Chronic Heart Failure Risk Score Research Articles

Proteomic Correlates and Prognostic Significance of Kidney Injury in Heart Failure With Preserved Ejection Fraction.

Kidney disease is common in heart failure with preserved ejection fraction (HFpEF). However, the biologic correlates and prognostic significance of kidney injury (KI), in HFpEF, beyond the estimated glomerular filtration rate (eGFR), are unclear. Using baseline plasma samples from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, we measured the following KI biomarkers: cystatin-C, fatty acid-binding protein-3, Beta-2 microglobulin, neutrophil gelatinase-associated lipocalin, and kidney-injury molecule-1. Factor analysis was used to extract the common variability underlying these biomarkers. We assessed the relationship between the KI-factor score and the risk of death or HF-related hospital admission in models adjusted for the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. We also assessed the relationship between the KI factor score and ~5000 plasma proteins, followed by pathway analysis. We validated our findings among HFpEF participants in the Penn Heart Failure Study. KI was associated with the risk of death or HF-related hospital admission independent of the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. Both the risk score and eGFR were no longer associated with death or HF-related hospital admission after adjusting for the KI factor score. KI was predominantly associated with proteins and biologic pathways related to complement activation, inflammation, fibrosis, and cholesterol homeostasis. KI was associated with 140 proteins, which reproduced across cohorts. Findings regarding biologic associations and the prognostic significance of KI were also reproduced in the validation cohort. KI is associated with adverse outcomes in HFpEF independent of baseline eGFR. Patients with HFpEF and KI exhibit a plasma proteomic signature indicative of complement activation, inflammation, fibrosis, and impaired cholesterol homeostasis.

Abstract 13344: Differential Impact of Self-Care Behaviour on Mortality Between Patients With Stable and Recent Worsening Chronic Heart Failure

Backgrounds: Although self-care is crucial to maintain health and recommended in the guidelines in patients with chronic heart failure (CHF), its prognostic significance is controversial. We hypothesized that self-care is more effective in vulnerable patients with recent hospitalization due to worsening HF (WHF). The aim of this study was to investigate the prognostic significance of self-care behaviour on mortality between patients with stable and recent worsening CHF. Methods: We prospectively examined consecutive 1,873 CHF patients from a Japanese multicenter registry and assessed the European Heart Failure Self-care Behaviour Scale (EHFScBS) at enrollment. The patients were divided into inpatient due to WHF (WHF group) and outpatient stable CHF (stable CHF group). The optimal EHFScBS was defined as more than 70 based on previous reports. The primary outcome was all-cause death. Results: Of studied patients (1,102 male, mean age 72 ± 13 years), 625 (33%) and 1,165 (67%) were classified into WHF and stable CHF groups, respectively. During a median follow-up period of 427 (IQR 273 - 642) days, the primary outcome occurred in 50 patients. In stable CHF group, there was no significant difference on primary outcome between optimal and suboptimal EHFScBS (P = 0.65) (Figure A). On the other hand, patients with suboptimal EHFScBS showed a higher incidence of death than those with optimal score in WHF group (P = 0.01) (Figure B). In WHF group, Cox regressions showed that the EHFScBS score was independently associated with mortality (HR 0.51, 95% CI 0.26-0.99) adjusted for significant covariates including hemoglobin, estimated glomerular filtration rate, serum sodium, log NT-proBNP, and the Meta-Analysis Global Group in Chronic Heart Failure risk score. Conclusions: In patients with recent worsening, not stable CHF, the EHFScBS was associated with subsequent mortality, indicating that the self-care education might be more effective for patients with recent worsening CHF.

Baroreflex activation therapy in patients with heart failure with reduced ejection fraction: a single-centre experience.

