Heart Failure Score Research Articles

Abstract 16139: A Targeted Proteomic Approach to Identify Circulating Biomarkers of Heart Failure Risk in Patients With Type 2 Diabetes Mellitus in DECLARE-TIMI 58

Background: Patients (pts) with type 2 diabetes mellitus (T2DM) are at increased risk of heart failure (HF); however, the underlying mechanisms by which T2DM contributes to HF are incompletely understood. Hypothesis: We aimed to identify biological pathways associated with risk of hospitalization for HF (HHF) in a well-characterized cohort with T2DM followed for a median of 4.2 yrs. Methods: DECLARE-TIMI 58 was a randomized trial of dapagliflozin in pts with T2DM. We performed a nested case-control study of 184 candidate biomarkers (Olink CV II and CV III) in pts hospitalized for HF (n=432) and controls matched on age, sex, prior HF, prior CV disease, and f/u time (n=432). We evaluated associations between baseline biomarkers and HHF using logistic regression with a stringent threshold for significance (Bonferroni). Biomarkers were ranked according to Wald χ 2 values. ORs for the top 10 biomarkers were further adjusted for the components of the TIMI Risk Score for HF in Diabetes (AF, UACR, eGFR, CAD). ORs are per 1-SD. Results: 45 biomarkers were significantly associated with HHF. The 10 strongest associations were seen with N-terminal pro-B type natriuretic peptide (NT-proBNP), B type natriuretic peptide (BNP), spondin-1 (SPON1), insulin-like growth factor-binding protein 7 (IGFBP7), interleukin-6 (IL-6), fibroblast growth factor-23 (FGF-23), transferrin receptor protein 1 (TR), metalloproteinase inhibitor 4 (TIMP4), matrix metalloproteinase-2 (MMP-2), C-X-C motif chemokine 16 (CXCL16) ( Fig ). All 10 biomarkers were significantly associated with HHF both in pts with and without a history of HF. These proteins represent pathobiological axes implicated in hemodynamic stress, inflammation, myocardial hypertrophy, and cellular senescence, among others. Conclusions: A targeted proteomic approach identified established (NT-proBNP, BNP), investigational (IGFBP7, FGF-23, IL-6, TR, TIMP4, MMP-2, CXCL16), and novel (SPON1) biomarkers of HHF in pts with T2DM.

Effects of the Cardiac and Comorbid Conditions Heart Failure (3C-HF) Score at Admission on Life Space at Three Months after Hospital Discharge in Elderly Patients with Heart Failure: A Short Report.

We assessed 22 elderly patients with heart failure, 3 months after hospital discharge. We examined and compared factors that predict small life space after discharge with the same factors before discharge. Life-Space Assessment was used to classify the participants as either having “small living spaces” or “large living spaces”. We collected data regarding characteristics, Cardiac and Comorbid Conditions Heart Failure Score (3C-HF score), and evaluated motor function. We also collected data on the patients’ lifestyle habits. We investigated spreading life space at 3 months after discharge by mailing a questionnaire to the subjects. Using multiple logistic regression analysis, we were able to predict the patients having a small life space at 3 months after discharge by the Cardiac and Comorbid Conditions Heart Failure (3C-HF) score (odds ratio, 1.19; 95% confidence interval, 1.01–1.39; p = 0.038) at admission. Overall, the 3C-HF score at admission may be associated with the size of life space at 3 months after hospital discharge in elderly patients with heart failure. Future multicenter studies should be conducted to validate the results of this study by measuring post-discharge activity with a more objective index.

Structural and functional reverse myocardial remodeling following transcatheter aortic valve replacement

