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Heart failure with preserved ejection fraction (HFpEF) represents one of the greatest unmet needs in modern cardiology given its diagnostic difficulty and limited therapeutic options. Echocardiography provides valuable information on cardiac structure, function, and hemodynamics and plays a central role in the evaluation of HFpEF. Echocardiography is crucial in identifying HFpEF among patients with dyspnea, especially when overt congestion is absent. The combination of echocardiographic indices of diastolic function, clinical characteristics, and natriuretic peptide tests has been proposed in the diagnostic evaluation of patients with suspected HFpEF. Echocardiography also provides valuable insight into the pathophysiology and underlying phenotypes of HFpEF. Exercise stress echocardiography can also detect abnormalities that develop only during exercise. This may enhance the diagnosis of HFpEF by demonstrating elevation in the left ventricular filling pressure and may have potential for better pathophysiological characterization. This review focuses on the role of echocardiography in the diagnostic evaluation and phenotyping of HFpEF. We also discuss the potential role of exercise stress echocardiography for the diagnosis and disease phenotyping of HFpEF.

Heart Failure with preserved Ejection Fraction (HFpEF) is nowadays considered a major healthcare issue. According to forecasts two third of all Heart Failure patients will belong to this phenotype by year 2050, overwhelming those affected by Heart Failure with reduced Ejection Fraction (HFrEF). Both epidemiological and mechanistic studies support the concept that HFpEF represents true HF although aggravated by a collection of comorbidities. There is urgent need of improving its phenotyping due to the high degree of disease heterogeneity within HFpEF that lead to the failure of randomized clinical trials in demonstrating a remarkable impact of drugs in improving its morbidity and mortality.

Pulmonary hypertension (PH) often complicates chronic left-sided heart failure, with a remarkable impact on quality of life, exercise capacity, and survival. PH in chronic left-sided heart failure (PH-LHD) is not only caused by backward transmission of pressures but also involves impairment of atrial function, inflammation, and vasoconstriction. Once the left atrium loses its reservoir capacity, usually pulmonary vascular resistances increase. Right atrial dilation commonly represents the first sign of PH-LHD, before right ventricle dilatation and systolic dysfunction develop, leading to right heart insufficiency, and ultimately, right heart failure.

Background : Heart failure with preserved ejection fraction (HFpEF) is the fastest growing form of HF and is associated with high morbidity and mortality. The primary chronic symptom in HFpEF is exercise intolerance, associated with reduced quality of life (QoL). Emerging evidence implicates left atrial (LA) dysfunction as an important pathophysiologic mechanism. Here we extend prior observations by relating LA dysfunction to peak oxygen uptake (peak VO2), physical function (distance walked in six minutes, 6MWD) and QoL (Kansas City Cardiomyopathy Questionnaire, KCCQ). Methods : We compared 75 older, obese, HFpEF patients to 53 healthy age-matched controls. LA strain was assessed by magnetic resonance cine imaging using feature tracking. LA function was defined according to its three distinct phases, with the LA serving as a reservoir during systole, as a conduit during early diastole, and as a booster pump at the end of diastole. LA stiffness index was calculated as the ratio of early mitral inflow velocity-to-early annular tissue velocity (E/e’, by Doppler ultrasound) and LA reservoir strain. Results : HFpEF had decreased reservoir strain (16.4±4.4% vs. 18.2±3.5%, p=0.018), lower conduit strain (7.7±3.3% vs. 9.1±3.4%, p=0.028), and increased stiffness index (0.86±0.39 vs. 0.53±0.18, p Conclusion : LA stiffness is independently associated with impaired exercise tolerance and QoL and may be an important therapeutic target in obese HFpEF. Registration : NCT00959660

The authors hypothesized that quantitative computed tomography (QCT) imaging would reveal subclinical increases in lung congestion in patients with heart failure and preserved ejection fraction (HFpEF) and that this would be related to pulmonary vascular hemodynamic abnormalities.Gross evidence of lung congestion on physical examination, laboratory tests, and radiography is typically absent among compensated ambulatory patients with HFpEF. However, pulmonary gas transfer abnormalities are commonly observed and associated with poor outcomes.Patients referred for invasive hemodynamic exercise testing who had undergone chest computed tomography imaging within 1 month were identified (N = 137). A novel artificial intelligence QCT algorithm was used to measure pulmonary fluid content.Compared with control subjects with noncardiac dyspnea, patients with HFpEF displayed increased mean lung density (-758 HU [-793, -709 HU] vs -787 HU [-828, -747 HU]; P = 0.002) and a higher ratio of extravascular lung water to total lung volume (EVLWV/TLV) (1.25 [0.80, 1.76] vs 0.66 [0.01, 1.03]; P 0.0001) by QCT imaging, indicating greater lung congestion. EVLWV/TLV was directly correlated with pulmonary vascular pressures at rest, with stronger correlations observed during exercise. Patients with increasing tertiles of EVLWV/TLV demonstrated higher mean pulmonary artery pressures at rest (34 ± 11 mm Hg vs 39 ± 14 mm Hg vs 45 ± 17 mm Hg; P = 0.0003) and during exercise (55 ± 17 mm Hg vs 59 ± 17 mm Hg vs 69 ± 22 mm Hg; P = 0.0003).QCT imaging identifies subclinical lung congestion in HFpEF that is not clinically apparent but is related to abnormalities in pulmonary vascular hemodynamics. These data provide new insight into the long-term effects of altered hemodynamics on pulmonary structure and function in HFpEF.

Objectives The authors sought to elucidate the prognostic value of cardiac sympathetic nerve dysfunction as evaluated using iodine-123-labeled metaiodobenzylguanidine (123I-MIBG) single-ph...

BACKGROUND Galectin-1 is a glycan-binding protein with broad anti-inflammatory properties. Left ventricular diastolic dysfunction (DD) is associated with heart failure and mortality. The pathophysiology of DD is complex and our study aimed to investigate the associations between serum galectin-1 level, DD, and heart failure with preserved ejection fraction (HFpEF). METHODS Patients with symptoms of angina pectoris were enrolled. Serum galectin-1 levels and echocardiography were assessed. The study endpoint was a composite of all-cause mortality or new-onset HFpEF. RESULTS In total, 258 patients were enrolled (63% male; mean age 68±12 years) and grouped into tertiles based on galectin-1 levels. Patients in the highest galectin-1 group had increased left ventricular mass indexes, left atrial diameters, and prevalence of DD compared to those in the lower tertiles (all p

