Acute Heart Failure With Preserved Ejection Fraction Research Articles

Comparison of clinical characteristics and prognostic factors in patients with heart failure with preserved ejection fraction with and without renal dysfunction.

Heart failure with preserved ejection fraction (HFpEF) with renal dysfunction (RD) is considered to be a specific phenotype of HFpEF. This study aimed to compare the clinical characteristics and prognostic factors for in-hospital mortality between HFpEF-diagnosed patients with and without RD. This multicenter retrospective study included 5867 consecutive patients with acute HFpEF. RD was defined by an estimated glomerular filtration rate (eGFR) of <60 mL/min per 1.73 m2. Kaplan-Meier survival curves and log-rank tests were used to compare the in-hospital mortality between the groups. Univariable and multivariable Cox regression analyses were performed to identify significant prognostic factors. Across the study cohort, 68% of patients had RD. In-hospital mortality was significantly higher in HFpEF patients with RD than in those without RD. The comorbidities and laboratory data differed significantly between the groups. Independent prognostic factors for in-hospital mortality in the HFpEF patients with RD were age (hazard ratio [HR], 1.039), systolic blood pressure (HR, 0.991), eGFR (HR, 0.981), C-reactive protein (CRP; HR, 1.028), diuretics (HR, 0.374), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACE-I/ARBs; HR, 0.680), and beta-blockers (HR, 0.662). In HFpEF patients without RD, age (HR, 1.039), systolic blood pressure (HR, 0.979), and ACE-I/ARBs (HR, 0.373) were independent prognostic factors. Significant differences in the clinical characteristics and prognostic factors, such as CRP and beta-blockers, were observed between the HFpEF patients with and without RD. These results have implications for future research and may help guide individualized patient management strategies.

Relationship of interleukin-16 with different phenogroups in acute heart failure with preserved ejection fraction.

Interleukin-16 (IL-16) has been reported to mediate left ventricular myocardial fibrosis and stiffening in patients with heart failure with preserved ejection fraction (HFpEF). We sought to elucidate whether IL-16 has a distinct impact on pathophysiology and prognosis across different subphenotypes of acute HFpEF. We analysed 211 patients enrolled in a prospective multicentre registry of acute decompensated HFpEF for whom serum IL-16 levels after stabilization were available (53% female, median age 81 [interquartile range 75-85] years). We divided this sub-cohort into four phenogroups using our established clustering algorithm. The study endpoint was all-cause death. Patients were subclassified into phenogroup 1 ('rhythm trouble' [n=69]), phenogroup 2 ('ventricular-arterial uncoupling' [n=49]), phenogroup 3 ('low output and systemic congestion' [n=41]), and phenogroup 4 ('systemic failure' [n=52]). After a median follow-up of 640days, 38 patients had died. Among the four phenogroups, phenogroup 2 had the highest IL-16 level. The IL-16 level showed significant associations with indices of cardiac hypertrophy, diastolic dysfunction, and congestion only in phenogroup 2. Furthermore, the IL-16 level had a significant predictive value for all-cause death only in phenogroup 2 (C-statistic 0.750, 95% confidence interval 0.606-0.863, P=0.017), while there was no association between the IL-16 level and the endpoint in the other phenogroups. Our results indicated that the serum IL-16 level had a significant association with indices that reflect the pathophysiology and prognosis of HFpEF in a specific phenogroup in acute HFpEF.

Triglyceride glucose index, a novel marker of insulin resistance, predicts outcomes in patients with heart failure with preserved ejection fraction

