETecho was performed in 443 patients with suspected HFpEF (240 HFpEF and 203 controls without HF). Patients with HFpEF were divided based on peak oxygen consumption (VO2, ≥10 or <10 ml/min/kg) or the slope of minute ventilation to carbon dioxide production (VE vs. VCO2 slope ≥45.0 or <45.0). The primary endpoint was defined as a composite of all-cause mortality, HF hospitalization, unplanned hospital visits requiring intravenous diuretics, or intensification of oral diuretics. During a median follow-up of 399 days, the composite outcome occurred in 57 patients. E/e' ratio during peak exercise was associated with adverse outcomes. Patients with HFpEF and lower peak VO2 had increased risks of the composite event (hazard ratio [HR] 5.05, 95% confidence interval [CI] 2.65-9.62, p < 0.0001 vs. controls; HR 3.14, 95% CI 1.69-5.84, p = 0.0003 vs. HFpEF with higher peak VO2). Elevated VE versus VCO2 slope was also associated with adverse events in HFpEF. The addition of either the presence of abnormal peak VO2 or VE versus VCO2 slope increased the predictive ability over the model based on age, sex, atrial fibrillation, left atrial volume index, and exercise E/e' (p < 0.05).

These data provide new insights into the role of CPETecho in patients with HFpEF.

In the absence of left-sided cardiac/pulmonary disease, functional tricuspid regurgitation (FTR) is referred to as isolated or idiopathic. Relationships between left ventricular diastolic dysfunction (DD) and FTR remain unknown.

The purpose of this study was to investigate the prevalence, incidence, and outcome of DD in patients with idiopathic FTR.

Adults without structural heart disease were identified. Severe DD was defined by ≥3 of 4 abnormal DD parameters (medial e', medial E/e', TR velocity, left atrial volume index) and ≥ moderate DD by ≥2. Propensity-score matching was performed (3:1) between each less-than-severe TR group and severe TR based on age, sex, body mass index, and comorbidities.

Among 30,428 patients, FTR was absent in 73%, mild in 22%, moderate in 4%, and severe in 0.4%. In the propensity-matched sample, severe DD was present in 2%, 6%, 9%, and 13% patients, and ≥ moderate DD in 11%, 18%, 28%, and 48%, respectively (P < 0.001). The probability of heart failure with preserved ejection fraction using the H2FPEF score increased with increasing FTR (median 29.7%, 45.5%, 61.4%, and 88.7%, respectively), as did the prevalence of impaired left atrial strain <24% (35%, 48%, and 69% in mild, moderate, and severe TR). Incident severe and ≥ moderate DD developed more frequently with increasing FTR (HR: 8.45 [95% CI: 2.60-27.50] and HR: 2.82 [95% CI: 1.40-5.69], respectively for ≥ moderate vs no FTR) over a median of 3.0 years. Findings were confirmed in patients without lung disease or right ventricular enlargement. Over a median of 5.0 years, patients with ≥ moderate FTR and DD had the greatest risk of worse outcomes (multivariable P < 0.001). The association between TR and adverse outcomes was significantly diminished in the absence of DD.

Diastolic dysfunction, increased heart failure with preserved ejection fraction probability, and impaired left atrial strain are commonly present in patients with idiopathic FTR, suggesting that the latter may not be truly isolated. Patients with FTR without DD or heart failure are at increased risk of incident DD. Patients with FTR and DD display worse outcomes.

Exercise-induced pulmonary hypertension (exPHT) is a haemodynamic condition linked to increased morbidity and mortality across various cardiopulmonary diseases. Traditional definitions of exPHT rely on absolute cut-offs, such as mean pulmonary artery pressure (mPAP) above 30 mmHg during exercise. However, recent research suggests that these cut-offs may not accurately reflect pathophysiological changes, leading to false positives and false negatives. Instead, the mPAP over cardiac output (CO) slope, which incorporates both pressure and flow measurements, has emerged as a more reliable indicator. A slope exceeding 3 mmHg/L/min is now considered diagnostic for exPHT and strongly correlates with adverse outcomes. Stress echocardiography serves as a viable alternative to invasive assessment, enabling broader implementation. This review discusses the physiological basis of pulmonary haemodynamics during exercise, the advantages of the mPAP/CO slope over absolute pressure measurements, the evidence supporting its inclusion in clinical guidelines, and provides a practical guide for non-invasive determining the mPAP/CO slope in clinical practice.