This Atlas chapter summarizes sex- and some gender-associated, and unique aspects and manifestations of cardiovascular disease (CVD) in women. CVD is the primary cause of premature death in women in Canada and numerous sex-specific differences related to symptoms and pathophysiology exist. A review of the literature was done to identify sex-specific differences in symptoms, pathophysiology, and unique manifestations of CVD in women. Although women with ischemic heart disease might present with chest pain, the description of symptoms, delay between symptom onset and seeking medical attention, and prodromal symptoms are often different in women, compared with men. Nonatherosclerotic causes of angina and myocardial infarction, such as spontaneous coronary artery dissection are predominantly identified in women. Obstructive and nonobstructive coronary artery disease, aortic aneurysmal disease, and peripheral artery disease have worse outcomes in women compared with men. Sex differences exist in valvular heart disease and cardiomyopathies. Heart failure with preserved ejection fraction is more often diagnosed in women, who experience better survival after a heart failure diagnosis. Stroke might occur across the lifespan in women, who are at higher risk of stroke-related disability and age-specific mortality. Sex- and gender-unique differences exist in symptoms and pathophysiology of CVD in women. These differences must be considered when evaluating CVD manifestations, because they affect management and prognosis of cardiovascular conditions in women.Dans le présent chapitre d’Atlas sont récapitulés les aspects et les manifestations uniques, associés au sexe et certains associés au genre, des maladies cardiovasculaires (MCV) chez les femmes. Les MCV sont la cause principale de décès prématurés chez les femmes au Canada. De nombreuses différences quant aux symptômes et à la physiopathologie existent entre les sexes. Nous avons réalisé une revue de la littérature pour déterminer les différences entre les sexes dans les symptômes et la physiopathologie, et les manifestations uniques des MCV chez les femmes. Bien que les femmes atteintes d’une cardiopathie ischémique puissent éprouver des douleurs thoraciques, la description des symptômes, le délai entre l’apparition des symptômes et l’obtention de soins médicaux, et les symptômes prodromiques sont souvent différents de ceux des hommes. Les causes de l’angine et de l’infarctus du myocarde non liées à l’athérosclérose telles que la dissection spontanée de l’artère coronaire sont principalement observées chez les femmes. La coronaropathie obstructive et non obstructive, l’anévrisme aortique et la maladie artérielle périphérique montrent de plus mauvaises issues chez les femmes que chez les hommes. Des différences entre les sexes sont observées dans la cardiopathie valvulaire et les cardiomyopathies. Le diagnostic d’insuffisance cardiaque avec fraction d’éjection préservée est plus souvent posé chez les femmes qui présentent un meilleur taux de survie après un diagnostic d’insuffisance cardiaque. L’accident vasculaire cérébral (AVC) pourrait survenir tout au long de la vie des femmes, qui sont exposées à un risque plus élevé d’incapacités liées à l’AVC et de mortalité par âge. Il existe des différences uniques entre les sexes et les genres pour ce qui est des symptômes et de la physiopathologie des MCV chez les femmes. Lors de l’évaluation des manifestations des MCV, il faut tenir compte de ces différences puisqu’elles influencent la prise en charge et le pronostic des maladies cardiovasculaires chez les femmes.

Background Despite exercise being one of few strategies to improve outcomes for individuals with heart failure with preserved ejection fraction (HFpEF), exercise clinical trials in HFpEF are plagued by poor interventional adherence. Over the last 2 decades, our research team has developed, tested, and refined Heart failure Exercise And Resistance Training (HEART) Camp, a multicomponent behavioral intervention to promote adherence to exercise in HF. We evaluated the effects of this intervention designed to promote adherence to exercise in HF focusing on subgroups of participants with HFpEF and heart failure with reduced ejection fraction (HFrEF). Methods and Results This randomized controlled trial included 204 adults with stable, chronic HF. Of those enrolled, 59 had HFpEF and 145 had HFrEF. We tested adherence to exercise (defined as ≥120 minutes of moderate-intensity [40%–80% of heart rate reserve] exercise per week validated with a heart rate monitor) at 6, 12, and 18 months. We also tested intervention effects on symptoms (Patient-Reported Outcomes Measurement Information System-29 and dyspnea-fatigue index), HF-related health status (Kansas City Cardiomyopathy Questionnaire), and physical function (6-minute walk test). Participants with HFpEF (n = 59) were a mean of 64.6 ± 9.3 years old, 54% male, and 46% non-White with a mean ejection fraction of 55 ± 6%. Participants with HFpEF in the HEART Camp intervention group had significantly greater adherence compared with enhanced usual care at both 12 (43% vs 14%, phi = 0.32, medium effect) and 18 months (56% vs 0%, phi = 0.67, large effect). HEART Camp significantly improved walking distance on the 6-minute walk test (η2 = 0.13, large effect) and the Kansas City Cardiomyopathy Questionnaire overall (η2 = 0.09, medium effect), clinical summary (η2 = 0.16, large effect), and total symptom (η2 = 0.14, large effect) scores. In the HFrEF subgroup, only patient-reported anxiety improved significantly in the intervention group. Conclusions A multicomponent, behavioral intervention is associated with improvements in long-term adherence to exercise, physical function, and patient-reported outcomes in adults with HFpEF and anxiety in HFrEF. Our results provide a strong rationale for a large HFpEF clinical trial to validate these findings and examine interventional mechanisms and delivery modes that may further promote adherence and improve clinical outcomes in this population. Clinical Trial Registration : URL: https://clinicaltrials.gov/. Unique identifier: NCT01658670

Though long-neglected, the right heart (RH) is now widely accepted as a pivotal player in heart failure (HF) either with reduced (HFrEF) or preserved (HFpEF) ejection fraction. The chronic overload of the pulmonary microcirculation results in an initial phase characterized by right ventricular (RV) hypertrophy, right atrial (RA) dilation, and diastolic dysfunction. This progresses to overt right heart failure (RHF) when RV dilation and systolic dysfunction lead to RV-pulmonary arterial uncoupling with low RV output. In the context of its established relevance to progression of HF, clinicians should consider assessment of the right heart with information from clinical assessment, biomarkers, and imaging. Notably, no single parameter can predict prognosis alone in HF. Assessments should simultaneously encompass RV systolic function, pulmonary pressures, an estimation of RV-PA coupling, and right heart morphology. Despite a large volume of evidence indicating the relevance of right heart function to the clinical syndrome of HF, evidence-based management strategies are lacking. Targeting RH dysfunction in HF should be an objective of future investigations, being an unmet need in the current management of HF.

Pulmonary hypertension (PH) due to left heart disease (LHD; group 2 PH) is a common complication of heart failure with reduced ejection fraction and heart failure with preserved ejection fraction and is often related to disease severity and duration of these diseases. PH due to LHD is associated with negative impact on outcomes in addition to worse symptoms and exercise capacity. Risk factors for group 2 PH are older age, hypertension, atrial fibrillation, and features of metabolic syndrome. The main mechanisms for group 2 PH are believed to be vascular remodeling secondary to sustained elevated intravascular pressure.