Abstract Background Insulin resistance (IR) is a characteristic feature of heart failure (HF), and it is present both in diabetic- and non-diabetic patients with HF. It is observed in patients with HF with preserved ejection fraction (HFpEF) as well as in those with HF with reduced ejection fraction (HFrEF). It is still not fully understood how IR can affect the clinical outcome in patients with HFpEF. Triglyceride glucose index (TyG index) is a novel, simple marker of IR which is well correlated with HOMA-IR. Purpose To investigate the correlation between TyG index and clinical outcome in patients with hospitalized HFpEF. Methods We enrolled 1231 patients registered in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study, which is a multicenter registration of patients hospitalized for acute decompensated HFpEF, for the present study. TyG index was calculated as Ln(serum triglyceride [mg/dL] x fasting blood glucose [mg/dL]/2) using blood sample before discharge. We followed the study patients for median of 387 days (IQR 239-727 days) to observe all-cause death and the major adverse cardiovascular events (MACE; composite of death, heart failure hospitalization and stroke). Results We could calculate TyG index in 917 patients (81±9 year old, 55.3% female) with the mean value of 8.5±1.5. Diabetes was observed in 360 (39.3%) patients, and they had higher TyG index than non-diabetic patients (8.8±0.6 vs. 8.4±.05, p&amp;lt;0.0001). Cox proportional hazard model selected TyG index score as an independent predictor for all-cause death regardless of history of diabetes, hypertension and dyslipidemia (p=0.004). We divided patients into 4 groups based on TyG index. Kaplan-Meier curves indicated the difference in all-cause mortality among 4 groups (Figure Left, p=0.0003 by log-rank test). Incidence of MACE was also significantly different among 4 groups (Figure Right, p=0.007 by log-rank test). Conclusion TyG index predicted all-cause mortality and MACE in patients with HFpEF regardless of diabetic state.Kaplan-Meier curves for death and MACE

Pathophysiological insights into machine-learning-based subphenotypes of acute heart failure with preserved ejection fraction: a biomarker analysis of PURSUIT-HFpEF registry

Abstract Background Our understanding of heart failure with preserved ejection fraction (HFpEF) has evolved from mere left ventricular diastolic dysfunction to a multiorgan disease. Purpose This study aimed to investigate the heterogeneous pathophysiology of the several phenotypes of HFpEF with multiple biomarker data. Methods This study is a post-hoc analysis of the PURSUIT-HFpEF study (N=1,231), an ongoing, prospective, multi-referral center, observational study of acute decompensated HFpEF [UMIN000021831]. In this registry, there is a pre-defined sub-cohort in which we perform multi-biomarker tests (N=212). We applied the machine-learning-based clustering model that we have previously established to the sub-cohort and classified them into 4 phenotypes: phenotype 1 labeled as "rhythm trouble" (n=69), phenotype 2 "ventricular-arterial uncoupling" (n=49), phenotype 3 "low output and systemic congestion" (n=41), and phenotype 4 "systemic failure" (n=53). Characteristics of biomarker tests in each phenotype were evaluated. Results The phenotype 2 characterized by hypertension and cardiac hypertrophy showed the highest value of N-terminal pro-brain natriuretic peptide (NT-proBNP), IL-16, high-sensitive C-reactive protein (CRP), tumor necrosis factor (TNF)-α, growth differentiation factor (GDF)-15, troponin T, and cystatin C, whereas the phenotype 1 presented the lowest value of these markers. The phenotype 3 showed the second highest value of GDF-15 and cystatin C. The phenotype 4 presented a low NT-proBNP value and a relatively high GDF-15. Conclusions The specific characteristics of biomarkers in each phenotype confirmed the validity of the machine learning model-based classification. The contribution of inflammation to the pathogenesis considerably differed in different HFpEF phenotypes. Systemic inflammation substantially contributes to the pathophysiology of the classical HFpEF phenotype with cardiac hypertrophy.

Pathophysiological insights into machine learning-based subphenotypes of acute heart failure with preserved ejection fraction

ObjectiveThe heterogeneous pathophysiology of the diverse heart failure with preserved ejection fraction (HFpEF) phenotypes needs to be examined. We aim to assess differences in the biomarkers among the phenotypes of...

Different right ventricular dysfunction and pulmonary coupling in acute heart failure according to the left ventricular ejection fraction