Background and Objectives: Heart failure (HF) is one of the most common initial presentations of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). There are different cardiac biomarkers related to the pathophysiological mechanisms of HF in T2DM. The current research aims to identify additional biomarkers that could improve the diagnosis and prognosis of HFpEF, which is currently assessed using NT pro-BNP levels. NT pro-BNP is a valuable tool for diagnosing heart failure but may not always correlate with clinical symptom severity or can present normal levels in certain cases, such as obesity. Biomarkers like FGF-21 and galectin-3 could provide greater insight into heart failure severity, especially in diabetic patients. The main objective of the current study is to assess the performance of NT-proBNP, FGF21, Galectin-3 and Copeptin to discriminate between advanced and mild HF. Materials and Methods: A total of 117 patients were enrolled in this study and divided into two groups: 67 patients in NYHA functional class I-II (mild HF) and 50 patients in NYHA III-IV (advanced HF). NT-pro BNP, FGF21, Galectin 3 and Copeptin serum levels were determined with the ELISA method. Receiver operating characteristic (ROC) analysis and binomial logistic regression analysis were used to measure the ability of the studied biomarkers to distinguish between advanced and mild HF patients. Results: In patients with T2DM with advanced HF, serum FGF21 level was significantly positively correlated with eGFR (ρ = 0.35, p = 0.0125) and triglycerides (ρ = 0.28, p = 0.0465) and significantly negatively correlated with serum levels of HDL cholesterol (ρ = -0.29, p = 0.0386) and with RV-RA gradient (ρ = -0.30, p = 0.0358). In patients with mild HF, serum FGF21 level was significantly negatively correlated with NT-proBNP levels (ρ = -0.37, p = 0.0022), E/e' ratio (ρ = -0.29, p = 0.0182), TR velocity (ρ = -0.24, p = 0.0470) and RV-RA gradient (ρ = -0.24, p = 0.0472). FGF21 (AUC = 0.70, 95% CI: 0.60-0.79) and NT-proBNP (AUC = 0.73, 95% CI: 0.63-0.82) demonstrated significant predictive value to discriminate T2DM patients with advanced HF from those with mild HF. Elevated values for FGF21 (≥377.50 ng/mL) or NTproBNP (≥2379 pg/mL) were significantly associated with increased odds of advanced HF after adjusting for demographic and clinical covariates. Conclusions: NTpro-BNP and FGF21 have a similar ability to discriminate T2DM patients with advanced HF from those with mild HF. Univariable and multivariable logistic models showed that, FGF21 and NTproBNP were independent predictors for advanced HF in patients with preserved and mildly reduced ejection fraction and T2DM.

Heart failure with preserved ejection fraction (HFpEF) is associated with high hospitalization and mortality rates, representing a significant healthcare burden. This study aims to utilize various information including echocardiogram and phonocardiogram to construct and validate a nomogram, assisting in clinical decision-making.

This study analyzed 204 patients (68 HFpEF and 136 non-HFpEF) from the First Affiliated Hospital of Chongqing Medical University. A total of 49 features were integrated and used, including phonocardiogram, echocardiogram features, and clinical parameters. The least absolute shrinkage and selection operator (LASSO) regression was used to select the optimal matching factors, and a stepwise logistic regression was employed to determine independent risk factors and develop a nomogram. Model performance was evaluated by the area under receiver operating characteristic (ROC) curve (AUC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC).

The nomogram was constructed using five significant indicators, including NT-proBNP (OR = 4.689, p = 0.015), E/e' (OR = 1.219, p = 0.032), LAVI (OR = 1.088, p < 0.01), D/S (OR = 0.014, p < 0.01), and QM1 (OR = 1.058, p < 0.01), and showed a better AUC of 0.945 (95% CI = 0.908-0.982) in the training set and 0.933 (95% CI = 0.873-0.992) in the testing set compared to conventional nomogram without phonocardiogram features. The calibration curve and Hosmer-Lemeshow test demonstrated no statistical significance in the training and testing sets (p = 0.814 and p = 0.736), indicating the nomogram was well-calibrated. The DCA and CIC results confirmed favorable clinical usefulness.

The nomogram, integrating phonocardiogram and echocardiogram features, enhances HFpEF diagnostic efficiency, offering a valuable tool for clinical decision-making.