Background COPD is an established predictor of clinical outcome in patients with chronic heart failure (HF). However, little evidence is available about the predictive value of FEV1 in chronic HF. Research Question Is pulmonary function related to the progression of chronic HF? Study Design and Methods The MyoVasc study ( ClinicalTrials.gov Identifier: NCT04064450) is a prospective cohort study of HF. Information on pulmonary and cardiac functional and structural status was obtained by body plethysmography and echocardiography. The primary study end point was worsening of HF. Results Overall 2,998 participants (age range, 35-84 years) with available FEV1 data were eligible for analysis. Linear multivariate regression analysis revealed an independent relationship of FEV1 (per –1 SD) with deteriorated systolic and diastolic left ventricle (LV) function as well as LV hypertrophy under adjustment of age, sex, height, cardiovascular risk factors (CVRFs), and clinical profile (LV ejection fraction: β-estimate, –1.63% [95% CI, –2.00% to –1.26%]; E/E′ ratio: β-estimate, 0.82 [95% CI, 0.64-0.99]; and LV mass/height2.7: β-estimate, 1.58 [95% CI, 1.07-2.10]; P Interpretation FEV1 represents a strong candidate to improve future risk stratification and prevention strategies in individuals with chronic, stable HF. Trial Registry ClinicalTrials.gov; No.: NCT04064450; URL: www.clinicaltrials.gov

Background Preeclampsia is associated with increased risk of future heart failure (HF), but the relationship between preeclampsia and HF subtypes are not well-established. Objectives The objective of this analysis was to identify the risk of HF with preserved ejection fraction (HFpEF) following a delivery complicated by preeclampsia/eclampsia. Methods A retrospective cohort study using the New York and Florida state Healthcare Cost and Utilization Project State Inpatient Databases identified delivery hospitalizations between 2006 and 2014 for women with and without preeclampsia/eclampsia. The authors identified women admitted for HF after discharge from index delivery hospitalization until September 30, 2015, using International Classification of Diseases-9th Revision-Clinical Modification diagnosis codes. Patients were followed from discharge to the first instance of primary outcome (HFpEF hospitalization), death, or end of study period. Secondary outcomes included hospitalization for any HF and HF with reduced ejection fraction, separately. The association between preeclampsia/eclampsia and HFpEF was analyzed using Cox proportional hazards models. Results There were 2,532,515 women included in the study: 2,404,486 without and 128,029 with preeclampsia/eclampsia. HFpEF hospitalization was significantly more likely among women with preeclampsia/eclampsia, after adjusting for baseline hypertension and other covariates (aHR: 2.09; 95% CI: 1.80-2.44). Median time to onset of HFpEF was 32.2 months (interquartile range: 0.3-65.0 months), and median age at HFpEF onset was 34.0 years (interquartile range: 29.0-39.0 years). Both traditional (hypertension, diabetes mellitus) and sociodemographic (Black race, rurality, low income) risk factors were also associated with HFpEF and secondary outcomes. Conclusions Preeclampsia/eclampsia is an independent risk factor for future hospitalizations for HFpEF.

BACKGROUND: A warmup period of “priming” exercise has been shown to improve peripheral oxygen transport in older adults. We sought to determine the acute effects of priming exercise on central hemodynamics at rest and during a repeat exercise in heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: This is a post-hoc analysis from three studies. Subjects with HFpEF (n=42) underwent cardiac catheterization with simultaneous expired gas analysis at rest and during exercise (20W for 5 minutes, “priming” exercise). Measurements were then repeated at rest and during a second bout of exercise at 20W workload (second exercise). During priming exercise, HFpEF subjects displayed dramatic increases in biventricular filling pressures and exercise-induced pulmonary hypertension. Following priming exercise at rest, biventricular filling pressures and pulmonary artery (PA) pressures were lower and lung tidal volume was increased. During the second bout of exercise, biventricular filling (PA wedge pressure, 29±8 mmHg at 2(nd) exercise vs. 32±7 mmHg at 1(st) exercise, p=0.0003) and PA pressures were lower, and PA compliance increased. CONCLUSIONS: This study shows that short duration, submaximal priming exercise attenuates the pathologic increases in filling pressures, improving pulmonary vascular hemodynamics at rest and during repeat exercise in HFpEF. CLINICAL TRIAL REGISTRATIONS: ClinicalTrials.gov identifier: NCT01932606, NCT02262078, NCT02885636.

Among heart failure (HF) patients, the onset of atrial fibrillation (AF) is often associated with a marked worsening of HF symptoms and increased morbidity and mortality. Among AF patients, 30%-40% experience at least 1 HF episode. New data suggest that, in HF patients, AF rhythm control is superior to rate control and that rhythm control by catheter ablation is superior to antiarrhythmic drugs. In recent years, several trials that addressed the impact of AF ablation on morbidity and mortality included HF patients; however, studies also have specifically investigated the growing cohort of patients suffering from both HF and AF. Although the majority of these trials showed a marked benefit of AF ablation, there are hints that not all HF patients benefit equally from AF ablation. AF treatment in HF is challenging because the same cardiac morbidities that lead to HF can also act as risk factors for the development of the arrhythmogenic substrate that causes AF. In many patients, this arrhythmogenic substrate can be successfully treated by antral pulmonary vein isolation pulmonary vein isolation (PVI). However, due to advanced atrial disease, some patients also might require multiple procedures and/or "PVI plus" ablation strategies. In this review, we summarize current data on the effect of AF ablation in HF patients, with a special focus on the beneficial effect of AF ablation in different clinical HF subgroups.

Background Diagnosing heart failure with preserved ejection fraction (HFpEF) is challenging. Although the H2FPEF score and HFA-PEFF algorithm have been proposed for diagnosing HFpEF, previous validation studies were conducted in stable chronic heart failure (HF). Moreover, information on their applicability in the Asian population is limited. We sought to investigate these scores' diagnostic performance for HFpEF in Japanese patients recently hospitalized due to acute decompensated HF. Methods We examined patients with HFpEF recently hospitalized with acute decompensated HF from a nationwide HFpEF-specific multicenter registry (HFpEF group) and control patients who underwent echocardiography to investigate the cause of dyspnea in our hospital (Non-HFpEF group). Results The studied population included 372 patients (194 HFpEF group and 178 Non-HFpEF group; HFpEF prevalence, 52%). A high H2FPEF score (6–9 points) could diagnose HFpEF with a high specificity of 97% and a positive predictive value (PPV) of 94%, and a low H2FPEF score (0–1 point) could rule out HFpEF with a high sensitivity of 97% and a negative predictive value (NPV) of 93%. HFpEF could be diagnosed with a high HFA-PEFF score (5–6 points) (specificity, 84%; PPV, 82%) or ruled out with a low HFA-PEFF score (0–1 point) (sensitivity, 99%; NPV, 89%). The H2FPEF score was significantly superior to the HFA-PEFF score in diagnostic accuracy (area under the curve: 0.89 vs. 0.82, respectively, p = 0.004). Conclusions The H2FPEF and the HFA-PEFF scores had acceptable diagnostic accuracy in diagnosing HFpEF in Japanese patients.