BackgroundRight ventricular (RV) dysfunction and pulmonary uncoupling are two acknowledged features associated with poor outcome, however few data defined RV adaptation across the different left ventricular ejection fraction (EF) cut-off. Additionally, less data are reported in patients with acute heart failure (AHF). AimsThe aim of present study was to analyse RV function in AHF patients presenting with either reduced or preserved EF. MethodsThis is a multi-center observational study including 380 patients affected by AHF: 235 had AHF with reduced EF (AHFrEF) and 145 had AHF with preserved EF (AHFpEF). Pulmonary artery systolic pressure (PASP), tricuspid annular plane systolic excursion (TAPSE), S′ wave velocity, and the RV end-diastolic diameter (RVEDD) were measured by echocardiography. TAPSE/PASP and S′/PASP ratios were calculated as non-invasive surrogates of RV-pulmonary arterial coupling. ResultsFactors associated with poor outcome were higher values of PASP (45 [40–55] mmHg vs 40 [35–46] mmHg; p < 0.001), RVEDD (44 [38–47] mm vs 37 [35–42] mm; p < 0.001), lower TAPSE values (17 [15–20] mm vs 20 [18–22] mm; p < 0.001) and S′ wave (10 [8–12] cm/s vs 11 [10–13] cm/s; p < 0.001), reduced TAPSE/PASP (0.37 [0.29–0.47] vs 0.50 [0.40–0.60]; p < 0.001) and S′/PASP ratios (0.22 [0.18–0.28] vs 0.28 [0.22–0.34]; p < 0.001). However, the prognostic parameters differed according to the LVEF value: in AHFpEF S′/PASP between 0.22 and 0.29 and > 0.29 demonstrated a protective prognostic value (Respectively HR 0.29 (0.16–0.53), p < 0.001 and HR 0.22 [0.12–0.42], p < 0.001). Conversely, in AHFrEF, TAPSE <16 mm (HR 2.59 [1.67–4.03], p < 0.001), ICV > 21 mm (HR 1.17 [1.17–1.28], p = 0.001) and TAPSE/PASP <0.49 HR 1.92 [1.10–3.37], p = 0.023) were related to adverse outcome. ConclusionsRV adaptation and RV pulmonary coupling differ in AHF according to the level of LVEF. S′ wave, and S′/PASP are associated with adverse outcome in patients with preserved EF; reduced TAPSE and TAPSE/PASP are better prognostic predictors in patients with reduced EF.

Right ventricular-arterial uncoupling as an independent prognostic factor in acute heart failure with preserved ejection fraction accompanied with coronary artery disease.

Right ventricular (RV)-arterial uncoupling is a powerful independent predictor of prognosis in heart failure with preserved ejection fraction (HFpEF). Coronary artery disease (CAD) can contribute to the pathophysiological characteristics of HFpEF. This study aimed to evaluate the prognostic value of RV-arterial uncoupling in acute HFpEF patients with CAD. This prospective study included 250 consecutive acute HFpEF patients with CAD. Patients were divided into RV-arterial uncoupling and coupling groups by the optimal cutoff value, based on a receiver operating characteristic curve of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP). The primary endpoint was a composite of all-cause death, recurrent ischemic events, and HF hospitalizations. TAPSE/PASP ≤0.43 provided good accuracy in identifying patients with RV-arterial uncoupling (area under the curve, 0.731; sensitivity, 61.4%; and specificity, 76.6%). Of the 250 patients, 150 and 100 patients could be grouped into the RV-arterial coupling (TAPSE/PASP >0.43) and uncoupling (TAPSE/PASP ≤0.43) groups, respectively. Revascularization strategies were slightly different between groups; the RV-arterial uncoupling group had a lower rate of complete revascularization (37.0% [37/100] vs . 52.7% [79/150], P <0.001) and a higher rate of no revascularization (18.0% [18/100] vs . 4.7% [7/150], P <0.001) compared to the RV-arterial coupling group. The cohort with TAPSE/PASP ≤0.43 had a significantly worse prognosis than the cohort with TAPSE/PASP >0.43. Multivariate Cox analysis showed TAPSE/PASP ≤0.43 as an independent associated factor for the primary endpoint, all-cause death, and recurrent HF hospitalization (hazard ratios [HR]: 2.21, 95% confidence interval [CI]: 1.44-3.39, P <0.001; HR: 3.32, 95% CI: 1.30-8.47, P = 0.012; and HR: 1.93, 95% CI: 1.10-3.37, P = 0.021, respectively), but not for recurrent ischemic events (HR: 1.48, 95% CI: 0.75-2.90, P = 0.257). RV-arterial uncoupling, based on TAPSE/PASP, is independently associated with adverse outcomes in acute HFpEF patients with CAD.

Long-term outcomes in heart failure with preserved ejection fraction: Predictors of cardiac and non-cardiac mortality.

Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with cardiovascular (CV) and non-CV events, but long-term risk is poorly studied. We assessed incidence and predictors of the long-term CV and non-CV events. Patients presenting with acute HF, EF≥45%, and N-terminal pro-brain natriuretic peptide>300ng/L were enrolled in the Karolinska-Rennes study in 2007-11 and were reassessed after 4-8weeks in a stable state. Long-term follow-up was conducted in 2018. The Fine-Gray sub-distribution hazard regression was used to detect predictors of CV and non-CV deaths, investigated separately from baseline acute presentation (demographic data only) and from the 4-8week outpatient visit (including echocardiographic data). Of 539 patients enrolled [median age 78 (interquartile range: 72-84) years; 52% female], 397 patients were available for the long-term follow-up. Over a median follow-up time from acute presentation of 5.4 (2.1-7.9) years, 269 (68%) patients died, 128 (47%) from CV and 120 (45%) from non-CV causes. Incidence rates per 1000 patient-years were 62 [95% confidence interval (CI) 52-74] for CV and 58 (95% CI 48-69) for non-CV death. Higher age and coronary artery disease (CAD) were independent predictors of CV death, and anaemia, stroke, kidney disease, and lower body mass index (BMI) and sodium concentrations of non-CV death. From the stable 4-8week visit, anaemia, CAD, and tricuspid regurgitation (>3.1m/s) were independent predictors of CV death, and higher age of non-CV death. In patients with acute decompensated HFpEF, over 5years of follow-up, nearly two-thirds of patients died, half from CV and the other half from non-CV causes. CAD and tricuspid regurgitation were associated with CV death. Stroke, kidney disease, lower BMI, and lower sodium were associated with non-CV death. Anaemia and higher age were associated with both outcomes. [Correction added on 24 March 2023, after first online publication: In the first sentence of the Conclusions, 'two-thirds' has been inserted before 'of patients died...' in this version.].

FK506-Binding Protein like (FKBPL) Has an Important Role in Heart Failure with Preserved Ejection Fraction Pathogenesis with Potential Diagnostic Utility.

Heart failure (HF) is the leading cause of hospitalisations worldwide, with only 35% of patients surviving the first 5 years after diagnosis. The pathogenesis of HF with preserved ejection fraction (HFpEF) is still unclear, impeding the implementation of effective treatments. FK506-binding protein like (FKBPL) and its therapeutic peptide mimetic, AD-01, are critical mediators of angiogenesis and inflammation. Thus, in this study, we investigated-for the first time-FKBPL's role in the pathogenesis and as a biomarker of HFpEF. In vitro models of cardiac hypertrophy following exposure to a hypertensive stimulus, angiotensin-II (Ang-II, 100 nM), and/or AD-01 (100 nM), for 24 and 48 h were employed as well as human plasma samples from people with different forms of HFpEF and controls. Whilst the FKBPL peptide mimetic, AD-01, induced cardiomyocyte hypertrophy in a similar manner to Ang-II (p < 0.0001), when AD-01 and Ang-II were combined together, this process was abrogated (p < 0.01-0.0001). This mechanism appears to involve a negative feedback loop related to FKBPL (p < 0.05). In human plasma samples, FKBPL concentration was increased in HFpEF compared to controls (p < 0.01); however, similar to NT-proBNP and Gal-3, it was unable to stratify between different forms of HFpEF: acute HFpEF, chronic HFpEF and hypertrophic cardiomyopathy (HCM). FKBPL may be explored for its biomarker and therapeutic target potential in HFpEF.

Pulmonary Artery Systolic Pressure and Cava Vein Status in Acute Heart Failure with Preserved Ejection Fraction: Clinical and Prognostic Implications