Despite remarkable progress in therapeutic drugs, morbidity, and mortality for heart failure (HF) remains high in developed countries. HF with preserved ejection fraction (HFpEF) now accounts for around half of all HF cases. It is a heterogeneous disease, with multiple aetiologies, and as such poses a significant diagnostic challenge. Cardiac magnetic resonance (CMR) has become a valuable non-invasive modality to assess cardiac morphology and function, but beyond that, the multi-parametric nature of CMR allows novel approaches to characterize haemodynamics and with magnetic resonance spectroscopy (MRS), the study of metabolism. Furthermore, exercise CMR, when combined with lung water imaging provides an in-depth understanding of the underlying pathophysiological and mechanistic processes in HFpEF. Thus, CMR provides a comprehensive phenotyping tool for HFpEF, which points towards a targeted and personalized therapy with improved diagnostics and prevention.

Heart failure with preserved ejection fraction (HFpEF) is a major healthcare problem that is raising in prevalence. There has been a shift in HpEF management towards early diagnosis and phenotype-specific targeted treatment. However, the diagnosis of HFpEF remains a challenge due to the lack of universal criteria and patient heterogeneity. This review aims to provide a comprehensive assessment of the diagnostic workup of HFpEF, highlighting the role of echocardiography in HFpEF phenotyping.

Evidence for risk stratification using exercise stress echocardiography (ESE) in patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) is currently lacking. Cardiac power output (CPO) has demonstrated prognostic value in patients undergoing TAVI for severe AS. This study investigated prognoses in patients undergoing TAVI for severe AS and to explore the additional information that ESE can provide for risk stratification.

In this retrospective observational study, we included 96 consecutive patients who underwent TAVI for severe AS and patients with preserved left ventricular (LV) ejection fraction (≥ 50%) who underwent ESE at 3-6 months after TAVI. CPO was calculated as 0.222 × cardiac output × mean blood pressure/LV mass, where 0.222 was the conversion constant to W/100 g of the LV myocardium. All patients were followed up for all-cause mortality and hospitalization for heart failure.

Of the 96 patients, 3 were excluded and 93 patients (82.0 years; 45.2% male) were included in this study. During a median follow-up period of 1446 (1271-1825) days, the composite end point was reached in 17 patients. Multivariable Cox regression analysis revealed that CPO at rest and the change in CPO from rest to exercise (ΔCPO) were independently associated with the composite end point (hazard ratio = 0.278, p = 0.023). The addition of ΔCPO resulted in an incremental value of the model containing clinical and resting echocardiography variables (p = 0.030).

This study suggests that resting CPO and exercise-induced changes in CPO are useful for risk stratification of patients undergoing TAVI for severe AS.

The H2FPEF and the HFA-PEFF scores have become useful tools to diagnose heart failure with preserved ejection fraction (HFpEF). Their accuracy in patients with a history of atrial fibrillation (AF) is less known. This study evaluates the association of these scores with invasive left atrial pressure (LAP) and the additional value of cardiac measures.

This is a multicenter observational prospective study involving patients undergoing ablation of AF. Patients with left ventricular ejection fraction (LVEF) < 40%, congenital cardiopathy, any severe cardiac valve disease and prosthetic valves were excluded. Elevated filling pressure was defined as a mean LAP ≥15 mmHg.

A total of 135 patients were enrolled in the study (mean age 65.2 ± 9.1 years, 32% female, mean LVEF 56.9 ± 7.9%). Patients with H2FPEF ≥ 6 or HFA-PEFF ≥5 had higher values of NTproBNP and more impaired cardiac function. However, neither H2FPEF nor HFA-PEFF score showed a meaningful association with elevated mean LAP (respectively, OR 1.05 [95%CI 0.83-1.34] p = 0.64, and OR 1.09 [95%CI: 0.86-1.39] p = 0.45). The addition of LA indexed minimal volume (LAVi min) improved the ability of the scores (baseline C-statistic 0.51 [95%CI 0.41-0.61] for the H2FPEF score and 0.53 [95%CI 0.43-0.64] for the HFA-PEFF score) to diagnose elevated filling pressure (H2FPEF + LAVi min: C-statistic 0.70 [95%CI 0.60-0.80], p-value = 0.005; HFA-PEFF + LAVi min: C-statistic 0.70 [95%CI 0.60-0.80], p-value = 0.02).