The diagnosis of heart failure with preserved ejection fraction is characterized by its complexity, especially for physicians without great experience in comprehensive transthoracic Doppler echocardiography. Peak mitral E-wave (E) velocity has been successfully correlated to invasive left ventricular diastolic pressures in patients with structural heart disease. The aim of the study was to address the accuracy of E in the diagnosis of heart failure with preserved ejection fraction in elderly patients with acute dyspnea.This prospective study included 29 consecutive patients ≥70 years of age with heart failure with preserved ejection fraction and acute dyspnea and 29 controls ≥70 years of age. The final diagnosis was supported by the 2016 ASE/EACVI recommendations.Mean age of the overall population was 85±7 years. E was strongly correlated with left atrial volume index (r=0.72, P0.001) and with peak velocity of tricuspid regurgitation (r=0.77, P0.001). E85cm/s was 90% sensitive and 93% specific in the diagnosis of heart failure with preserved ejection fraction (AUC, 0.95). E/e' (0.95) and E/(e'xs') (0.92) did not perform better.E/e' and E/(e'xs') provide essential diagnostic and prognostic information in heart failure with preserved ejection fraction and deserve to be included in every report of comprehensive transthoracic Doppler echocardiography. E velocity is a very simple and user-friendly parameter that can be used for the sole diagnostic purpose in elderly patients with acute dyspnea by operators without great deal of experience, such as cardiologists without formal training, emergency physicians, intensive care anesthetists, internists and geriatricians.

Heart failure with preserved ejection fraction (HFpEF) represents ∼50% of all cases of congestive heart failure (CHF) with prevalence expected to increase with aging of the population. We performed an observational study of all patients admitted to 3 hospitals in the ExcelaHealth care system, Greensburg, PA, with a primary diagnosis of HFpEF heart failure exacerbation between January 2014 and January 2017. Demographic data, laboratory results, and echocardiograms performed closest to index hospitalization were collected. A total of 487 patients were admitted with a primary diagnosis of CHF exacerbation and HFpEF, with a mean age of 80.5 years (±10.9), 62% women and predominantly Caucasian (98.8%). Over a median follow-up of 21.7 months, 246 patients died with an all-cause mortality rate of 51.3%. Receiver operator curves were generated for multiple continuous variables to identify optimal cut-off values Kaplan-Meir survival curves were then generated. Clinical factors were tested by univariate Cox regression modeling, with significant factors entered into a step-wise multivariate model. Our modeling identified age80 years, serum albumin level3.2 g/dl, N-terminal pro-brain natriuretic peptide (NT-proBNP)5,000 pg/mL and medial E/e'≥20 as significant, independent predictors of all-cause mortality (p-value0.0001). Surprisingly, lack of a diagnosis of hypertension was associated with significantly increased mortality risk. In a community-based sample of HFpEF patients, we identified multiple factors that were strong, independent predictors of all-cause mortality that can be easily applied in a clinical setting.

Heart failure with preserved ejection fraction (HFpEF) represents one of the greatest unmet needs in medicine. In the EMPEROR-Preserved trial, recently reported in the NEJM, the SGLT2 inhibitor empagliflozin reduced the primary outcome of heart failure hospitalizations and cardiovascular death by 21% in patients with HFpEF. This represents an important breakthrough in the war against heart failure.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome that has become a global health issue, with mortality ranging from 53% to 74% at 5 years. It is defined as the presence of signs and symptoms of heart failure associated with left ventricular ejection fraction greater than or equal to 50%. The definition and diagnosis of HFpEF in patients with unexplained dyspnea remain a clinical challenge in the absence of a unique diagnostic algorithm universally recognized. Clinical trials conducted so far did not show a significant improvement of prognosis, but forthcoming therapies could provide innovative solutions.

Exercise intolerance (EI) is the primary manifestation of chronic heart failure with preserved ejection fraction (HFpEF), the most common form of heart failure among older individuals. The recent recognition that HFpEF is likely a systemic, multiorgan disorder that shares characteristics with other common, difficult-to-treat, aging-related disorders suggests that novel insights may be gained from combining knowledge and concepts from aging and cardiovascular disease disciplines. This state-of-the-art review is based on the outcomes of a National Institute of Aging-sponsored working group meeting on aging and EI in HFpEF. We discuss aging-related and extracardiac contributors to EI in HFpEF and provide the rationale for a transdisciplinary, "gero-centric" approach to advance our understanding of EI in HFpEF and identify promising new therapeutic targets. We also provide a framework for prioritizing future research, including developing a uniform, comprehensive approach to phenotypic characterization of HFpEF, elucidating key geroscience targets for treatment, and conducting proof-of-concept trials to modify these targets.

Objectives The purpose of this study was to determine the relationship between the changes in diastolic function and their association with cardiac biomarkers in the perioperative period in patients undergoing complex endovascular aortic repair. Design Prospective observational study. Setting Single-center academic hospital, central teaching hospital in Warsaw, Poland. Participants The study comprised 27 high-risk patients scheduled for elective endovascular repair of aortic aneurysm. Interventions Complex endovascular procedure using branched endograft of the thoracoabdominal aorta. Branches of the stent grafts included renal arteries, the superior mesenteric artery, and the celiac trunk. Measurements and Main Results The primary outcome was to evaluate changes in diastolic function parameters assessed with transthoracic echocardiography at two and 24 hours postoperatively. The major secondary outcomes were changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin I concentrations, systolic function parameters, hemodynamic parameters at two and 24 hours, length of hospital stay, and 30-day mortality. There was a reduction in e’ wave velocity on both the septal and lateral sides at two hours compared with the baseline (p = 0.041 and p = 0.05, respectively). There was an increase in both NT-proBNP and troponin I concentrations after surgery (p = 0.002 and p = 0.034, respectively), with troponin I peaking two hours after surgery and NT-proBNP peaking 24 hours after surgery. Conclusions Patients undergoing a branched endovascular aortic repair of a thoracoabdominal aortic aneurysm experience a cardiac insult that manifests with deterioration in diastolic parameters and concomitant increases of troponin and NT-proBNP concentrations. Additional large-scale prospective studies are required to confirm this phenomenon.

Visual Abstract, Highlights • Early cardiac mitochondrial dysfunction is mediated by transcriptional down-regulation of the mitochondrial proteome. • Comprehensive metabolic remodeling is conserved throughout HFpEF progression and includes increased amino acid and lipid species, indicative of impaired oxidative metabolism. • Transcriptional and metabolic remodeling of skeletal muscle suggests cardiac signaling as a mediator of peripheral tissue maladaptation. • Unbiased systems-level analysis provides new mechanisms underlying HFpEF development., Summary In this study the authors used systems biology to define progressive changes in metabolism and transcription in a large animal model of heart failure with preserved ejection fraction (HFpEF). Transcriptomic analysis of cardiac tissue, 1-month post-banding, revealed loss of electron transport chain components, and this was supported by changes in metabolism and mitochondrial function, altogether signifying alterations in oxidative metabolism. Established HFpEF, 4 months post-banding, resulted in changes in intermediary metabolism with normalized mitochondrial function. Mitochondrial dysfunction and energetic deficiencies were noted in skeletal muscle at early and late phases of disease, suggesting cardiac-derived signaling contributes to peripheral tissue maladaptation in HFpEF. Collectively, these results provide insights into the cellular biology underlying HFpEF progression.

