Serially measured cytokines and cytokine receptors in relation to clinical outcome in patients with stable heart failure

Abstract Background Activation of the inflammatory response in heart failure (HF) may initially serve as a compensatory mechanism. However, on the longer term, this physiological phenomenon can become disadvantageous. Temporal patterns of inflammatory proteins other than CRP have not yet been investigated in patients with stable HF. Purpose We aimed to evaluate the association of 17 serially measured cytokines and cytokine receptors with clinical outcome in patients with stable heart failure. Methods In 263 patients, 1984 serial, tri-monthly blood samples were collected during a median follow-up of 2.2 (IQR: 1.4–2.5) years. The primary endpoint (PE) composed of cardiovascular mortality, HF-hospitalization, heart transplantation, and LVAD. We selected baseline blood samples in all patients, as well as the two samples closest to the primary endpoint, and the last sample available in event-free patients. Thus, in 567 samples we measured 17 cytokines and cytokine receptors using the Olink Proteomics Cardiovascular III multiplex assay. Associations between biomarkers and PE were investigated by joint modelling. Results Median age was 68 (IQR: 59–76) years, with 72% men, 74% NYHA class I-II and a median ejection fraction of 30% (23–38%). 70 patients reached a PE. After adjustment for clinical characteristics (age, sex, diabetes, atrial fibrillation, NYHA class at baseline, diuretics and systolic blood pressure), 7 biomarkers were associated with the PE (Figure). Interleukin-1 receptor type 1 (IL1RT1) showed the strongest association: HR 2.65 [95% CI: 1.78–4.21]) per standard deviation change in level (NPX) at any point in time during follow-up, followed by Tumor necrosis factor receptor 1 (TNF-R1): 2.25 [1.66–3.08], and C-X-C motif chemokine 16 (CXCL16): 2.18 [1.59–3.04]. After adjustment for baseline N-terminal pro–B-type natriuretic peptide, high-sensitive troponin T and C-reactive protein however, only IL1RT1 and TNF-R1 remained significantly associated with the PE. Conclusion Repeatedly measured levels of several cytokines and cytokine receptors are independently associated with clinical outcome in stable HF patients. These results suggest that repeated measurements of these biomarkers, in addition to established cardiac biomarkers, may contribute to personalized risk assessment and herewith better identify high-risk patients. Figure 1. Associations between levels of cytokines and cytokine receptors and the primary endpoint. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by the Jaap Schouten Foundation and the Noordwest Academie.

Download Full-text

Twin peaks diversity with sacubitril/valsartan treatment responses in cardiomyopathic heart failure patients of non-ischemic compared to ischemic etiologies

European Heart Journal ◽

10.1093/ehjci/ehaa946.1056 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

H.Y Chang ◽

W.R Chiou ◽

P.L Lin ◽

C.Y Hsu ◽

C.T Liao ◽

...

Keyword(s):

Heart Failure ◽

Primary Endpoint ◽

Ischemic Cardiomyopathy ◽

Ventricular Remodeling ◽

Left Ventricular Ejection ◽

Funding Source ◽

Heart Failure Patients ◽

Twin Peaks ◽

All Cause Mortality

Abstract Background Ischemic cardiomyopathy (ICM) has been associated with increased mortality when compared with non-ischemic cardiomyopathy (NICM) from several heart failure (HF) cohorts. Instead, PARADIGM study demonstrated similar event rates of cardiovascular (CV) death, all-cause mortality and HF readmissions between ICM and NICM patients. Although the beneficiary effect of sacubitril/valsartan (SAC/VAL) compared to enalapril on these endpoints was consistent across etiologic categories, PARADIGM study did not analyze the effect of ventricular remodeling of SAC/VAL on patients with different HF etiologies, which may significantly affect treatment outcomes. Purpose We aim to compare alterations of left ventricular ejection fraction (LVEF) following SAC/VAL treatment and its association with clinical outcomes in patients with different HF etiologies. Methods Treatment with angiotensin receptor neprilysin inhibitor for Taiwan heart failure patients (TAROT-HF) study is a multicenter study which enrolled 1552 patients with LVEF <40%, whom had been on SAC/VAL treatment from 9 hospitals between 2017 and 2018. After excluding patients without having follow-up echocardiographic studies, patients were grouped by HF etiologies and by LVEF changes following treatment for 8-month period. LVEF improvement ≥15% was defined as “significant improvement”, 5–15% as “marginal improvement”, and <5% or worse as “lack of improvement”. The primary endpoint was a composite of CV death or a first hospitalization for HF. Mean follow-up period was 726 days. Results A total of 1230 patients were analyzed. Patients with ICM were significantly older, more male, and prone to have associated hypertension and diabetes. On the other hand, patients with NICM had lower LVEF and higher likelihood of atrial fibrillation. LVEF increase was significantly greater in patients with NICM compared to those with ICM (11.2±12.4% vs. 6.9±9.8, p<0.001). The effect of ventricular remodeling of SAC/VAL on patients with NICM showed twin peaks diversity (Significant improvement 37.1%, lack of improvement 42.3%), whereas in patients with ICM the proportions of significant, marginal and lack of improvement groups were 19.4%, 28.2% and 52.4%, respectively. The primary endpoint showed twin peaks diversity also in patients with NICM in line with LVEF changes: adjusted HR for patients with NICM and significant improvement was 0.41 (95% CI 0.29–0.57, p<0.001), for patients with NICM and lack of improvement was 1.54 (95% CI 1.22–1.94, p<0.001). Analyses for CV death, all-cause mortality, and HF readmission demonstrated consistent results. Conclusion Patients with NICM had higher degree of LVEF improvement than those with ICM following SAC/VAL treatment, and significant improvement of LVEF in NICM patients may indicate favorable outcome. NICM patients without response to SAC/VAL treatment should serve as an indicator for poor clinical outcome and warranted meticulous HF management. Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Cheng Hsin General Hospital