In a cohort of patients with a history of AF, the use of the available diagnostic scores did not predict elevated mean LAP. The integration of LAVi min improved the ability to correctly identify elevated filling pressure.

To review the most recent clinical trials and data regarding epidemiology, pathophysiology, diagnosis, and treatment of heart failure with preserved ejection fraction with an emphasis on the recent trends in cardiometabolic interventions.

Heart failure with preserved ejection fraction makes up approximately half of overall heart failure and is associated with significant morbidity, mortality, and overall burden on the healthcare system. It is a complex, heterogenous syndrome and clinical trials, to this point, have not revealed quite as many effective treatment options when compared to heart failure with reduced ejection fraction. Nevertheless, there is an expanding amount of data insight into the pathogenesis of this disease and the potential for newer therapies and management strategies. Heart failure with preserved ejection fraction pathology has been found to be linked to abnormal energetics, myocyte hypertrophy, cell signaling, inflammation, ischemia, and fibrosis. These mechanisms also intricately overlap with the significant comorbidities often associated with heart failure with preserved ejection fraction including, but not limited to, atrial fibrillation, chronic kidney disease, hypertension, obesity and coronary artery disease. Treatment of this disease, therefore, should focus on the management and strict regulation of these comorbidities by pharmacologic and nonpharmacologic means. In this review, a clinical update is provided reviewing the most recent clinical trials and data regarding epidemiology, pathophysiology, diagnosis, and treatment of heart failure with preserved ejection fraction with an emphasis on the recent trend in cardiometabolic interventions.

Systemic arterial compliance and venous capacitance are typically impaired in patients with heart failure with preserved ejection fraction (HFpEF), contributing to hemodynamic congestion with stress. Sodium-glucose cotransporter-2 inhibitors reduce hemodynamic congestion and improve clinical outcomes in patients with HFpEF, but the mechanisms remain unclear. This study tested the hypothesis that Dapagliflozin would improve systemic arterial compliance and venous capacitance during exercise in patients with HFpEF.

In this secondary analysis from the CAMEO-DAPA trial (Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction Trial), 37 patients with HFpEF (mean age 68 ± 9 years, women 65%) underwent invasive hemodynamic exercise testing with simultaneous echocardiography at baseline and following treatment for 24 weeks with Dapagliflozin or placebo. Radial artery pressure (BP) was measured continuously using a fluid-filled catheter with transformation to aortic pressure, central hemodynamics were measured using high-fidelity micromanometers, and stressed blood volume was estimated from hemodynamic indices fit to a comprehensive cardiovascular model.

There was no statistically significant effect of Dapagliflozin on resting BP, but Dapagliflozin reduced systolic BP during peak exercise (estimated treatment difference [ETD], -18.8 mm Hg [95% CI, -33.9 to -3.7] P=0.016). Reduction in BP was related to improved exertional total arterial compliance (ETD, 0.06 mL/mm Hg/m2 [95% CI, 0.003-0.11] P=0.039) and aortic root characteristic impedance (ETD, -2.6 mm Hg/mL*sec [95% CI: -5.1 to -0.03] P=0.048), with no significant effect on systemic vascular resistance. Dapagliflozin reduced estimated stressed blood volume at rest and during peak exercise (ETD, -292 mm Hg [95% CI, -530 to -53] P=0.018), and improved venous capacitance evidenced by a decline in ratio of estimated stressed blood volume to total blood volume (ETD, -7.3% [95% CI, -13.3 to -1.3] P=0.020). Each of these effects of Dapagliflozin at peak exercise were also observed during matched 20W exercise intensity. Improvements in total arterial compliance and estimated stressed blood volume were correlated with decreases in body weight, and reduction in systolic BP with treatment was correlated with the change in estimated stressed blood volume during exercise (r=0.40, P=0.019). Decreases in BP were correlated with reduction in pulmonary capillary wedge pressure during exercise (r=0.56, P<0.001).

In patients with HFpEF, treatment with Dapagliflozin improved systemic arterial compliance and venous capacitance during exercise, while reducing aortic characteristic impedance, suggesting a reduction in arterial wall stiffness. These vascular effects may partially explain the clinical benefits with sodium-glucose cotransporter-2 inhibitors in HFpEF.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT04730947.

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.