Heart failure with reduced ejection fraction (HFrEF) is associated with excessive sympathetic and impaired parasympathetic activity. The Barostim Neo™ device is used for electronical baroreflex activation therapy (BAT) to counteract autonomic nervous system dysbalance. Randomized trials have shown that BAT improves walking distance and reduces N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels at least in patients with only moderate elevation at baseline. Its impact on the risk of heart failure hospitalization (HFH) and death is not yet established, and experience in clinical routine is limited. We report on patient characteristics and clinical outcome in a retrospective, non-randomized single-centre registry of BAT in HFrEF. Patients in the New York Heart Association (NYHA) Classes III and IV with a left ventricular ejection fraction (LVEF) <35% despite guideline-directed medical therapy were eligible. Symptom burden, echocardiography, and laboratory testing were assessed at baseline and after 12months. Clinical events of HFH and death were recorded at routine clinical follow-up. Data are shown as number (%) or median (inter-quartile range). Between 2014 and 2020, 30 patients were treated with BAT. Median age was 67 (63-77) years, and 27 patients (90%) were male. Most patients (83%) had previous HFH. Device implantation was successful in all patients. At 12months, six patients had died and three were alive but did not attend follow-up. NYHA class was III/IV in 26 (87%)/4 (13%) patients at baseline, improved in 19 patients, and remained unchanged in 5 patients (P<0.001). LVEF improved from 25.5 (20.0-30.5) % at baseline to 30.0 (25.0-36.0) % at 12months (P=0.014). Left ventricular end-diastolic diameter remained unchanged. A numerical decrease in NT-proBNP [3165 (880-8085) vs. 1001 (599-3820) pg/mL] was not significant (P=0.526). Median follow-up for clinical events was 16 (10-33) months. Mortality at 1 (n=6, 20%) and 3years (n=10, 33%) was as expected by the Meta-Analysis Global Group in Chronic Heart Failure risk score. Despite BAT, event rate was high in patients with NYHA Class IV, NT-proBNP levels >1600pg/mL, or estimated glomerular filtration rate (eGFR) <30mL/min at baseline. NYHA class and eGFR were independent predictors of mortality. Patients with HFrEF who are selected for BAT are in a stage of worsening or even advanced heart failure. BAT appears to be safe and improves clinical symptoms and-to a modest degree-left ventricular function. The risk of death remains high in advanced disease stages. Patient selection seems to be crucial, and the impact of BAT in earlier disease stages needs to be established.

Novel Measures of Arterial Hemodynamics and Wave Reflections Associated With Clinical Outcomes in Patients With Heart Failure.

Background Arterial stiffness and earlier wave reflections can increase afterload and impair cardiovascular function. Most prior studies have been performed in patients with preserved left ventricular function. We describe novel measures of pulsatile arterial hemodynamics and their association with clinical outcomes in patients with heart failure with reduced ejection fraction. Methods and Results Participants with heart failure with reduced ejection fraction (n=137, median age 56 years, 49% women, 58% Black) and age-matched healthy controls (n=124) underwent measurements of large artery stiffness and pulsatile arterial hemodynamics. Carotid-femoral pulse wave velocity and augmentation index were assessed using radial applanation tonometry. Pressure-flow analyses derived reflected wave transit time, the systolic pressure-time integral imposed by proximal aortic characteristic impedance, and the pressure-time integral from wave reflection (wasted pressure effort). Cox proportional hazards models defined associations between hemodynamic measures and (1) all-cause death and (2) a combined end point of left ventricular assist device implant, heart transplant, and death, at 2 years adjusted for race, BNP (B-type natriuretic peptide), and the Meta-Analysis Global Group in Chronic Heart Failure Risk Score. Compared with controls, participants with heart failure with reduced ejection fraction exhibited similar carotid-femoral pulse wave velocity (6.8±1.6 versus 7.0±1.6 m/s, P=0.40) but higher augmentation index normalized to a heart rate of 75 bpm (13±2% versus 22±2%, P<0.001). Shorter reflected wave transit time (ie, earlier wave reflection arrival to the proximal aorta) was associated with an increased risk of death (adjusted hazard ratio [aHR] 1.67 [95% CI 1.03-1.63]) and the combined end point of death/left ventricular assist device/heart transplant (aHR, 1.61 [95% CI, 1.06-2.44]) at 2 years. Wasted pressure effort/proximal aortic characteristic impedance, representing the proportion of systolic load from wave reflection versus aortic root characteristic impedance, was univariately associated with death (hazard ratio (HR), 1.44 [95% CI, 1.05-1.97]) and with death/left ventricular assist device/heart transplant on univariate (HR, 1.42 [95% CI, 1.07-1.88]) and multivariable (aHR, 1.40 [95% CI, 1.02-1.93]) analysis. Conclusions Increased left ventricular systolic load from premature wave reflections is associated with adverse clinical outcomes in patients with heart failure with reduced ejection fraction.