Abstract Background Myocardial reverse remodeling determines outcome in patients with severe aortic stenosis (AS) following transcatheter aortic valve replacement (TAVR). However, little is known about the interplay of myocardial function and structure after TAVR. Since cardiac magnetic resonance (CMR) imaging allows comprehensive quantification of both structure and function we aimed to assess changes in myocardial tissue composition and deformation before and following TAVR. Methods CMR imaging was performed in 40 prospectively enrolled patients with severe AS before and one year after TAVR. Myocardial function was characterized using volumetry and CMR-feature-tracking (FT) deformation imaging of left ventricular (LV) global longitudinal strain (GLS) and atrial function (atrial reservoir ES, conduit Ee and booster pump strain EA). Myocardial structure was assessed using T1 mapping and late gadolinium enhancement (LGE) analysis. LV cellular and matrix volumes were calculated based on extra cellular volume fraction (ECV) and LV mass. CMR-FT results were compared to a control group of twenty patients with normal biventricular function. Moreover, biomarkers (NT-proBNP), functional (six-minute-walking-test) and clinical status (NYHA, Minnesota LIVING WITH HEART FAILURE score) were determined at baseline and one-year follow-up. Results Regression of both cellular (−20.6%, p<0.001) and matrix volumes (−12.3%, p=0.003) and subsequently increased ECV (+9.0%, p=0.001) were documented one year after TAVR. Ventricular and atrial strains were impaired at baseline (GLS p=0.004, Es p<0.001, Ee p<0.001) and recovered during follow-up (GLS p<0.001, Es p=0.005, Ee p=0.001). These changes were paralleled by improvements in NYHA (p<0.001) and Minnesota (p<0.001) scores as well as decline in NT-proBNP levels (p=0.001). There was a significant association of LV fibrosis as defined by matrix volume and extent of LGE and ventricular and atrial functional impairment (correlation of matrix volume and: GLS r=0.57, p<0.001, Es r=−0.44, p=0.009; correlation of LGE%LV and: GLS r=0.41, p=0.015, Es: r=−0.4, p=0.02, and Ea: r=−0.41, p=0.02). Conclusion Regression of fibrosis and cellular hypertrophy determine improved myocardial function and recovery from heart failure following TAVR. Prognostic implications of the observed changes will need to be explored next to identify makers and therapeutic targets for optimized management of these patients. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): German Research Foundation (DFG, CRC 1002, D1)

Higher pulsatile index in carotid arteries is associated with adverse outcomes in patients treated by left ventricular assist device

Abstract Introduction Better understanding of vascular changes in patients after implantation of left ventricular assist devices (LVAD) is important to understand and prevent complications of this therapy. Currently, there is substantial lack of data regarding the impact of changes in carotid territory on clinical events in this population. Our aim was to analyze the association between carotid flow patterns and atherosclerotic changes with serious clinical events after LVAD implantation in a prospective single-center study. Methods Eighty five patients were included (Heart mate II, n=34; Heart mate 3, n=51; mean age 55±15 years; 13 women). Pulsatile and resistance indexes were calculated and atherosclerotic changes (Belcaro score) were assessed using triplex ultrasound at the 3rd and 6th month after LVAD implantation. Basic clinical and laboratory data were also included into the analyses. The median follow-up time was 982 days [IQR 472–1431]. Results Pulsatile and resistance index significantly increased between 3rd and 6th month (p=0.036 and p=0.012, respectively). Belcaro score did not change significantly. During the follow-up, 17 patients died, 4 due to stroke. Another 4 patients suffered from non-fatal stroke. Pulsatile index measured at 3rd month was associated with an increased risk of composite outcome of stroke, GIT hemorrhage and all-cause mortality (HR 10.6, 95% CI 2.0–55.2, p=0.005) only in the group of HeartMate 3 patients, while not in patients with HeartMate II (HR 0.96, 95% CI 0.07–12.4, p=0.97), p for interaction between groups 0.04. Association between pulsatile index and the risk of adverse events in patients with HeartMate 3 remained significant after adjustments for age, cause of heart failure and INTERMACS score. Conclusion Among patients after LVAD implantation, assessment of carotid flow patterns, pulsatile index in particular, may identify individuals at increased risk of serious clinical complications. Future studies are needed to understand mechanisms leading to increase flow pulsatility in this population. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of Health of the Czech Republic

Head-to-head comparison of MAGGIC-HF, SHFM and BCN-Bio HF scores

Abstract Background Three heart failure (HF) web-based risk scores are currently used in clinical practice. Two only include clinical variables; one adds biomarkers, known to refine pathophysiological pathways in HF and to improve mortality prediction. Objective To assess inter-score agreement and to compare mortality prediction discrimination between MAGGIC-HF risk score, Seattle HF Model (SHFM) and Barcelona Bio-HF Risk Calculator (BCN Bio-HF), which includes both clinical and biomarker variables (NTproBNP). Methods Out of 1745 consecutive patients with HF from different etiologies admitted at our Unit from May 2006 to November 2018, 1689 with NTproBNP measurement at first visit were included. Absolute and consistency intraclass correlation coefficient (ICC) at individual level among the three risk estimation tools was assessed. Bland Altman graphics were used to illustrate the differences between scores across the broad spectrum of mortality risk. Discrimination of the three prediction tools was compared by AUC of the ROC curves for 1-, 3- and 5-year all-cause mortality. Patients used previously to derivate the BCN Bio-HF were excluded. Results Patients age 66.3±13.3 years, 70.4% men, LVEF 36.4%±14.4, ischemic etiology 43.7%. Absolute ICC was poor for the three tools (from 0.18 [–0.006 to 0.35] to 0.53 [0.42 to 0.62], while consistency ICC was slightly better (from 0.28 [0.24 to 0.33] to 0.57 [0.53 to 0.60], being highest the ICC of MAGGIC-HF and BCN Bio-HF. Correlation was better among scores in low-mortality risk profile patients but clinical scores tended to infraestimate the risk in comparison with the BCN Bio-HF in high-risk patients (Figure). Discrimination was numerically better with the BCN Bio-HF at every time risk (Table), significantly better when compared with SHFM. Conclusions In comparison with other clinical scores, the BCN Bio-HF calculator predicted better higher mortality risk. Correlation was globally poor for the three tools at individual level, although improved in the low risk patients. Discrimination tended to be numerically better with the BCN Bio-HF calculator, reaching statistical significance when compared with the SHFM. Bland Altman agreement among tools Funding Acknowledgement Type of funding source: None