Background The increase in intraabdominal pressure (IAP) has been correlated with increased creatinine levels in patients with heart failure with severely reduced left ventricular ejection fraction (HFrEF). However, IAP has not been examined in more stable patients or those with heart failure with preserved ejection fraction (HFpEF). Patients and method We conducted an observational, prospective descriptive study that measured the IAP of patients hospitalised for decompensated heart failure (HF). The sample was stratified according to left ventricular ejection fraction (LVEF), with a cut-off of 50%. The objective was to analyse the IAP, the baseline characteristics and degree of congestion using clinical ultrasonography and impedance audiometry. Results The study included 56 patients, 22 with HFrEF and 34 with HFpEF. The patients with HFrEF presented a higher prevalence of ischaemic heart disease (11% vs. 6%; p = 0.010) and chronic obstructive pulmonary disease/asthma (6% vs. 2%; p = 0.025). The IAP was higher in the patients with HFrEF (17.2 vs. 13.3 mmHg; p = 0.004), with no differences in renal function at admission according to the LVEF (CKD-EPI creatinine) (HFrEF 55.0 mL/min/1.73 m2 [32.6–83.6] vs. HFpEF 55.0 mL/min/1.73 m2 [44.0–74.9]; p = 0.485). The patients with HFrEF presented a more congestive profile determined through ultrasonography (inferior vena cava collapse [26% vs. 50%; p = 0.001]), impedance audiometry (total body water at admission, 46 L vs. 41 L; p = 0.052; and at 72 h, 50.2 L vs. 39.1 L; p = 0.038) and CA125 concentration (68 U/mL vs. 39 U/mL; p = 0.037). Conclusions During the decompensation episodes, the patients with HFrEF had a greater increase in IAP and a higher degree of systemic congestion.

Heart failure with preserved ejection fraction (HFpEF) is characterized by a high rate of hospitalization and mortality (up to 84% at 5 years), which are similar to those observed for heart failure with reduced ejection fraction (HFrEF). These epidemiologic data claim for the development of specific and innovative therapies to reduce the burden of morbidity and mortality associated with this disease. Compared with HFrEF, which is due to a primary myocardial damage (eg ischemia, cardiomyopathies, toxicity), a heterogeneous etiologic background characterizes HFpEF. The authors discuss these phenotypes and specificities for defining therapeutic strategies that could be proposed according to phenotypes.

It is generally considered that obstructive sleep apnea is a potential cause of heart failure (HF), and insomnia and central sleep apnea are results of HF. However, the number of reports describing the bidirectional relationship between sleep disorder and HF has increased. Sleep disorder may contribute to left ventricular diastolic dysfunction via left atrial overload, left ventricular remodeling, pulmonary hypertension, and atrial fibrillation, which lead to HF with preserved left ventricular ejection fraction. Overnight rostral fluid shift and lung congestion may lead to airflow obstruction in the upper pharynx and stimulate pulmonary irritant receptors, which induce hyperventilation and sleep disorder.

Heart failure with preserved ejection fraction (HFpEF) is a significantly symptomatic disease and has a poor prognosis similar to that of heart failure with reduced ejection fraction (HFrEF). Contrary to HFrEF, HFpEF is difficult to diagnose, and the recommended diagnostic algorithm of HFpEF is complicated. Several therapies for HFpEF have failed to reduce mortality or morbidity. HFpEF is thought to be a complex and heterogeneous systemic disorder that has various phenotypes and multiple comorbidities. Therefore, therapeutic strategies of HFpEF need to change depending on the phenotype of the patient. This review highlights the pharmacologic and nonpharmacologic treatment of HFpEF.

The prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing rapidly, and its prognosis is as poor as that of HF with reduced EF. Hypertension is an important risk factor involved in the pathophysiology of HFpEF. Although treatment of hypertension lowers the incidence of HF and is beneficial in patients with HFpEF, there is conflicting evidence on this topic. This article discusses the pathophysiological mechanisms linking hypertension with HFpEF and also the current evidence on the treatment of hypertension in patients with HFpEF.

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome of shortness of breath and/or exercise intolerance secondary to elevated left ventricular filling pressures at rest or with exertion either as a result of primary diastolic dysfunction (primary HFpEF) or secondary to specific underlying causes (secondary HFpEF). In secondary HFpEF, early intervention of underlying valvular heart disease generally improves symptoms and prolongs survival. In primary HFpEF, there is increasing awareness of the existence and prognostic implications of secondary atrioventricular valve regurgitation. Further studies will clarify their mechanisms and the effectiveness of valvular intervention in this intriguing HFpEF subgroup.

Obese heart failure with preserved ejection fraction (HFpEF) is a distinct HFpEF phenotype. Sodium retention, high circulating neurohormone levels, alterations in energy substrate metabolism, group 3 pulmonary hypertension, pericardial restraint, and systemic inflammation are central pathophysiologic mechanisms. Confirming the diagnosis may be challenging and high suspicion is required. Reduction of visceral adipose tissue, via caloric restriction and/or bariatric surgery, may improve outcomes in obese HFpEF patients. Furthermore, mineralocorticoid receptor inhibition, neprilysin inhibition, and sodium-glucose cotransporter 2 inhibition can ameliorate the effects of adiposity on the cardiovascular system, allowing for promising new treatment targets for the obese HFpEF phenotype.

Heart failure with preserved ejection fraction (HFpEF) is a major public health problem that affects half of all patients with HF. It is rising in prevalence, is associated with high morbidity and mortality, and has very few effective treatments. HFpEF is currently understood as a heterogeneous syndrome originating from the interplay of cardiac and extracardiac abnormalities. The most important pathophysiology in patients with HFpEF is diastolic dysfunction, which presents with impairments in relaxation or increases in chamber stiffness that lead to an increase in left ventricular filling pressures at rest or during exercise that causes dyspnea.

Heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD) constitute a high-risk phenotype with significant morbidity and mortality and poor prognosis. Multiple proinflammatory comorbid conditions influence the pathogenesis of HFpEF and CKD. Renal dysfunction in HFpEF is a consequence of the complex interplay between hemodynamic factors, systemic congestion, inflammation, endothelial dysfunction, and neurohormonal mechanisms. In contrast to heart failure with reduced ejection fraction, there is a dearth of effective targeted therapies for HFpEF. Tailoring study design toward the different phenotypes and delving into their pathophysiology may be fruitful in development of effective phenotype-specific targeted pharmaceutical therapies.