Validation of the Meta-Analysis Global Group in Chronic Heart Failure risk score for the prediction of 1-year mortality in a Chinese cohort.

The Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score was developed in 2013 to predict survival in heart failure (HF) patients. However, it has yet to be validated in a Chinese population. Our study aimed to investigate the ability of the score to predict 1-year mortality in a Chinese population. Consecutive patients with HF were retrospectively selected from the inpatient electronic medical records of the cardiology department in a regional hospital in China. A total integer score was calculated for each enrolled patient based on the value of each risk factor in the MAGGIC scoring system. Each enrolled patient was followed for at least 1 year. The observational endpoint of this study was all-cause mortality. The predictive ability of the MAGGIC score was assessed by comparing observed and predicted mortality within 1 year. Between January 2018 and December 2020, a total of 635 patients were included in the study: 57 (9.0%) of whom died within 1 year after discharge. The average age of all patients was 74.6 ± 11.2 years, 264 of them (41.6%) were male, and the average left ventricular ejection fraction was 50.7% ± 13.2%. The area under the receiver operating characteristic curve was 0.840 (95% confidence interval: 0.779, 0.901), which indicated a fair discriminatory ability of the score. The Hosmer-Lemeshow test result ( χ2 = 12.902, degree of freedom = 8, P = 0.115) indicated that the MAGGIC score had good calibration. The decision curve analysis showed that the MAGGIC score yielded a good clinical net benefit and net reduction in interventions. This validation of the MAGGIC score showed that it has a good ability to predict 1-year mortality in Chinese patients with HF after discharge. Due to regional and inter-hospital differences, external validation studies need to be further confirmed in other centers.

Abstract 11803: Applicability of the New Proposed Criteria for Iron Deficiency in Japanese Patients With Heart Failure

Backgrounds: Iron deficiency (ID) is a common comorbidity in patients with heart failure (HF). A recent study from a large single-center chronic HF cohort including predominantly white British population showed that ID defined by current guideline criteria was not associated with poor outcome, and a new ID criteria targeting for HF population was proposed. However, its external applicability is unclear. Methods: We prospectively examined consecutive 711 chronic HF patients and measured serum iron, transferrin saturation (TSAT) and serum ferritin from a Japanese multicenter registry. The proposed ID criteria were TSAT &lt;20% and serum iron ≤13 mmol/L and the guideline ID criteria were serum ferritin &lt;100 ng/mL or, when ferritin was 100-299 ng/mL, TSAT &lt;20%. The primary outcome was all-cause death. Results: Of studied patients (433 male, mean age 71 ± 13 years, mean left ventricular ejection fraction 47 ± 16%), 198 (28%) and 416 (59%) met the proposed and guideline ID criteria, respectively. During a median follow-up period of 441 (IQR 306-564) days, the primary outcome occurred in 50 patients. There was no significant difference on primary outcome between the patients with and without guideline ID criteria ( P = 0.24) ( Figure A ), while patients with serum iron ≤10 mmol/L showed a higher mortality than those without ( P = 0.004) ( Figure B ). In multivariable Cox regressions, the proposed ID criteria, but not guideline ID criteria, were independently associated with higher mortality (HR 1.92, 95% CI 1.06-3.47; and HR 1.42; 95% CI 0.79-1.24, respectively) adjusted for significant covariates including age, hemoglobin, estimated glomerular filtration rate and log NT-proBNP, and the Meta-Analysis Global Group in Chronic Heart Failure risk score. Conclusions: As defined by the proposed criteria, but not the guideline criteria, ID was associated with higher mortality in patients with chronic HF, suggesting that the proposed ID criteria might be applicable to Japanese population.

Should HFrEF patients with NYHA class II expect benefit from CCM therapy? Results from the MAINTAINED observational study.