How mortality risk estimated by MAGGIC-HF, SHFM and BCN-Bio HF scores is modified after 12-month management in a multidisciplinary HF Clinic

Abstract Background Heart failure (HF) contemporary management has significantly improved over the past two decades leading to better survival. How application of the contemporary HF management guidelines affects the risk of death estimated by available web-based risk scores is not elucidated. Objective To assess changes in mortality risk prediction after a after a 12-month management period in a multidisciplinary HF Clinic. Methods Out of 1,689 consecutive patients with HF admitted at our ambulatory HF Clinic from May 2006 to November 2018, those who completed one year follow-up were considered for the study. Patients without NTproBNP measurement or with more than 3 missing variables for risk estimation were excluded. Three contemporary web-based HF risk scores were evaluated: MAGGIC-HF, Seattle HF Model (SHFM) and the Barcelona Bio-HF Calculator containing NTproBNP (BCN Bio-HF). Risk of all-cause death at one year and at 3 years were calculated at baseline and re-evaluated after 12-month management in a multidsisciplinary HF Clinic. Wilcoxon paired data test was used to compare changes in mortality risk estimation over time and test equality of matched pairs for comparing estimated change among tools. 442 patients used to derive the Barcelona Bio-HF Calculator were excluded for discrimination purposes. Results 1,157 patients were included (age 65.7±12.7 years, 70.4% men). A significant reduction in mortality risk estimation was observed with the three HF risk scores evaluated at 12-months (Table). The BCN Bio-HF model showed significantly different changes in risk estimation, fact that indeed was partnered with numerically better discrimination. AUC at 1 and 3 years, respectively, were: BCN Bio-HF (0.773 and 0.775), MAGGIC HF (0.686 and 0.748) and SHFM (0.773 and 0.739). Conclusions The three web-based risk scores evaluated showed a significant reduction in mortality risk estimation after 12 month management in a multidisciplinary HF Clinic. The BCN Bio-HF score showed higher reduction in estimated risk, together with better discrimination, likely because it incorporates contemporary treatment and use of biomarkers. Funding Acknowledgement Type of funding source: None

Association of Exhaled Carbon Monoxide With Ideal Cardiovascular Health, Circulating Biomarkers, and Incidence of Heart Failure in the Framingham Offspring Study.

BackgroundExhaled carbon monoxide (eCO) is directly associated with traditional cardiovascular disease risk factors and incident cardiovascular disease. However, its relation with the cardiovascular health score and incidence of heart failure (HF) has not been investigated.Methods and ResultsWe measured eCO in 3521 Framingham Heart Study Offspring participants attending examination cycle 6 (mean age 59 years, 53% women). We related the cardiovascular health score (composite of blood pressure, fasting plasma glucose, total cholesterol, body mass index, smoking, diet, and physical activity) to eCO adjusting for age, sex, and smoking. Higher cardiovascular health scores were associated with lower eCO (β=−0.02, P<0.0001), even among nonsmokers. Additionally, C‐reactive protein, plasminogen activator inhibitor‐1, fibrinogen, growth differentiation factor‐15, homocysteine, and asymmetrical dimethylarginine were positively associated with eCO (P≤0.003 for all). The age‐ and sex‐adjusted and multivariable‐adjusted heritabilities of eCO were 49.5% and 31.4%, respectively. Over a median follow‐up of 18 years, 309 participants (45% women) developed HF. After multivariable adjustment, higher eCO was associated with higher risk of HF (hazards ratio per SD increment: 1.39; 95% CI, 1.19–1.62 [P<0.001]) and with higher risk of HF with reduced ejection fraction (N=144 events; hazard ratio per SD increment in eCO: 1.43; 95% CI, 1.15–1.77 [P=0.001]).ConclusionsIn our community‐based sample, higher levels of eCO were associated with lower cardiovascular health scores, an adverse cardiovascular biomarker profile, and a higher risk of HF, specifically HF with reduced ejection fraction. Our findings suggest that carbon monoxide may identify a novel pathway to HF development.

Efficacy and Safety of Kudzu Flower-Mandarin Peel on Hot Flashes and Bone Markers in Women during the Menopausal Transition: A Randomized Controlled Trial.