Peak tricuspid regurgitation (TR) velocity and inferior cava vein (ICV) distention are two recognized features of increased pulmonary artery pressure (PASP) and right atrial pressure, respectively. Both parameters are related to pulmonary and systemic congestion and adverse outcomes. However, few data exist about the assessment of PASP and ICV in acute patients affected by heart failure with preserved ejection fraction (HFpEF). Thus, we investigated the relationship existing among clinical and echocardiographic features of congestion, and we analyzed the prognostic impact of PASP and ICV in acute HFpEF patients. We analyzed clinical congestion PASP and ICV value in consecutive patients admitted in our ward by echocardiographic examination using peak Doppler velocity tricuspid regurgitation and ICV diameter and collapse for the assessment of PASP and ICV dimension, respectively. A total of 173 HFpEF patients were included in the analysis. The median age was 81 and median left ventricular ejection fraction (LVEF) was 55% [50-57]. Mean values of PASP was 45 mmHg [35-55] and mean ICV was 22 [20-24] mm. Patients with adverse events during follow-up showed significantly higher values of PASP (50 [35-55] vs. 40 [35-48] mmHg, (p = 0.005) and increased values of ICV (24 [22-25] vs. 22 [20-23] mm, p < 0.001). Multivariable analysis showed prognostic power of ICV dilatation (HR 3.22 [1.58-6.55], p = 0.001) and clinical congestion score ≥ 2 (HR 2.35 [1.12-4.93], p = 0.023), but PASP increase did not reach statistical significance (p = 0.874). The combination of PASP > 40 mmHg and ICV > 21 mm was capable of identifying patients with increased events (45% vs. 20%). ICV dilatation provides additional prognostic information with respect to PASP in patients with acute HFpEF. A combined model adding PASP and ICV assessment to clinical evaluation is a useful tool for predicting HF related events.

Red cell distribution width (RDW) is correlated to time of oxygen desaturation < 90% and length of sleep apneas in patients with sleep disorder breathing (SDB) and acute heart failure with preserved ejection fraction (HFpEF).

Heart failure with preserved ejection fraction (HFpEF) is very frequently associated to sleep breathing disorders (SDB). Red blood cell distribution width (RDW) has been shown to be a potential inflammatory index linked to the degree of hypoxia and oxidative stress. To identify the existence of a possible relationship between sleep apnea, oxygen saturation (SaO2) and RDW in a population of subjects affected by acute HFpEF (AHFpEF). AHFpEF patients with known history of SDB were enrolled and performed blood chemistry, echocardiography, and 24-h polysomnography (PSG). A total of 34 acute HFpEF patients (mean age 72.8 +/-8.63) were enrolled in the study. A control group of 24 non-HF patients were considered. Compared to controls, HFpEF patients showed a higher mean apnea hypopnea index (AHI), with prevalence of central apneas. A moderate to severe desaturation pattern was observed in AHFpEF vs. controls. RDW was significantly higher in AHFpEF patients vs. controls (mean value 14.7 +/-2.6 % vs. 9.1 +/-2.2, p < 0.05). In AHFpEF, RDW showed a positive correlation with time of SaO2 < 90% (r = 0.35, p = 0.04), and with mean length of apneic events (60 +/-28 s, r = 0.29, p = 0.03). In patients with AHFpEF and SDB, a dependence relationship between RDW and duration of oxygen desaturation was observed, as if oxidative stress and inflammation related to RDW increase could also be linked to severity of sleep disorders in this population.

Systemic Biomarkers and Unique Pathways in Different Phenotypes of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) accounts for around 50% of all heart failure cases. It is a heterogeneous condition with poorly understood pathogenesis. Here, we aimed to identify unique pathogenic mechanisms in acute and chronic HFpEF and hypertrophic cardiomyopathy (HCM). We performed unbiased, comprehensive proteomic analyses of plasma samples from gender- and BMI-matched patients with acute HFpEF (n = 8), chronic HFpEF (n = 9) and HCM (n = 14) using liquid chromatography–mass spectrometry. Distinct molecular signatures were observed in different HFpEF forms. Clusters of biomarkers differentially abundant between HFpEF forms were predominantly associated with microvascular inflammation. New candidate protein markers were also identified, including leucine-rich alpha-2-glycoprotein 1 (LRG1), serum amyloid A1 (SAA1) and inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3). Our study is the first to apply systematic, quantitative proteomic screening of plasma samples from patients with different subtypes of HFpEF and identify candidate biomarkers for improved management of acute and chronic HFpEF and HCM.