Cardiac contractility modulation (CCM) is an FDA-approved device therapy for patients with refractory systolic heart failure and normal QRS width. Randomized trials demonstrated benefits of CCM primarily for patients with severe heart failure (> NYHA class II). To better understand individualized indication in clinical practice, we compared the effect of CCM in patients with baseline NYHA class II vs. NYHA classIII or ambulatory IV over the 5-year period in our large clinical registry (MAINTAINED Observational Study). Changes in NYHA class, left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), NT-proBNP level, and KDIGO chronic kidney diseasestage were compared as functional parameters. In addition, mortality within 3years was compared with the prediction of the Meta-Analysis Global Group in Chronic heart failure risk score. A total of 172 patients were included in the analyses (10% with NYHA class II). Only patients with NYHA class III/IV showed a significant improvement in NYHA class over 5years of CCM (II: 0.1 ± 0.6; p = 0.96 vs. III/IV: -0.6 ± 0.6; p < 0.0001). In both groups, LVEF improved significantly (II: 4.7 ± 8.3; p = 0.0072 vs. III/IV: 7.0 ± 10.7%; p < 0.0001), while TAPSE improved significantly only in NYHA class III/IV patients (II: 2.2 ± 1.6; p = 0.20 vs. III/IV: 1.8 ± 5.2mm; p = 0.0397). LVEF improvement was comparable in both groups over 5years of CCM (p = 0.83). NYHA class II patients had significantly lower NT-proBNP levels at baseline (858 [175/6887] vs. 2632 [17/28830] ng/L; p = 0.0044), which was offset under therapy (399 [323/1497] vs. 901 [13/18155] ng/L; p = 0.61). Actual 3-year mortality was 17 and 26% vs. a predicted mortality of 31 and 42%, respectively (p = 0.0038 for NYHAclass III/IVpatients). NYHA classIII/IV patients experienced more direct and extensive functional improvements with CCM and a survival benefit compared with the predicted risk. However, our data suggest that NYHA classII patients may also benefit from the sustained positive effects of LVEF improvement.

Vericiguat and NT-proBNP in patients with heart failure with reduced ejection fraction: analyses from the VICTORIA trial.

Treatment response to vericiguat, based on baseline N-terminal pro-brain natriuretic peptide (NT-proBNP) subgroups specified in the protocol, was evaluated in the heart failure (HF) VICTORIA trial population by post hoc analysis of combined lower three quartiles [Q1-Q3] vs. the upper quartile [Q4]. VICTORIA participants with available baseline NT-proBNP levels (n=4805; 95.1% of total) were included. Compared with patients in Q1-Q3 (NT-proBNP: Q1, ≤1556pg/mL; Q2, >1556-2816pg/mL; and Q3, >2816-5314pg/mL), patients in Q4 (NT-proBNP: >5314pg/mL) were older (69.2±12.0 vs. 66.6±12.1years), had lower mean ejection fraction (27.2±8.3% vs. 29.5±8.2%; P<0.0001), and were more likely to be in New York Heart Association (NYHA) Class III (51.8 vs. 35.6%) or IV (2.4 vs. 1.0%). Compared with Q1-Q3, patients in Q4 had higher mean Meta-Analysis Global Group in Chronic Heart Failure risk score (27.3±6.6 vs. 23.5±6.4; P<0.0001), had lower mean estimated glomerular filtration rate (eGFR; 51.5±25.5 vs. 65.0±26.8mL/min/1.73m2 ; P<0.0001) and haemoglobin (12.8±2.0 vs. 13.6±1.9g/dL; P<0.0001), and more had atrial fibrillation (48.7% vs. 43.1%; P=0.0007) and were randomized while hospitalized for HF (14.8 vs. 9.9%; P<0.0001). Target dose was achieved in 72.3 and 63.7% of patients in Q1-Q3 and Q4, respectively (P<0.0001). Primary outcome (composite of time to cardiovascular death or first HF hospitalization) rates were 24.5 and 31.7 per 100 patient-years for vericiguat and placebo in Q1-Q3 [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.69-0.88, P<0.001] and 73.6 and 63.6 in Q4 (HR 1.15; 95% CI 0.99-1.34, P=0.070). Serious adverse events were more frequent in NT-proBNP Q4 (total population) compared with Q1-Q3 (38.3 vs. 32.3%; P=0.0001), driven mainly by the placebo group. Adverse events leading to death were more frequent in Q4 than Q1-Q3 (5.8 vs. 2.4%; P<0.0001). Plasma NT-proBNP may help identify patients with worsening HF with reduced ejection fraction, in whom the beneficial effects of vericiguat may be highest. Patients with highest NT-proBNP values are probably too far advanced, suffering more co-morbidities, or still clinically unstable after decompensation to derive benefit from vericiguat.