This randomized controlled study aimed to assess the efficacy and safety of an extract mixture of kudzu flower and mandarin peel (KM) on hot flashes (HFs) and markers of bone turnover in women during the menopausal transition. Healthy women aged 45–60 years with the menopausal HFs were randomly assigned in a 1:1 ratio to either KM (1150 mg/day) or placebo arms for 12 weeks (n = 84). The intent-to-treat analysis found that compared with the placebo, the KM significantly attenuated HF scores (p = 0.041) and HF severities (p < 0.001), with a mean difference from baseline to week 12. The KM also improved bone turnover markers, showing a significant reduction in bone resorption CTx (p = 0.027) and a tendency of increasing bone formation OC relative to the placebo. No serious adverse events and hormonal changes were observed in both groups. These findings suggest that KM consumption may improve the quality of life in ways that are important to symptomatic menopausal women.

Differential prognostic accuracy of right ventricular dysfunction, the Seattle heart failure model and the MAGGIC score in patients with severe mitral regurgitation undergoing the MitraClip® procedure.

BackgroundMitraClip ® (MC) is an established procedure for severe mitral regurgitation (MR) in patients deemed unsuitable for surgery.Right ventricular dysfunction (RVD) is associated with a higher mortality risk. The prognostic accuracy of heart failure risk scores like the Seattle heart failure model (SHFM) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score in pts undergoing MC with or without RVD has not been investigated so far.MethodsSHFM and MAGGIC score were calculated retrospectively. RVD was determined as tricuspid annular plane systolic excursion (TAPSE) ≤15 mm. Area under receiver operating curves (AUROC) of SHFM and MAGGIC were performed for one-year all-cause mortality after MC.ResultsN = 103 pts with MR III° (73 ± 11 years, LVEF 37 ± 17%) underwent MC with a reduction of at least I° MR. One-year mortality was 28.2%.In Kaplan-Meier analysis, one- year mortality was significantly higher in RVD-pts (34.8% vs 2.8%, p = 0.009).Area under the Receiver Operating Characteristic (AUROC) for SHFM and MAGGIC were comparable for both scores (SHFM: 0.704, MAGGIC: 0.692). In pts without RVD, SHFM displayed a higher AUROC and therefore better diagnostic accuracy (SHFM: 0.776; MAGGIC: 0.551, p < 0.05). In pts with RVD, MAGGIC and SHFM displayed comparable AUROCs.ConclusionRVD is an important prognostic marker in pts undergoing MC. SHFM and MAGGIC displayed adequate over-all prognostic power in these pts. Accuracy differed in pts with and without RVD, indicating higher predictive power of the SHFM score in pts without RVD.

Polygenic Score for β-Blocker Survival Benefit in European Ancestry Patients With Reduced Ejection Fraction Heart Failure.

β-Blockers (BBs) are mainstay therapy for heart failure with reduced ejection fraction. However, individual patient responses to BB vary, which may be partially due to genetic variation. The goal of this study was to derive and validate the first polygenic response predictor (PRP) for BB survival benefit in heart failure with reduced ejection fraction patients. Derivation and validation analyses were performed in n=1436 total HF patients of European descent and with ejection fraction <50%. The PRP was derived in a random subset of the Henry Ford Heart Failure Pharmacogenomic Registry (n=248) and then validated in a meta-analysis of the remaining patients from Henry Ford Heart Failure Pharmacogenomic Registry (n=247), the TIME-CHF (Trial of Intensified Versus Standard Medical Therapy in Elderly Patients With Congestive Heart Failure; n=431), and HF-ACTION trial (Heart Failure: a Controlled Trial Investigating Outcomes of Exercise Training; n=510). The PRP was constructed from a genome-wide analysis of BB×genotype interaction predicting time to all-cause mortality, adjusted for Meta-Analysis Global Group in Chronic Heart Failure score, genotype, level of BB exposure, and BB propensity score. Five-fold cross-validation summaries out to 1000 single-nucleotide polymorphisms identified optimal prediction with a 44 single-nucleotide polymorphism score and cutoff at the 30th percentile. In validation testing (n=1188), greater BB exposure was associated with reduced all-cause mortality in patients with low PRP score (n=251; hazard ratio, 0.19 [95% CI, 0.04-0.51]; P=0.0075) but not high PRP score (n=937; hazard ratio, 0.84 [95% CI, 0.53-1.3]; P=0.448)-a difference that was statistically significant (P interaction, 0.0235). Results were consistent regardless of atrial fibrillation, ejection fraction (≤40% versus 41%-50%), or when examining cardiovascular death. Among patients of European ancestry with heart failure with reduced ejection fraction, a PRP distinguished patients who derived substantial survival benefit from BB exposure from a larger group that did not. Additional work is needed to prospectively test clinical utility and to develop PRPs for other population groups and other medications.