Relation of lymphopenia to comorbidity burden and its prognostic value in patients with acute decompensated heart failure with preserved left ventricular ejection fraction: a multicentre study

Abstract Background Systemic inflammation resulting from comorbidities is postulated to play a central role in the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). Lymphopenia is a common manifestation of systemic inflammation and a prognostic factor in patients with HF. However, the association of lymphopenia with the comorbidity burden is unknown, and its prognostic value in patients with HFpEF admitted due to acute decompensated heart failure (ADHF) also remains elusive. Purpose We sought to clarify the relation of lymphopenia with the comorbidity burden, as well as its prognostic value and complementarity with the Get with the Guidelines-Heart Failure (GWTG-HF) risk score in ADHF patients with HFpEF. Methods Patients' data were extracted from the Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT-HFpEF), which is a prospective multicentre registry for patients with ADHF with a LVEF ≥50%. We analysed data of patients admitted between June 2016 and December 2020 who survived to discharge. The total lymphocyte count (per μL) and GWTG-HF risk score were obtained on admission, as previously reported. Comorbidity burden was defined as the number of comorbidities from the following: atrial fibrillation, hypertension, diabetes mellitus, coronary artery disease, chronic kidney disease, chronic obstructive pulmonary disease, anaemia, and obesity. The study endpoint was all-cause death. Results Over a median follow-up of 417 days, 181 of the 1013 included patients died. The proportion of patients with a total lymphocyte count in the lowest tertile was increasing with the increase in comorbidity burden (Figure 1). In the multivariate Cox analysis, a total lymphocyte count in the intermediate (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.00–2.41, p=0.0486) and lowest tertile (HR 2.23, 95% CI 1.47–3.38, p=0.0002) was independently associated with all-cause death. There was a significant difference in the all-cause death rate among the groups stratified by total lymphocyte count tertile (Figure 2). The total lymphocyte count had a higher C-statistic value (0.627) for the prediction of all-cause death than the GWTG-HF risk score, and the C-statistic value of the GWTG-HF risk score was improved when the total lymphocyte count was added (0.613 to 0.636, p=0.0260). Conclusions Lymphopenia was significantly associated with comorbidity burden. Furthermore, it was a useful marker of poor prognosis in hospitalised patients with acute HFpEF and was shown to be complementary to the contemporary HF prognostic score. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Roche Diagnostics K.K.Fuji Film Toyama Chemical Co. Ltd.

Right and left ventricular structures and functions in acute HFpEF: comparing the hypertensive pulmonary edema and worsening heart failure phenotypes.

Limited data are available on right (RV) and left (LV) ventricular structures and functions in acute heart failure with preserved ejection fraction (AHF-pEF) presenting with hypertensive pulmonary edema (APE) versus predominant peripheral edema (peHF). In a prospective study of consecutive patients with AHF-pEF, 80 patients met inclusion and not exclusion criteria, and underwent echocardiographic and laboratory examination in the emergency ward. The survived (94%) were re-evaluated at the discharge. At admission, systolic, diastolic, pulse blood pressure (BP), and high sensitivity troponin I were higher (all P < 0.05) with APE than with peHF while brain-type natriuretic peptide (BNP), hemoglobin and estimated glomerular filtration rate (eGFR) did not differ between the two phenotypes. LV volumes and EF were comparable between APE and peHF, but APE showed lower relative wall thickness (RWT), smaller left atrial (LA) volume, higher pulse pressure/stroke volume (PP/SV), and higher ratio between the peak velocities of the early diastolic waves sampled by traditional and tissue Doppler modality (mitral E/e', all P < 0.05). Right ventricular and atrial (RA) areas were smaller, tricuspid anular plane systolic excursion (TAPSE) and estimated pulmonary artery peak systolic pressure (sPAP) were higher with APE than with peHF (all P < 0.05) while averaged degree of severity of tricuspid insufficiency was greater with peHF than with APE. At discharge, PP/SV, mitral E/e', sPAP, RV sizes were reduced from admission in both phenotypes (all P < 0.05) and did not differ anymore between phenotypes, whereas LV EF and TAPSE did not show significant changes over time and treatments. In AHF-pEF, at comparable BNP and LV EF, hypertensive APE showed eccentric LV geometry but smaller RV and RA sizes, and higher RV systolic function, increased LV ventricular filling and systemic arterial loads. AHF resolution abolished the differences in PP/SV and LV diastolic load between APE and peHF whereas APE remained associated with more eccentric RV and higher TAPSE.