Association of peripheral venous pressure with adverse post-discharge outcomes in patients with acute heart failure: a prospective cohort study.

Congestion is the major cause of hospitalization for heart failure (HF). Traditional bedside assessment of congestion is limited by insufficient accuracy. Peripheral venous pressure (PVP) has recently been shown to accurately predict central venous congestion. We examined the association between PVP before discharge and post-discharge outcomes in hospitalized patients with acute HF. Bedside PVP measurement at the forearm vein and traditional clinical examination were performed in 239 patients. The association with the primary composite endpoint of cardiovascular death or HF hospitalization and the incremental prognostic value beyond the established HF risk score was examined. The PVP correlated with peripheral oedema, jugular venous pressure, and inferior vena cava diameter, but not with brain-type natriuretic peptide. The 1-year incidence of the primary outcome measure in the first, second, and third tertiles of PVP was 21.4, 29.9, and 40.7%, respectively (log-rank P = 0.017). The adjusted hazard ratio of PVP per 1 mmHg increase for the 1-year outcome was 1.08 [95% confidence interval (1.03-1.14), P = 0.004]. When added onto the Meta-Analysis Global Group in Chronic HF risk score, PVP significantly increased the area under the receiver-operating characteristic curve for predicting the outcome [from 0.63 (0.56-0.71) to 0.70 (0.62-0.77), P = 0.02), while traditional assessments did not. The addition of PVP also yielded significant net reclassification improvement [0.46 (0.19-0.74), P < 0.001]. The PVP at discharge correlated with prognosis. The results warrant further investigation to evaluate the clinical application of PVP measurement in the care of HF. UMIN000034279.

Participation in a Heart Failure Clinical Trial: Perspectives and Opportunities From the VICTORIA Trial and VICTORIA Simultaneous Registry.

Randomized controlled trials (RCTs) often target enrollment of patients with demographics and outcomes less representative of the broader population of interest. To provide context for the VICTORIA trial (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction), we designed a registry of hospitalized patients with worsening heart failure to characterize their clinical profile, outcomes, and reasons for their nonparticipation in a RCT. Fifty-one RCT sites in Canada and the United States participated. Eligible patients included those with chronic heart failure, hospitalized for heart failure, and an ejection fraction <45%; no other exclusions were applied. Sites identified patients between 2017 and 2019 during the RCT enrollment period. RCT eligibility criteria were applied, and non-mutually exclusive reasons for nonenrollment were captured. Mortality at 1 year was estimated via the Meta-Analysis Global Group in Chronic Heart Failure risk score or as observed in the RCT. Overall, 2056 patients were enrolled in the registry; 61% (n=1256) were ineligible for the RCT, 37% (n=766) were eligible but not enrolled, and 2% (n=34) were also enrolled in the RCT. Registry participants had a median age of 70, 33% were women, and 63% were White. The median risk score predicted a 20.9% 1-year mortality, higher than in the RCT (predicted 14.7% and observed 11.5%). Major reasons for ineligibility in the RCT included the use of nitrates (23%), systolic blood pressure <100 mm Hg (12%), and substance use (11%) with other exclusion criteria <10%. For eligible patients, reasons for nonparticipation in the RCT included lack of interest in participating (28%), poor compliance (25%), inability to complete follow-up (23%), too sick (20%), unable to provide consent (17%), and distance from site (15%). Patients with worsening heart failure in routine clinical practice exhibit high-risk features, and approximately one-third were eligible for an RCT but excluded. The majority of these nonparticipating patients had modifiable reasons. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02861534.

Cardiac and Noncardiac Disease Burden and Treatment Effect of Sacubitril/Valsartan: Insights From a Combined PARAGON-HF and PARADIGM-HF Analysis.