Heart failure (HF) is an ongoing crisis reaching epidemic proportions worldwide. About 50% of HF patients have a preserved ejection fraction. Invasive hemodynamics have shown varied results in patients who have HF with preserved ejection fraction (HFpEF). This article attempts to summarize the importance of detecting pulmonary vascular remodeling in HFpEF using invasive hemodynamics. Incorporating newer invasive hemodynamic parameters such as diastolic pulmonary gradient, pulmonary arterial compliance, pulmonary vascular resistance, and pulmonary arterial pulsatility index may improve patient selection for studies used in defining advanced therapies and clinical outcomes. Profiling of patients using invasive hemodynamic parameters may lead to better patient selection for clinical research.

Chronic use of hydroxychloroquine can result in cardiomyopathy and conduction disturbances. Here, we describe a case of hydroxychloroquine cardiotoxicity in a patient with heart failure with preserved ejection fraction and severe chronotropic incompetence. (Level of Difficulty: Intermediate.), Central Illustration

Exertional dyspnea is the most common symptom in patients with heart failure with preserved ejection fraction; however, it is not specific to this disease. Stress testing provides crucial information about the diagnosis and prognosis of heart failure with preserved ejection before it reaches the advanced stage. Among various stress tests, noninvasive supine bicycle diastolic stress echocardiography has provided the most evidence for diagnosing and predicting the prognosis of heart failure with preserved ejection fraction. In current practice guidelines, a noninvasive or invasive diastolic stress test is recommended when a diagnosis is unclear in resting echocardiography.

Exercise intolerance represents a typical feature of heart failure with preserved ejection fraction (HFpEF), and is associated with a poor quality of life, frequent hospitalizations, and increased all-cause mortality. The cardiopulmonary exercise test is the best method to quantify exercise intolerance, and allows detection of the main mechanism responsible for the exercise limitation, influencing treatment and prognosis. Exercise training programs improve exercise tolerance in HFpEF. However, studies are needed to identify appropriate type and duration. This article discusses the pathophysiology of exercise limitation in HFpEF, describes methods of determining exercise tolerance class, and evaluates prognostic implications and potential therapeutic strategies.

INTRODUCTION: The relationship between physical activity (PA), exercise capacity, and quality of life (QOL) in obese heart failure with preserved ejection fraction (HFpEF) is poorly understood. METHODS: This was an ancillary study to a clinical trial. Accelerometers were used to measure light PA (LPA), moderate to vigorous PA (MVPA), total PA, PA energy expenditure (PAEE), and steps. Peak VO(2), exercise time, and six-minute walk distance, as well as QOL measures were obtained. Pearson correlations were performed to examine relationships between PA, exercise capacity, and QOL. RESULTS: Patients (n=58) were 68.0±5.7 years old, 78% female, 59% white, and obese (BMI 39.1±6.1 kg/m(2)). Patients had low levels of objectively measured PA as well as reduced exercise capacity and poor QOL. LPA (r=0.32, p=0.014) and steps/day (r =0.30, p=0.022) were modestly correlated with peak VO(2). All PA variables were modestly correlated with exercise time (r=0.33–0.49, all p

Case Presentation A 19-year-old pregnant woman at week 32 of gestation was referred to our clinic with progressive shortness of breath for the further evaluation and treatment of high-risk pregnancy. Her complaints had been existing since her childhood. Two years prior to her admission, she had been diagnosed with heart failure with preserved ejection fraction due to cardiomyopathy and associated pulmonary hypertension. The patient had no family history of any cardiac disease. She had never smoked or drunk alcohol. Her clinical condition had deteriorated progressively with the pregnancy.

Given the role of comorbid conditions in the pathophysiology of HFpEF, we aimed to identify and rank the importance of comorbid conditions associated with post-hospitalization outcomes of older adults hospitalized for HFpEF. We examined data from 4605 Medicare beneficiaries hospitalized in 2007–2014 for HFpEF based on ICD-9-CM codes for acute diastolic heart failure (428.31 or 428.33). To identify characteristics with high importance for prediction of mortality, all-cause rehospitalization, rehospitalization for heart failure, and composite outcome of mortality or all-cause rehospitalization up to 1 year, we developed boosted decision tree ensembles for each outcome, separately. For interpretability, we estimated hazard ratios (HRs) and 95% confidence intervals (CI) using Cox proportional hazards models. Age and frailty were the most important characteristics for prediction of mortality. Frailty was the most important characteristic for prediction of rehospitalization, rehospitalization for heart failure, and the composite outcome of mortality or all-cause rehospitalization. In Cox proportional hazards models, a 1-SD higher frailty score (0.1 on theoretical range of 0–1) was associated with a HR of 1.27 (1.06–1.52) for mortality, 1.16 (1.07–1.25) for all-cause rehospitalization, 1.24 (1.14–1.35) for HF rehospitalization, and 1.15 (1.07–1.25) for the composite outcome of mortality or all-cause rehospitalization. In conclusion, frailty is an important predictor of mortality and rehospitalization in adults aged [Formula: see text] 66 years with HFpEF.

Objectives The purpose of this study was to follow the long-term progression of diabetic cardiomyopathy by combining cardiac magnetic resonance (CMR) and molecular analysis. Background The evolution of diabetic cardiomyopathy to heart failure affects patients’morbidity and mortality. CMR is the gold standard to assess cardiac remodeling, but there is a lack of markers linked to the mechanism of diabetic cardiomyopathy progression. Methods Five-year longitudinal study on patients with type 2 diabetes mellitus (T2DM) enrolled in the CECSID (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes) trial compared with nondiabetic age-matched controls. CMR with tagging together with metabolic and molecular assessments were performed at baseline and 5-year follow-up. Results A total of 79 men (age 64 ± 8 years) enrolled, comprising 59 men with T2DM compared with 20 nondiabetic age-matched controls. Longitudinal CMR with tagging showed an increase in ventricular mass (ΔLVMi = 13.47 ± 29.66 g/m2; p = 0.014) and a borderline increase in end-diastolic volume (ΔEDVi = 5.16 ± 14.71 ml/m2; p = 0.056) in men with T2DM. Cardiac strain worsened (Δσ = 1.52 ± 3.85%; p = 0.033) whereas torsion was unchanged (Δθ = 0.24 ± 4.04°; p = 0.737), revealing a loss of the adaptive equilibrium between strain and torsion. Contraction dynamics showed a decrease in the systolic time-to-peak (ΔTtP = −35.18 ± 28.81 ms; p Conclusions Within 5 years of diabetic cardiomyopathy onset, increasing cardiac hypertrophy is associated with progressive impairment in strain, depletion of the compensatory role of torsion, and changes in viscoelastic contraction dynamics. These changes are independent of glycemic control and paralleled by the up-regulation of specific microRNAs targeting the extracellular matrix. (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes [CECSID]; NCT00692237 )