Download Full-text

Favorable course of tricuspid regurgitation after percutaneous mitral valve repair is associated with improved survival and clinical outcome

European Heart Journal ◽

10.1093/ehjci/ehaa946.1945 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

F Meijerink ◽

J Baan ◽

B.J Bouma

Keyword(s):

Mitral Valve ◽

Clinical Outcome ◽

Mitral Valve Repair ◽

Tricuspid Regurgitation ◽

Nyha Class ◽

Funding Source ◽

Valve Repair ◽

Percutaneous Mitral Valve Repair ◽

All Cause Mortality

Abstract Background Tricuspid Regurgitation (TR) is often present in patients with mitral regurgitation (MR) and is associated with increased mortality and morbidity after percutaneous mitral valve repair (PMVR) using the MitraClip (Abbott Vascular). It is unclear to what extent TR is reduced after PMVR and whether the reduction of TR is related to survival and functional outcome. Purpose The aim of this study was to determine (1) the TR course after PMVR and (2) if this was related to survival and clinical outcome. Methods Patients who underwent PMVR and had complete echocardiographic data at baseline and follow-up were included. TR severity was graded as none, mild, moderate or severe (according to current guidelines) and was determined before treatment and at 6-months of follow up. Favorable TR course was defined as improvement of ≥1 grade or ≤ mild TR at 6-months. Clinical endpoints were all-cause mortality during 1-year of follow-up and improvement in New York Heart Association (NYHA) functional class after 6 months. Results A total of 67 patients were included (mean age 76 years, 57% male, 81% NYHA class ≥3 and 69% baseline TR ≥ moderate). Favorable TR course was achieved in 31 patients (46%) (figure 1A). All-cause mortality at 1 year was 7.5%, and was lower in the favorable TR course group (0% vs. 13.9%, p=0.057) (figure 1B). Improvement in NYHA class at 6-months was seen in 45% of patients without vs. 81% of patients with favorable TR course (p=0.01) (figure 1C). Conclusion A favorable TR course is achieved in 46% of PMVR patients and is associated with improved survival and improvement of NYHA class. The relatively high rate of an unfavorable TR course at 6-months, indicates that interventional treatment of the tricuspid valve might benefit these patients. TR course (A) and NYHA improvement (B) Funding Acknowledgement Type of funding source: Other. Main funding source(s): Abbott

Download Full-text

Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE)

European Heart Journal ◽

10.1093/ehjci/ehaa946.1151 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Tanaka ◽

I Hisauchi ◽

I Taguchi ◽

A Sezai ◽

S Toyoda ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Chronic Heart Failure ◽

Primary Endpoint ◽

Nyha Class ◽

Left Ventricular ◽

Percentage Change ◽

Left Ventricular Ejection ◽

Funding Source

Abstract Background Little is known about the impacts of sodium glucose co-transporter 2 inhibitors on cardiac functional parameters, such as natriuretic peptides, in type 2 diabetes (T2D) patients with concomitant chronic heart failure (CHF). Purpose To compare the effect of canagliflozin with glimepiride, based on changes in N-terminal pro-brain natriuretic peptide (NT-proBNP), in that patient population. Methods This trial was an investigator-initiated, multicenter, prospective, randomized, open-label, blinded-endpoint trial at 34 centers in Japan. Patients with T2D and clinically stable CHF excluding NYHA class IV, randomized to receive canagliflozin 100 mg or glimepiride (starting dose: 0.5 mg), were examined using the primary endpoint of non-inferiority of canagliflozin versus glimepiride, defined as a margin of 1.1 in the upper-limit of the 2-sided 95% confidence interval (95% CI) for the group ratio of percentage change in NT-proBNP at 24 weeks. Results Data analysis of 233 patients (mean age 68.6±10.1 yrs; 75% male) showed mean left ventricular ejection fraction (LVEF) at randomization was 57.6±14.6%, with 71% of patients having a preserved LVEF (≥50%). The ratio of NT-proBNP percentage change was 0.48 (95% CI, −0.13 to 1.59, P=0.226), and therefore did not meet the prespecified non-inferiority margin. However, data stratified according to baseline NT-proBNP levels showed a trend that canagliflozin treatment reduced NT-proBNP levels to a greater extent than in subgroups with elevated levels of NT-proBNP (Figure A). Furthermore, NT-proBNP levels in the canagliflozin group did show a nonsignificant trend lower in the subgroup with preserved LVEF (Figure B), but not in the subgroup with reduced LVEF (Figure C). Additionally, the changes in the NYHA class were comparable between groups (P=0.061) in the overall cohort, whereas in the subgroup with a preserved LVEF canagliflozin caused a significant improvement in NYHA classes compared to that found for glimepiride treatment (P=0.027). Conclusions This trial did not meet the predefined primary endpoint of changes in NT-proBNP levels, with 24 weeks of treatment with canagliflozin relative to glimepiride which together with other recent studies would question the value of continuing to monitor NT-proBNP levels after the initial diagnosis of heart failure. Nevertheless, in a subgroup with preserved LVEF, there was a non-significant trend for canagliflozin treatment to reduce NT-proBNP levels and improve symptoms even in stable HF patients. Further research is therefore warranted to determine whether patients with preserved LVEF, regardless of diabetes status, could potentially benefit from treatment with SGLT2 inhibitors. Changes in NT-proBNP Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Mitsubishi Tanabe Pharma Corporation