The Impact of a Nurse-Led Syncope Clinic: Experience from a single UK tertiary center.

BackgroundSyncope is a leading cause of hospital admission and is associated with significant morbidity and mortality. Our Syncope Clinic commenced in 2014 and we sought to evaluate its impact on outcomes (1‐yr mortality and syncope re‐hospitalization) in patients discharged following syncope admission.MethodsA single‐center study of all consecutive patients discharged with syncope (ICD‐10 R55) between April 2012 and 2017. Patient demographics, comorbidities, hospital stay, syncope re‐hospitalization, and mortality at one‐year were collected. Those subsequently referred and seen in Syncope Clinic were compared with those who were not and predictors of poor outcome were evaluated.ResultsIn total 2950 patients were discharged from hospital with syncope (median age: 73years, 51% male) with 1220 (41%) discharged same‐day; after commencement of Syncope Clinic 231were subsequently reviewed here. Overall mortality was 11%, which was lower in the Syncope Clinic group (3% vs 12%, P < .001). Temporal analysis revealed reduced re‐hospitalization following commencement of Syncope Clinic (2% vs 6%, P = .027). Independent predictors of mortality were increasing age (HR 1.03, 95% CI 1.03‐1.04), AF (HR 1.6, 95% CI 1.2‐2.1), HF (HR 2.2, 95% CI 1.6‐3.0), COPD (HR 1.9, 95% CI 1.4‐2.7), and CHADS2 score ≥ 1 (HR 1.45, 95% CI 1,12‐1.87). Syncope Clinic attendance was associated with reduced mortality (HR 0.3, 95% CI 0.1‐0.6).ConclusionsSyncope patients discharged from hospital had reduced 1yr mortality if seen in subsequent Syncope Clinic. Independent predictors of mortality were COPD, HF, AF, and CHADS2 ≥1. Prospective randomized trials of Syncope Clinics are warranted.

Changes in Hospital Income, Use, and Quality Associated With Private Equity Acquisition

Rigorous evidence describing the relationship between private equity acquisition and changes in hospital spending and quality is currently lacking. To examine changes in hospital income, use, and quality measures that may be associated with private equity acquisition. This cohort study identified 204 hospitals acquired by private equity firms from 2005 to 2017 and 532 matched hospitals not acquired by private equity. Using a difference-in-differences design, this study evaluated changes in net income, charges, charge to cost ratios, case mix index (a measure of reported illness burden), share of discharges for patients with Medicare or Medicaid coverage, discharges per year, and aggregate hospital quality measures associated with private equity acquisition through 3 years after acquisition, adjusted for case mix, hospital beds, calendar year, and adjustment for multiple hypothesis testing. In subgroup analyses, changes in outcomes for private equity-owned Hospital Corporation of America (HCA) hospitals and non-HCA hospitals relative to matched controls were assessed. Eight hospital income and use measures and 3 aggregate hospital quality measures were examined. Relative to 532 control hospitals, the 204 private equity-acquired hospitals showed a mean increase of $2 302 391 (95% CI, $956 660-$3 648 123; P = .009) in annual net income, an increase of $407 (95% CI, $296-$518; P < .001) in total charge per inpatient day, an increase of 0.61 (95% CI, 0.48-0.73; P < .001) in emergency department charge to cost ratio, an increase of 0.31 (95% CI, 0.26-0.37; P < .001) in total charge to cost ratio, an increase of 0.02 (95% CI, 0.01-0.02; P = .007) in case mix index, and a decrease of 0.96% (95% CI, 0.46%-1.45%; P = .002) in share of Medicare discharges. Medicaid's share of discharges (-0.16%; 95% CI, -0.86% to 0.53%; P > .99) and total hospital discharges (98; 95% CI, -54 to 250; P > .99) did not change differentially in a statistically significant manner. The aggregate quality score for acute myocardial infarction increased by 3.3% (95% CI, 1.6%-5.0%; P = .002), and the aggregate score for pneumonia increased by 2.9% (95% CI, 1.8%-3.9%; P < .001) in private equity-acquired hospitals relative to controls. The aggregate score for heart failure (1.3%; 95% CI, -0.2% to 2.7%; P = .92) did not differentially change in a statistically significant manner. In subgroup analyses, HCA hospitals showed similar findings to the entire sample. Among non-HCA hospitals, the only statistically significant relative changes were the increase in the emergency department charge to cost ratio (0.30; 95% CI, 0.12-0.48; P = .02) and the decrease in Medicare's share (-1.15%; 95% CI, -1.88% to -0.43%; P = .02). Non-HCA hospitals showed a decrease in the aggregate heart failure score (-3.3%; 95% CI, -5.3% to -1.3%; P = .01) and no statistically significant changes in the aggregate score for acute myocardial infarction (2.4%; 95% CI, -0.7% to 5.4%; P > .99) or pneumonia (0.2%; 95% CI, -1.4% to 1.7%; P > .99). Hospitals acquired by private equity were associated with larger increases in net income, charges, charge to cost ratios, and case mix index as well as with improvement in some quality measures after acquisition relative to nonacquired controls. Heterogeneity in some findings was observed between HCA and non-HCA hospitals.