The net clinical benefit of cardiac disease-modifying drugs might be influenced by the interaction of different domains of disease burden. We assessed the relative contribution of cardiac, comorbid, and demographic factors in heart failure (HF) and how their interplay might influence HF prognosis and efficacy of sacubitril/valsartan across the spectrum of left ventricular ejection fraction. We combined data from 2 global trials that evaluated the efficacy of sacubitril/valsartan compared with a renin-angiotensin antagonist in symptomatic HF patients (PARADIGM-HF [Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure; n=8399] and PARAGON-HF [Prospective Comparison of Angiotensin-Converting Enzyme Inhibitor With Angiotensin Receptors Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction; n=4796]). We decomposed the previously validated Meta-Analysis Global Group in Chronic Heart Failure risk score into cardiac (left ventricular ejection fraction, New York Heart Association class, blood pressure, time since HF diagnosis, HF medications), noncardiac comorbid (body mass index, creatinine, diabetes, chronic obstructive pulmonary disease, smoking), and demographic (age, gender) categories. Based on these domains, an index representing the balance of cardiac to noncardiac comorbid burden was created (cardiac-comorbid index). Clinical outcomes were time to first HF hospitalization or cardiovascular deaths and all-cause mortality. Higher scores of the cardiac domain were observed in PARADIGM-HF (10 [7-13] versus 5 [3-6], P<0.001) and higher scores of the demographic domain in PARAGON-HF (10 [8-13] versus 5 [2-9], P<0.001). In PARADIGM-HF, the contribution of the cardiac domain to clinical outcomes was greater than the noncardiac domain (P<0.001), while in PARAGON-HF the attributable risk of the comorbid and demographic categories predominated. Individual scores from each sub-domain were linearly associated with the risk of clinical outcomes (P<0.001). Beneficial effects of sacubitril/valsartan were observed in patients with preponderance of cardiac over noncardiac comorbid burden (cardiac-comorbid index >5 points), suggesting a significant treatment effect modification (interaction P<0.05 for both outcomes). Domains of disease burden are clinically relevant features that influence the prognosis and treatment of patients with HF. The therapeutic benefits of sacubitril/valsartan vary according to the balance of components of disease burden, across different ranges of left ventricular ejection fraction.

Comparison of left ventricular longitudinal systolic function parameters in the prediction of adverse outcome in heart failure with preserved ejection fraction

AimsSeveral different diagnostic parameters can be used to assess left ventricular (LV) longitudinal systolic function, but no studies comparing their predictive value have been conducted. We sought to compare the prognostic value of LV long‐axis function parameters at rest and exercise using the population with heart failure with preserved ejection fraction (HFpEF).Methods and resultsClinical and biochemical variables were collected at baseline in 201 patients with HFpEF. Echocardiography was performed at rest and immediately after exercise, with measurement of mitral annular plane systolic excursion, systolic tissue velocity (s′), global longitudinal strain (GLS), and global longitudinal strain rate (GLSR). Participants were followed for 48 (24–60) months for heart failure hospitalization and cardiovascular death. Seventy‐four patients (36.8%) met the study endpoint. Cox regression analysis revealed that after adjustment for Meta‐Analysis Global Group in Chronic Heart Failure risk score, brain natriuretic peptide (BNP), and peak VO2, heart failure hospitalization and cardiovascular death were significantly associated with GLS at rest [hazard ratio (HR) 0.91; 95% confidence interval (CI) 0.84–0.98; P = 0.016], GLS after exercise (HR 0.84; 95% CI 0.77–0.91; P < 0.001), and GLSR after exercise (HR 0.13; 95% CI 0.04–0.48; P = 0.002). The addition of each of the following: exercise GLS and GLSR and resting GLS to the base model including Meta‐Analysis Global Group in Chronic Heart Failure, BNP, and peak VO2 improved predictive power for the study endpoint [net reclassification improvement (NRI) = 49%, P < 0.001; NRI = 42%, P = 0.004; and NRI = 38%, P = 0.009, respectively]. Exercise GLS was the only longitudinal parameter significantly improving c‐statistics of the base model (0.68 vs. 0.73; P = 0.047).ConclusionsEchocardiographic parameters of LV longitudinal function are not equipotential in predicting adverse outcomes in HFpEF. LV deformation indices, especially assessed with exercise, show the highest predictive utility independent from and incremental to clinical data and BNP.