Objectives This study aimed to characterize trends in technetium Tc 99m pyrophosphate (99mTc-PYP) scanning for amyloid transthyretin cardiac amyloidosis (ATTR-CA) diagnosis, to determine whether patients underwent appropriate assessment with monoclonal protein and genetic testing, to evaluate use of single-photon emission computed tomography (SPECT) in addition to planar imaging, and to identify predictive factors for ATTR-CA. Background 99mTc-PYP scintigraphy has been repurposed for noninvasive diagnosis of ATTR-CA. Increasing use of 99mTc-PYP can facilitate identification of ATTR-CA, but appropriate use is critical for accurate diagnosis in an era of high-cost targeted therapeutics. Methods Patients undergoing 99mTc-PYP scanning 1 h after injection at a quaternary care center from 2010 to 2019 were analyzed; clinical information was abstracted; and SPECT results were analyzed. Results Over the decade, endomyocardial biopsy rates remained stable with scanning rates peaking at 132 in 2019 (p Conclusions Use of noninvasive testing with 99mTc-PYP scanning for evaluation of ATTR-CA is increasing, and the inclusion of monoclonal protein testing and SPECT imaging is crucial to rule out amyloid light chain amyloidosis and distinguish myocardial retention from blood pooling.

Almost three-quarters of all heart failure patients who are older than 65 have heart failure with preserved ejection fraction (HFpEF). The proportion and hospitalization rate of patients with HFpEF are increasing steadily relative to patients in whom heart failure occurs as result of reduced ejection fraction. The predominance of the HFpEF phenotype most likely is explained by the prevalence of medical conditions associated with an aging population. A multitude of age-related, medical, and lifestyle risk factors for HFpEF have been identified as potential causes for the sustained low-grade proinflammatory state that accelerates disease progression. Profound left ventricular (LV) systolic and diastolic stiffening, elevated LV filling pressures, reduced arterial compliance, left atrial hypertension, pulmonary venous congestion, and microvascular dysfunction characterize HFpEF, but pulmonary arterial hypertension, right ventricular dilation and dysfunction, and atrial fibrillation also frequently occur. These cardiovascular features make patients with HFpEF exquisitely sensitive to the development of hypotension in response to acute declines in LV preload or afterload that may occur during or after surgery. With the exception of symptom mitigation, lifestyle modifications, and rigorous control of comorbid conditions, few long-term treatment options exist for these unfortunate individuals. Patients with HFpEF present for surgery on a regular basis, and anesthesiologists need to be familiar with this heterogeneous and complex clinical syndrome to provide successful care. In this article, the authors review the diagnosis, pathophysiology, and treatment of HFpEF and also discuss its perioperative implications.

The effect of sacubitril-valsartan in heart failure patients with mid-range (HFmEF) and preserved (HFpEF) ejection fractions remains unclear. This study aimed to investigate the clinical benefits of sacubitril-valsartan in HFmEF and HFpEF patients.PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure were searched from inception to 29 February 2020 to identify pertinent articles. Studies meeting the inclusion criteria were included and analysed.Six (6) studies, with a total of 5,503 patients, were included. Compared with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, sacubitril-valsartan significantly reduced the rate of HF hospitalisation (risk ratios, 0.84; 95% CI, 0.77-0.91; p0.001) and improved the New York Heart Association class (risk ratios, 1.25; 95% CI, 1.10-1.43; p=0.001) in HFmEF and HFpEF patients. Both the cardiovascular mortality and all-cause mortality were not significantly decreased by sacubitril-valsartan. In addition, there were no significant between-group differences in the N-terminal pro-B-type natriuretic peptide and left ventricular ejection fraction changes. Regarding safety, sacubitril-valsartan was likely to increase the risk of hypotension, but the incidence of serum creatinine elevation was significantly lower in the sacubitril-valsartan group than in the angiotensin-converting enzyme inhibitors and angiotensin receptor blockers group.This meta-analysis suggests that sacubitril-valsartan may be an effective and safe strategy with which to improve the clinical symptoms and reduce HF hospitalisation in HFmEF and HFpEF patients.

Obesity is common in heart failure with preserved ejection fraction (HFpEF). Whether obesity modifies the response to spironolactone in patients with HFpEF remains unclear. We aimed to investigate the effect of obesity, defined by body mass index (BMI) and waist circumference (WC), on response to spironolactone in patients with HFpEF enrolled in Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial. This was a post-hoc, exploratory analysis of the Americas cohort of Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial. BMI≥30 kg/m2 was used to define the obese group and WC≥102 cm in men and ≥88 cm in women were defined as high WC. In separate analyses, BMI and WC were treated as continuous variables. The effect of spironolactone versus placebo on outcomes was calculated by BMI and WC using Cox proportional hazard models. Obese patients were younger and had more co-morbidities. In multivariate analysis, spironolactone use was associated with a significant reduction in the primary end point, compared with placebo in obese [hazard ratio (HR = 0.618, 95% CI 0.460 to 0.831, p = 0.001), but not in nonobese subjects (HR = 0.946, 95% CI 0.623 to 1.437, p = 0.796; p for interaction = 0.056). There was a linear association between continuous BMI and the effect of spironolactone, with the effect becoming significant at 33kg/m2. Similar results were obtained for the WC-based analysis. In conclusion, use of spironolactone in obese patients with HFpEF was associated with a decreased risk of the primary end point, cardiovascular death and HF hospitalizations, compared with placebo. Further prospective randomized studies in obese subjects are required.

Objectives The purpose of this study was to evaluate the effects of intravenous levosimendan on hemodynamics and 6-min walk distance (6MWD) in patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF). Background There are no proven effective treatments for patients with PH-HFpEF. Methods Patients with mean pulmonary artery pressure (mPAP) ≥35 mm Hg, pulmonary capillary wedge pressure (PCWP) ≥20 mm Hg, and LVEF ≥40% underwent 6MWD and hemodynamic measurements at rest, during passive leg raise, and supine cycle exercise at baseline and after an open-label 24-h levosimendan infusion (0.1 μg/kg/min). Hemodynamic responders (those with ≥4 mm Hg reduction of exercise-PCWP) were randomized (double blind) to weekly levosimendan infusion (0.075 to 0.1ug/kg/min for 24 h) or placebo for 5 additional weeks. The primary end point was exercise-PCWP, and key secondary end points included 6MWD and PCWP measured across all exercise stages. Results Thirty-seven of 44 patients (84%) met responder criteria and were randomized to levosimendan (n = 18) or placebo (n = 19). Participants were 69 ± 9 years of age, 61% female, and with resting mPAP 41.0 ± 9.3 mm Hg and exercise-PCWP 36.8 ± 11.3 mm Hg. Compared with placebo, levosimendan did not significantly reduce the primary end point of exercise-PCWP at 6 weeks (−1.4 mm Hg; 95% confidence interval [CI]: −7.8 to 4.8; p = 0.65). However, levosimendan reduced PCWP measured across all exercise stages (−3.9 ± 2.0 mm Hg; p = 0.047). Levosimendan treatment resulted in a 29.3 m (95% CI: 2.5 to 56.1; p = 0.033) improvement in 6MWD compared with placebo. Conclusions Six weeks of once-weekly levosimendan infusion did not affect exercise-PCWP but did reduce PCWP incorporating data from rest and exercise, in tandem with increased 6MWD. Further study of levosimendan is warranted as a therapeutic option for PH-HFpEF. (Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF [HELP]; NCT03541603 )