B-Type Natriuretic Peptide at Admission Is a Predictor of All-Cause Mortality at One Year after the First Acute Episode of New-Onset Heart Failure with Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) has been assessed extensively, but few studies analysed the predictive value of the NT-proBNP in patients with de novo and acute HFpEF. We sought to identify NT-proBNP at admission as a predictor for all-cause mortality and rehospitalisation at 12 months in patients with new-onset HFpEF. Methods: We analysed 91 patients (73 ± 11 years, 68% females) admitted for de novo and acute HFpEF, using the Cox proportional hazard risk model. Results: An admission NT-proBNP level above the threshold of 2910 pg/mL identified increased all-cause mortality at 12 months (AUC = 0.72, sensitivity = 92%, specificity = 53%, p < 0.001). All-cause mortality adjusted for age, gender, medical history, and medication in the augmented NT-proBNP group was 16-fold higher (p = 0.018), but with no difference in rehospitalisation rates (p = 0.391). The predictors of increased NT-proBNP ≥ 2910 pg/mL were: age (p = 0.016), estimated glomerular filtration rate (p = 0.006), left atrial volume index (p = 0.001), history of atrial fibrillation (p = 0.006), and TAPSE (p = 0.009). Conclusions: NT-proBNP above 2910 pg/mL at admission for de novo and acute HFpEF predicted a 16-fold increased mortality at 12 months, whereas values less than 2910 pg/mL forecast a high likelihood of survival (99.3%) in the next 12 months, and should be considered as a useful prognostic tool, in addition to its utility in diagnosing heart failure.

Minimal subphenotyping model for acute heart failure with preserved ejection fraction.

AimsApplication of the latent class analysis to acute heart failure with preserved ejection fraction (HFpEF) showed that the heterogeneous acute HFpEF patients can be classified into four distinct phenotypes with different clinical outcomes. This model‐based clustering required a total of 32 variables to be included. However, this large number of variables will impair the clinical application of this classification algorithm. This study aimed to identify the minimal number of variables for the development of optimal subphenotyping model.Methods and resultsThis study is a post hoc analysis of the PURSUIT‐HFpEF study (N = 1095), a prospective, multi‐referral centre, observational study of acute HFpEF [UMIN000021831]. We previously applied the latent class analysis to the PURSUIT‐HFpEF dataset and established the full 32‐variable model for subphenotyping. In this study, we used the Cohen's kappa statistic to investigate the minimal number of discriminatory variables needed to accurately classify the phenogroups in comparison with the full 32‐variable model. Cohen's kappa statistic of the top‐X number of discriminatory variables compared with the full 32‐variable derivation model showed that the models with ≥16 discriminatory variables showed kappa value of >0.8, suggesting that the minimal number of discriminatory variables for the optimal phenotyping model was 16. The 16‐variable model consists of C‐reactive protein, creatinine, gamma‐glutamyl transferase, brain natriuretic peptide, white blood cells, systolic blood pressure, fasting blood sugar, triglyceride, clinical scenario classification, infection‐triggered acute decompensated HF, estimated glomerular filtration rate, platelets, neutrophils, GWTG‐HF (Get With The Guidelines‐Heart Failure) risk score, chronic kidney disease, and CONUT (Controlling Nutritional Status) score. Characteristics and clinical outcomes of the four phenotypes subclassified by the minimal 16‐variable model were consistent with those by the full 32‐variable model. The four phenotypes were labelled based on their characteristics as ‘rhythm trouble’, ‘ventricular‐arterial uncoupling’, ‘low output and systemic congestion’, and ‘systemic failure’, respectively.ConclusionsThe phenotyping model with top 16 variables showed almost perfect agreement with the full 32‐variable model. The minimal model may enhance the future clinical application of this clustering algorithm.

Interrelation between heart failure with preserved ejection fraction and renal impairment

Heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD) are global diseases of increasing prevalence and are frequent co-diagnoses. The two conditions share common risk factors and CKD contributes to HFpEF development by a variety of mechanisms including systemic inflammation and myocardial fibrosis. HFpEF patients with CKD are generally older and have more advanced disease. CKD is a poor prognostic indicator in HFpEF, while the impact of HFpEF on CKD prognosis is not sufficiently investigated. Acute kidney injury (AKI) is common during admission with acute decompensated HFpEF, but short and long-term outcomes are not clear. Pharmacological treatment options for HFpEF are currently minimal, and even more so limited in the presence of CKD with hyperkalaemia being one of the main concerns encountered in clinical practice. Recent data on the role of sodium-glucose cotransporter 2 (SGLT2) inhibitors in the management of HFpEF are encouraging, especially in light of the abundance of evidence supporting improved renal outcomes. Herein, we review the pathophysiological links between HFpEF and CKD, the clinical picture of dual diagnosis, as well as concerns with regards to renal impairment in the context of HFpEF management.