Prognostic Value of Pulmonary Transit Time by Cardiac Magnetic Resonance on Mortality and Heart Failure Hospitalization in Patients With Advanced Heart Failure and Reduced Ejection Fraction.

Pulmonary transit time (PTT) from first-pass perfusion imaging is a novel parameter to evaluate hemodynamic congestion by cardiac magnetic resonance (cMR). We sought to evaluate the additional prognostic value of PTT in heart failure with reduced ejection fraction over other well-validated predictors of risk including the Meta-Analysis Global Group in Chronic Heart Failure risk score and ischemic cause. We prospectively followed 410 patients with chronic heart failure with reduced ejection fraction (61±13 years, left ventricular (LV) ejection fraction 24±7%) who underwent a clinical cMR to assess the prognostic value of PTT for a primary endpoint of overall mortality and secondary composite endpoint of cardiovascular death and heart failure hospitalization. Normal reference values of PTT were evaluated in a population of 40 asymptomatic volunteers free of cardiovascular disease. Results PTT was significantly increased in patients with heart failure with reduced ejection fraction as compared to controls (9±6 beats and 7±2 beats, respectively, P<0.001), and correlated not only with New York Heart Association class, cMR-LV and cMR-right ventricular (RV) volumes, cMR-RV and cMR-LV ejection fraction, and feature tracking global longitudinal strain, but also with cardiac output. Over 6-year median follow-up, 182 patients died and 200 reached the secondary endpoint. By multivariate Cox analysis, PTT was an independent and significant predictor of both endpoints after adjustment for Meta-Analysis Global Group in Chronic Heart Failure risk score and ischemic cause. Importantly in multivariable analysis, PTT in beats had significantly higher additional prognostic value to predict not only overall mortality (χ2 to improve, 12.3; hazard ratio, 1.35 [95% CI, 1.16-1.58]; P<0.001) but also the secondary composite endpoints (χ2 to improve=20.1; hazard ratio, 1.23 [95% CI, 1.21-1.60]; P<0.001) than cMR-LV ejection fraction, cMR-RV ejection fraction, LV-feature tracking global longitudinal strain, or RV-feature tracking global longitudinal strain. Importantly, PTT was independent and complementary to both pulmonary artery pressure and reduced RV ejection fraction<42% to predict overall mortality and secondary combined endpoints. Despite limitations in temporal resolution, PTT derived from first-pass perfusion imaging provides higher and independent prognostic information in heart failure with reduced ejection fraction than clinical and other cMR parameters, including LV and RV ejection fraction or feature tracking global longitudinal strain. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03969394.

Multimarker approach including CRP, sST2 and GDF-15 for prognostic stratification in stable heart failure.

AimsInflammation and cardiac remodelling are common and synergistic pathways in heart failure (HF). Emerging biomarkers such as soluble suppression of tumorigenicity 2 (sST2) and growth differentiation factor‐15 (GDF‐15), which are linked to inflammation and fibrosis process, have been proposed as prognosis factors. However, their potential additive values remain poorly investigated.Methods and resultsHere, we aimed at evaluating inflammatory and remodelling biomarkers to predict both short‐term and long‐term mortality in a population with chronic HF in comparison with other classical clinical or biological markers (i.e. N terminal pro brain natriuretic peptide, hs‐cTnT, C‐reactive protein) alone or using meta‐analysis global group in chronic HF risk score in a cohort of 182 patients followed during 80 months (interquartile range: 12.3–90.0). Proportional hazard assumption does not hold for sST2 and C‐reactive protein, and follow‐up was split into short term (less than 1 year), midterm (between 1 and 5 years), and long term (after 5 years). In univariate analysis, C‐reactive protein and sST2 were predictive of short‐term mortality but not of middle term and long term whereas GDF‐15 was predictive of short and mid‐term but not of long‐term mortality. In a multivariate model after adjustment for meta‐analysis global group in chronic HF score including the three markers, only sST2 was predictive of short‐term mortality (P = 0.0225), and only GDF‐15 was predictive of middle term mortality (P = 0.0375). None of the markers was predictive of long‐term mortality.ConclusionsOur results demonstrate that both sST2 and GDF‐15 significantly improve the prognosis evaluation of HF patients and suggest that the value of GDF‐15 is more sustained overtime and could predict middle term events.