Development and Validation of a Electrocardiographic Diagnostic Score of Heart Failure Among Patients with Hypertension Attending a Tertiary Hospital in Ibadan, Nigeria: The RISK-HHF Case-Control Study.

ObjectivesHypertension is the leading cause of HF in sub-Saharan Africa. Electrocardiography (ECG) is a cheap and easily available stratification tool for the diagnosis and prognostication of individuals with hypertension. The aim of this study was to develop an ECG-based HF diagnostic score among patients with hypertension attending a specialist cardiology clinic.MethodsOne hundred and one (101) case-control age- and sex-matched pairs were recruited. The study population were adults with a clinical diagnosis of hypertensive HF failure (cases) and systemic hypertension without HF (controls). Participants underwent clinical assessment and ECG. Associations between ECG variables and HF risk were tested with chi square test. Logistic regression modelling (age- and sex adjusted) was trained on a random subset of participants and tested on the remaining participants to determine the ECG abnormalities that are diagnostic of HF and develop a HF diagnostic score. The HF diagnostic score was then validated in an independent dataset of the ECG-Hypertension Audit. Goodness of fit and c-statistics of the HF summed diagnostic score in the training, testing and validation datasets are presented. A two-sided p value of <0.05 was considered statistically significant.ResultsThe independent ECG diagnostic markers of HF among hypertensive patients in this study in decreasing order of effect size were sinus tachycardia (aOR: 7.72, 95% CI: 2.31-25.85). arrhythmia (aOR: 7.14, 95% CI: 2.57-19.86), left ventricular hypertrophy (aOR: 4.47; 1.85-10.77) and conduction abnormality (aOR: 3.41, 95% CI: 1.21-9.65). The HF summed diagnostic score showed excellent calibration and discrimination in the training (Hosmer Lemeshow p = 0.90; c-statistic 0.82; 95% CI 0.76–0.89) and test samples (Hosmer Lemeshow p=0.31; c-statistic 0.73 95% CI 0.60 to 0.87) of the derivation cohort and an independent validation audit cohort (Hosmer Lemeshow p = 0.17; c-statistic 0.79 95% CI 0.74 to 0.84) respectively. The model showed high diagnostic accuracy in individuals with different intermediate pre-test probabilities of HF.ConclusionsA ECG based HF score consisting of sinus tachycardia, arrhythmia, conduction abnormality and left ventricular hypertrophy is diagnostic of HF especially in those with intermediate pre-test probability of HF. This has clinical importance in the stratification of individuals with systemic hypertension.

Prognostic value of pupil area for all‐cause mortality in patients with heart failure

AimsThe area of the pupil can be used as an indicator of autonomic function. However, the relation between pupil area and prognosis in heart failure (HF) patients remains unclear. This study was performed to examine whether pupil area can be used as a prognostic indicator in patients with HF.Methods and resultsThis retrospective review was performed in 870 consecutive patients (mean age: 67.0 ± 14.1 years, 37.0% women) hospitalized for acute HF. Pupil area was measured with a pupilometer at least 7 days after hospitalization for HF. The primary endpoint was all‐cause mortality, and the secondary endpoint was readmission due to HF. A total of 131 patients died, and 328 patients were readmitted because of HF over a median follow‐up of 1.9 (interquartile range: 1.0–3.7 years) years. After adjustment for several pre‐existing prognostic factors, including Seattle Heart Failure Score (SHFS), pupil area was shown to be independently associated with all‐cause mortality (hazard ratio: 0.72; 95% confidence interval: 0.59–0.88; P = 0.001) and readmission due to HF (hazard ratio: 0.82; 95% confidence interval: 0.73–0.93; P = 0.003). Addition of pupil area to SHFS significantly increased the area under the receiver‐operating characteristic curve for all‐cause mortality (0.69 vs. 0.72, respectively; P = 0.034).ConclusionsPupil area is an independent predictor of all‐cause mortality and readmission due to HF and adds prognostic information to SHFS in patients with HF. The results presented here suggest that pupil area may be useful as a prognostic marker in patients with HF.