Phenotyping of acute decompensated heart failure with preserved ejection fraction

ObjectiveThe pathophysiological heterogeneity of heart failure with preserved ejection fraction (HFpEF) makes the conventional ‘one-size-fits-all’ treatment approach difficult. We aimed to develop a stratification methodology to identify distinct subphenotypes of...

Predictors of thirty-day readmission in nonagenarians presenting with acute heart failure with preserved ejection fraction: a nationwide analysis.

BACKGROUDAcute heart failure with preserved ejection fraction (HFpEF) is a common but poorly studied cause of hospital admissions among nonagenarians. This study aimed to evaluate predictors of thirty-day readmission, in-hospital mortality, length of stay, and hospital charges in nonagenarians hospitalized with acute HFpEF.METHODSPatients hospitalized between January 2016 and December 2018 with a primary diagnosis of diastolic heart failure were identified using ICD-10 within the Nationwide Readmission Database. We excluded patients who died in index admission, and discharged in December each year to allow thirty-day follow-up. Univariate regression was performed on each variable. Variables with P-value < 0.2 were included in the multivariate regression model. RESULTSFrom a total of 45,393 index admissions, 43,646 patients (96.2%) survived to discharge. A total of 7,437 patients (15.6%) had a thirty-day readmission. Mean cost of readmission was 43,265 United States dollars (USD) per patient. Significant predictors of thirty-day readmission were chronic kidney disease stage III or higher [adjusted odds ratio (aOR) = 1.20, 95% CI: 1.07−1.34,P = 0.002] and diabetes mellitus (aOR = 1.18, 95% CI: 1.07−1.29,P = 0.001). Meanwhile, female (aOR = 0.90, 95% CI: 0.82−0.99,P = 0.028) and palliative care encounter (aOR = 0.27, 95% CI: 0.21−0.34,P < 0.001) were associated with lower odds of readmission. Cardiac arrhythmia (aOR = 1.46, 95% CI: 1.11−1.93, P = 0.007) and aortic stenosis (aOR = 1.36, 95% CI: 1.05−1.76,P = 0.020) were amongst predictors of in-hospital mortality. CONCLUSIONSIn nonagenarians hospitalized with acute HFpEF, thirty-day readmission is common and costly. Chronic comorbidities predict poor outcomes. Further strategies need to be developed to improve the quality of care and prevent the poor outcome in nonagenarians.

Prognostic Value of Multiple Circulating Biomarkers for 2-Year Death in Acute Heart Failure With Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a major global public health burden and lacks effective risk stratification. We aimed to assess a multi-biomarker model in improving risk prediction in HFpEF.Methods: We analyzed 18 biomarkers from the main pathophysiological domains of HF in 380 patients hospitalized for HFpEF from a prospective cohort. The association between these biomarkers and 2-year risk of all-cause death was assessed by Cox proportional hazards model. Support vector machine (SVM), a supervised machine learning method, was used to develop a prediction model of 2-year all-cause and cardiovascular death using a combination of 18 biomarkers and clinical indicators. The improvement of this model was evaluated by c-statistics, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).Results: The median age of patients was 71-years, and 50.5% were female. Multiple biomarkers independently predicted the 2-year risk of death in Cox regression model, including N-terminal pro B-type brain-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-TnT), growth differentiation factor-15 (GDF-15), tumor necrosis factor-α (TNFα), endoglin, and 3 biomarkers of extracellular matrix turnover [tissue inhibitor of metalloproteinases (TIMP)-1, matrix metalloproteinase (MMP)-2, and MMP-9) (FDR < 0.05). The SVM model effectively predicted the 2-year risk of all-cause death in patients with acute HFpEF in training set (AUC 0.834, 95% CI: 0.771–0.895) and validation set (AUC 0.798, 95% CI: 0.719–0.877). The NRI and IDI indicated that the SVM model significantly improved patient classification compared to the reference model in both sets (p < 0.05).Conclusions: Multiple circulating biomarkers coupled with an appropriate machine-learning method could effectively predict the risk of long-term mortality in patients with acute HFpEF. It is a promising strategy for improving risk stratification in HFpEF.