Clinimetric analysis of heart failure in Mexican patients.

Heart failure (HF) is a syndrome characterized basically by a circulatory deficit to cover the metabolic and energetic demands of the body. This condition has a broad spectrum in its clinical presentation, affects the quality of life significantly, impacts the family/social environment, and generates a great demand for health services. The purpose of this research is to report the situational diagnose of patients with HF in Mexico. We evaluated 292 patients, 70.2% were men. Average age was 56.7 ± 14.3 years. Ischemic heart disease is the main etiology (98 patients, 33.9%) followed by hypertensive (22.6%) and idiopathic (23.3%) heart disease. The associated clinical background was obesity (31.1%), systemic hypertension (36.7%), myocardial infarction (26.4%), and dyslipidemia (15.1%). The most common symptom was stress dyspnea (41.4%) and jugular vein engorgement at physical examination (32.5%). Anemia was observed in 1% of patients. The average left ventricular ejection fraction was 29.2 ± 10.6%. Sinus rhythm was the most frequently detected in 84.9%. 19.9% of patients had an implantable cardioverter-defibrillator or cardiac resynchronization therapy. 13.7% of patients with QRS > 130 ms. In our population, the meta-analysis global group in chronic heart failure risk score calculated was 16.8 ± 5.7 and for EMPHASIS 3.3 ± 1.5. We observed that age at presentation in HF in this analysis is at least 10 years younger than in other reports. The grade of obesity takes relevance in our group. The association of anemia and HF in Mexico is rare.

Multiple Plasma Biomarkers for Risk Stratification in Patients With Heart Failure and Preserved Ejection Fraction

BackgroundBetter risk stratification strategies are needed to enhance clinical care and trial design in heart failure with preserved ejection fraction (HFpEF). ObjectivesThe purpose of this study was to assess the value of a targeted plasma multi-marker approach to enhance our phenotypic characterization and risk prediction in HFpEF. MethodsIn this study, the authors measured 49 plasma biomarkers from TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial participants (n = 379) using a Multiplex assay. The relationship between biomarkers and the risk of all-cause death or heart failure-related hospital admission (DHFA) was assessed. A tree-based pipeline optimizer platform was used to generate a multimarker predictive model for DHFA. We validated the model in an independent cohort of HFpEF patients enrolled in the PHFS (Penn Heart Failure Study) (n = 156). ResultsTwo large, tightly related dominant biomarker clusters were found, which included biomarkers of fibrosis/tissue remodeling, inflammation, renal injury/dysfunction, and liver fibrosis. Other clusters were composed of neurohormonal regulators of mineral metabolism, intermediary metabolism, and biomarkers of myocardial injury. Multiple biomarkers predicted incident DHFA, including 2 biomarkers related to mineral metabolism/calcification (fibroblast growth factor-23 and OPG [osteoprotegerin]), 3 inflammatory biomarkers (tumor necrosis factor-alpha, sTNFRI [soluble tumor necrosis factor-receptor I], and interleukin-6), YKL-40 (related to liver injury and inflammation), 2 biomarkers related to intermediary metabolism and adipocyte biology (fatty acid binding protein-4 and growth differentiation factor-15), angiopoietin-2 (related to angiogenesis), matrix metalloproteinase-7 (related to extracellular matrix turnover), ST-2, and N-terminal pro–B-type natriuretic peptide. A machine-learning–derived model using a combination of biomarkers was strongly predictive of the risk of DHFA (standardized hazard ratio: 2.85; 95% confidence interval: 2.03 to 4.02; p < 0.0001) and markedly improved the risk prediction when added to the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure Risk Score) risk score. In an independent cohort (PHFS), the model strongly predicted the risk of DHFA (standardized hazard ratio: 2.74; 95% confidence interval: 1.93 to 3.90; p < 0.0001), which was also independent of the MAGGIC risk score. ConclusionsVarious novel circulating biomarkers in key pathophysiological domains are predictive of outcomes in HFpEF, and a multimarker approach coupled with machine-learning represents a promising strategy for enhancing risk stratification in HFpEF.