The Stanford acute heart failure symptom score for patients hospitalized with heart failure

Currently, there are no simple tools to evaluate the acute heart failure (HF) symptom severity in children hospitalized with acute decompensated HF (ADHF). We sought to develop an inpatient HF score (HFS) that could be used as a clinical tool and for clinical trials. Pediatric HF clinicians at Stanford reviewed the limitations of existing HFSs, which include lack of calibration to the inpatient setting, omission of gastrointestinal symptoms, need for multiple age-based tools, and scores that prioritize treatment intensity over patient symptoms. To address these, we developed an acute HFS corresponding to the 3 cardinal symptoms of HF: difficulty with breathing, feeding, and activity. The score was iteratively improved over a 3-year pilot phase until no further changes were made. The inter-rater reliability (IRR) across a range of providers was assessed using the final version. Peak HFSs were analyzed against mortality and length of stay (LOS) for all pediatric HF discharges between July and October 2019. The final HFS was a 4-point ordinal severity score for each of the 3 symptom domains (total score 0-12). Among clinicians who scored 12 inpatients with ADHF simultaneously, the intraclass correlation (ICC) was 0.94 (respiratory ICC = 0.89, feeding ICC = 0.85, and activity ICC = 0.80). Score trajectory reflected our clinical impression of patient response to HF therapies across a range of HF syndromes including 1- and 2-ventricle heart disease and reduced or preserved ejection fraction. Among the 28 patients hospitalized during a 3-months period (N = 28), quartiles of peak score were associated with LOS (p < 0.01) and in-hospital mortality (p < 0.01): HFS 0 to 3 (median LOS of 5 days and mortality of 0%), HFS 4 to 6 (median LOS of 18 days and mortality of 0%), HFS 5 to 9 (median LOS of 29 days and mortality of 23%), and HFS 10 to 12 (median LOS of 121 days and mortality of 50%). This simple acute HFS may be a useful tool to quantify and monitor day-to-day HF symptoms in children hospitalized with ADHF regardless of etiology or age group. The score has excellent IRR across provider levels and is associated with major hospital outcomes supporting its clinical validity. Validation in a multicenter cohort is warranted.

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.

Persistent congestion, renal dysfunction and inflammatory cytokines in acute heart failure: a prognosis study

Chronic kidney dysfunction (CKD) and persistent congestion influence heart failure prognosis, but little is known about the role of inflammation in this association. We assessed the relationship between inflammatory biomarkers, persistent congestion and CKD and their prognostic implications in patients with acute heart failure. We enrolled 97 hospitalised patients (mean age: 66 ± 12 years, ejection fraction: 30 ± 8%) with acute heart failure. Before discharge, congestion was assessed using a heart failure scoring system on the basis of Framingham criteria. Circulating levels of high-sensitivity C-reactive protein, TGF-β-1, IL-1, IL-6, IL-10, TNF-α, soluble tumour necrosis factor receptor type 1 and 2 were measured. Patients were divided into four groups according to the presence of CKD (estimated glomerular filtration rate <60 ml/min/1.73 m) and congestion (Framingham heart failure score ≥2). The primary end point was the combination of death and rehospitalisation for acute heart failure. During a median follow-up of 32 months, 37 patients died and 14 were rehospitalised for acute heart failure. Patients with CKD and congestion had significantly higher TNF-α (P = 0.037), soluble tumour necrosis factor receptor type 1 (P = 0.0042) and soluble tumour necrosis factor receptor type 2 (P = 0.001), lower TGF-β-1 (P = 0.02) levels, and the worst outcome (P < 0.0001). Congestion (P = 0.01) and CKD (P = 0.02) were independent predictors of the end-point together with N-terminal prohormone of brain natriuretic peptide (P = 0.002) and TNF-α (P = 0.004). TNF-α attenuated the direct relation between CKD, congestion and outcome, explaining 40% of the difference in the outcome. In patients hospitalised with acute heart failure, the prognostic impact of persistent congestion and CKD is associated with increased cytokine levels, which may also interfere with the outcome.

Intracoronary Injection of Autologous CD34+ Cells Improves One-Year Left Ventricular Systolic Function in Patients with Diffuse Coronary Artery Disease and Preserved Cardiac Performance—A Randomized, Open-Label, Controlled Phase II Clinical Trial