Background Early, noninvasive identification of patients with heart failure with preserved ejection fraction (HFpEF) with congestion may allow timely tailoring of decongestive therapies. The 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines provide an algorithm to assess for elevated left atrial pressure (LAP); the associations of echocardiographic LAP with clinical status and disease progression in patients with HFpEF are unclear. Methods Participants in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF trial were categorized into one of four prespecified guideline-based echocardiographic LAP categories: (1) normal, (2) elevated, (3) atrial fibrillation (AF) at the time of echocardiography, or (4) indeterminate. Associations of echocardiographic LAP categories with baseline exercise capacity, change in exercise capacity, and change in N-terminal pro–B-type natriuretic peptide over 24 weeks were evaluated. Results Of 216 participants, 199 underwent mitral inflow Doppler echocardiography for LAP categorization. Participants with elevated echocardiographic LAP (n = 81) or AF (n = 57) were older and had a higher prevalence of kidney dysfunction. Compared with the normal echocardiographic LAP group (n = 28), elevated echocardiographic LAP and AF were each independently associated with a greater reduction in peak oxygen consumption over 24 weeks after adjusting for baseline values and clinical covariates (β for elevated echocardiographic LAP = −1.55 [95% CI, −2.59 to −0.51], P = .004; β for AF = −1.33 [95% CI, −2.49 to −0.17], P = .03). Indeterminate echocardiographic LAP (n = 33) was also independently associated with a reduction in exercise capacity at 24 weeks compared with normal echocardiographic LAP (β = −1.35; 95% CI, −2.51 to −0.19; P = .02). Finally, elevated echocardiographic LAP and AF were significantly associated with increases in N-terminal pro–B-type natriuretic peptide over 24 weeks compared with normal echocardiographic LAP. Conclusions In patients with chronic HFpEF, elevated echocardiographic LAP and indeterminate echocardiographic LAP, as defined by contemporary guidelines, and AF were each independently associated with a reduction in exercise capacity compared with normal echocardiographic LAP. These findings suggest the potential utility of noninvasive LAP assessment in patients with HFpEF for tailoring treatments that decrease congestion.

Objectives This study investigated the prognostic importance of heart failure (HF) signs and symptoms in patients with heart failure and preserved ejection fraction (HFpEF), and the effect of sacubitril/valsartan on HF signs and symptoms. Background In patients with HFpEF, worsening of HF symptoms, as a marker of cardiac decompensation, is frequently the reason for hospitalization. In this heterogenous disease entity, the prognostic value of HF signs and symptoms with regard to cardiovascular (CV) outcomes is poorly defined. Methods The authors examined the association between baseline HF signs and symptoms (rest dyspnea, exertional dyspnea, paroxysmal nocturnal dyspnea, orthopnea, fatigue, edema, jugular venous distension, rales, and third heart sound) as well as burden of these HF signs and symptoms (classified as ≤2 and ≥3 HF signs and symptoms) and the primary composite of total HF hospitalizations and CV death, its components, and all-cause death in 4,725 patients enrolled in PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in HFpEF) with available signs and symptoms at randomization. Response to sacubitril/valsartan on the basis of the presence of signs and symptoms was evaluated. Effects of sacubitril/valsartan on signs and symptoms over time were assessed using binary repeated-measures logistic regression. Results Patients with high (≥3) burden of HF signs and symptoms (n = 1,772 [38%]) were more commonly women, had slightly lower left ventricular ejection fractions, higher body mass index, and more advanced New York Heart Association functional class compared with patients with low (≤2) burden (n = 2,953 [62%]) (p Conclusions High burden of HF signs and symptoms, particularly the presence of orthopnea and rales, portends a higher risk for adverse CV events in patients with HF with preserved ejection fraction. Sacubitril/valsartan did not significantly decrease the burden of HF signs and symptoms over time but did reduce exertional dyspnea relative to valsartan. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711 )

BACKGROUND Mechanisms of exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF) are not well understood. Pulmonary hypertension, a common accompaniment in patients with HFpEF, is associated with poor outcomes. While Endothelin -1 (ET-1) plays a mechanistic role in pulmonary hypertension, its role in exercise intolerance in HFpEF is not well established. OBJECTIVE To explore the association between plasma ET-1 levels and maximal oxygen consumption (pVO2), and their changes over 24 weeks in HFpEF. METHODS This is a post-hoc analysis of the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial. We performed linear regressions to assess the relationship between plasma ET-1 and pVO2. We also used linear regressions to determine whether ET-1 was associated with change in peak VO2 (ΔpVO2). RESULTS A total of 210 patients were included. Baseline plasma ET-1 levels were associated with older age, higher NT-proBNP levels, higher serum creatinine levels, and higher prevalence of atrial fibrillation. Patients with higher ET1 levels also had higher plasma galectin-3 and CITP levels. After multiple adjustments, baseline ET1 levels were associated with lower pVO2 (β -0.927, SE 0.196, p

Background Few studies have investigated right atrial (RA) remodeling in heart failure (HF) with preserved ejection fraction (HFpEF). This study sought to characterize the RA remodeling in HFpEF and to determine its prognostic significance. Methods and Results Patients with HFpEF were classified based on the presence of RA enlargement (RA volume index >39 mL/m2 in men and >33 mL/m2 in women). Compared with patients with normal RA size (n = 234), patients with RA dilation (n = 67) showed a higher prevalence of atrial fibrillation (AF), worse right ventricular systolic function, more severe pulmonary hypertension, and a greater prevalence of mild tricuspid regurgitation, as well as impaired RA reservoir function, with increased hepatobiliary enzyme levels. AF was strongly associated with the presence of RA dilation (odds ratio [OR] 10.2, 95% confidence interval [CI] 4.00–26.1 in current AF vs no AF and odds ratio 3.38, 95% CI 1.26–9.07, earlier AF vs no AF). Patients with RA dilation had more than a two-fold increased risk of composite outcomes of all-cause mortality or HF hospitalization (adjusted hazard ratio 2.01, 95% CI 1.09–3.70, P = .02). The presence of RA dilation also displayed an additive prognostic value over left atrial dilation alone. Conclusions These data demonstrate that HFpEF with RA remodeling is associated with distinct echocardiographic features characterizing advanced right heart dysfunction with an increased risk of adverse outcomes.