This phase II randomized controlled trial tested whether intracoronary autologous CD34+ cell therapy could further improve left ventricular (LV) systolic function in patients with diffuse coronary artery disease (CAD) with relatively preserved LV ejection fraction (defined as LVEF >40%) unsuitable for coronary intervention. Between December 2013 and November 2017, 60 consecutive patients were randomly allocated into group 1 (CD34+ cells, 3.0 × 107/vessel/n = 30) and group 2 (optimal medical therapy; n = 30). All patients were followed for one year, and preclinical and clinical parameters were compared between two groups. Three-dimensional echocardiography demonstrated no significant difference in LVEF between groups 1 and 2 (54.9% vs. 51.0%, respectively, p = 0.295) at 12 months. However, compared with baseline, 12-month LVEF was significantly increased in group 1 (p < 0.001) but not in group 2 (p = 0.297). From baseline, there were gradual increases in LVEF in group 1 compared to those in group 2 at 1-month, 3-months, 6-months and 12 months (+1.6%, +2.2%, +2.9% and +4.6% in the group 1 vs. −1.6%, −1.5%, −1.4% and −0.9% in the group 2; all p < 0.05). Additionally, one-year angiogenesis (2.8 ± 0.9 vs. 1.3 ± 1.1), angina (0.4 ± 0.8 vs. 1.8 ± 0.9) and HF (0.7 ± 0.8 vs. 1.8 ± 0.6) scores were significantly improved in group 1 compared to those in group 2 (all p < 0.001). In conclusion, autologous CD34+ cell therapy gradually and effectively improved LV systolic function in patients with diffuse CAD and preserved LVEF who were non-candidates for coronary intervention (Trial registration: ISRCTN26002902 on the website of ISRCTN registry).

Minimal clinically important difference in quality of life scores for patients with heart failure and reduced ejection fraction.

While the associations of health-related quality of life scores in heart failure (HF) [e.g. the Kansas City Cardiomyopathy Questionnaire (KCCQ)] with clinical outcomes are well established, their interpretation in the context of what magnitudes of change are clinically important to patients is less clear. The main objective of this study was to correlate the changes in the KCCQ and Patient Global Assessment (PGA) in patients with HF with reduced ejection fraction (HFrEF) to determine minimal clinically important difference (MCID). We analysed data from 459 patients of the FAIR-HF trial. Both KCCQ and PGA were assessed at 4 and 24 weeks after enrolment. An anchor-based approach was used to calculate MCID at week 4 and 24. PGA was chosen as the clinical anchor against which changes in the KCCQ scores were calibrated. For each category of change in PGA, the corresponding differences were calculated by the mean scores of various domains of KCCQ along with 95% confidence intervals (CIs). There was fair correlation between PGA and changes in overall summary scores (OSS) (r=0.31; P < 0.001), clinical summary scores (CSS) (r=0.36; P < 0.001) and physical limitation scores (PLS) (r=0.31; P < 0.001) from baseline to week 4. KCCQ OSS, CSS and PLS MCID for 'little improvement' at week 4 were 3.6 (1.0-6.2), 4.5 (1.8-7.2) and 4.7 (1.4-8.0) points, respectively. OSS, CSS and PLS MCID for 'little improvement' at week 24 were 4.3 (0.2-8.4), 4.5 (0.5-8.5) and 4.0 (-0.9-9.0) points, respectively. The MCID threshold for KCCQ score was generally consistent and numerically lower than the threshold of 5-point change considered for clinical outcome prognosis and were stable between 4 and 24 weeks. This suggests that even changes smaller than the traditional 5-point improvements in KCCQ may be clinically meaningful. Also, these results can aid in the clinical interpretation of patient-reported outcomes, and better endpoint selection in future studies.

Catheter ablation of atrial fibrillation in heart failure: clinical, prognostic, and echocardiographic outcome.

Catheter ablation (CA) for atrial fibrillation (AF) in heart failure (HF) patients is associated with a lower rate of cardiac events compared with medical therapy. This study deals with the clinical, echocardiographic, and prognostic outcomes in these patients. Prognostic scores, as MAGGIC (Meta-analysis Global Group in Chronic Heart Failure) score, may help to predict the outcomes. From a single center, 47 patients with AF, HF, and left ventricular ejection fraction (LVEF) < 50% underwent CA. The primary endpoints were NYHA functional class, LVEF, and MAGGIC score. The median age of patients was 59years; 49% had paroxysmal AF. At 12months, a significant improvement of NYHA class (median before II [interquartile range (IQR) II-III] vs median after I [IQR I-II]) and of LVEF (median before 44% [IQR 37-47] vs median after 55% [IQR49-57]) was observed (p value < 0.001). The MAGGIC 1-year and 3-year probability of death was estimated before (mean score 13 [IQR 11-17]) and at 12-month (mean score 11 [IQR 8-13]), showing a significant decrease in the probability of death (p value <0.001). At 12-month, a lower LVEF was associated with more HF hospitalizations (p value 0.035). Coronary artery disease (CAD) (HR 5, p value 0.035) and MAGGIC score (HR 1.2, p value 0.030) were predictors of HF hospitalization. CA for AF in HF patients was associated with a significant improvement of NYHA functional class and LVEF and a higher life expectation. CAD history, LVEF < 40%, and MAGGIC score before ablation were predictors of HF hospitalization.