Download Full-text

5948Circulating biomarkers of cell adhesion in relation to clinical outcomes in patients with chronic heart failure: the Bio-SHiFT study

European Heart Journal ◽

10.1093/eurheartj/ehz746.0098 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

E Bouwens ◽

V J Van Den Berg ◽

K M Akkerhuis ◽

S Baart ◽

K Caliskan ◽

...

Keyword(s):

Heart Failure ◽

Cell Adhesion ◽

Chronic Heart Failure ◽

Adhesion Molecule ◽

Nyha Class ◽

Temporal Patterns ◽

Blood Biomarkers ◽

Mixed Effect ◽

Two Samples

Abstract Background Cardiovascular inflammation and vascular endothelial dysfunction are present in chronic heart failure (CHF), and cellular adhesion molecules are considered to play a key role in these mechanisms. The temporal patterns of the blood biomarkers involved could provide further insights into these processes. Purpose We aimed to evaluate the prognostic value of the temporal patterns of blood biomarkers of cell adhesion in stable patients with CHF. Methods In 263 patients, a median of 9 (IQR: 5–10) serial, tri-monthly blood samples were collected during a median follow-up of 2.2 (IQR: 1.4–2.5) years. The composite primary endpoint (PE) of cardiovascular mortality, HF-hospitalization, heart transplantation and LVAD was reached in 70 patients. For efficiency, we selected all baseline samples, the two samples closest to a PE, and the last sample available for event-free patients. Thus, in 567 samples we measured twelve biomarkers of cell adhesion using the Olink Proteomics Cardiovascular III multiplex assay. Associations between biomarkers and first PE were investigated by combining linear mixed effect models and Cox regression (so-called joint model). Results Median age was 68 (IQR: 59–76) years, with 72% men and 74% NYHA class I-II. Levels of CD93 (Complement component C1q receptor), CDH5 (VE cadherin), CHI3L1 (Chitinase-3-like protein 1), EPHB4 (Ephrin type-B receptor 4) and JAM-A (Junctional adhesion molecule A) differed at baseline already. The average biomarker evolutions of these markers, and additionally of ICAM-2 (Intercellular adhesion molecule-2), showed different patterns in patients approaching the PE versus those who remained event-free (Figure 1). Repeatedly measured levels of these biomarkers were independently associated with the PE. Corresponding HRs [95% CI] per 1SD increase in log2 level (arbitrary unit) were: CD93: 1.85 [1.29–2.70], CDH5: 1.72 [1.23–2.44], CHI3L1: 2.45 [1.73–3.56], EPHB4: 1.83 [1.33–2.55], ICAM2: 1.74 [1.24–2.46] and JAM-A: 2.07 [1.39–3.18], adjusted for clinical characteristics (age, sex, diabetes, atrial fibrillation, baseline NYHA class, diuretics, systolic blood pressure and eGFR). Figure 1. Average temporal patterns of cell adhesion biomarkers during follow-up. Conclusion CD93, CDH5, CHI3L1, EPHB4, ICAM2 and JAM-A show different patterns as adverse events approach in CHF patients, and their temporal patterns strongly predict clinical outcome. These findings demonstrate the incremental value of repeated measurements of biomarkers of cell adhesion in stable patients with CHF. Acknowledgement/Funding This work was supported by the Jaap Schouten Foundation and the Noordwest Academie.

Download Full-text

Circulating Biomarkers of Cell Adhesion Predict Clinical Outcome in Patients with Chronic Heart Failure

Journal of Clinical Medicine ◽

10.3390/jcm9010195 ◽

2020 ◽

Vol 9 (1) ◽

pp. 195 ◽

Cited By ~ 1

Author(s):

Elke Bouwens ◽

Victor J. van den Berg ◽

K. Martijn Akkerhuis ◽

Sara J. Baart ◽

Kadir Caliskan ◽

...

Keyword(s):

Heart Failure ◽

Cell Adhesion ◽

Chronic Heart Failure ◽

Clinical Outcome ◽

Adhesion Molecule ◽

Temporal Patterns ◽

Cellular Adhesion ◽

Left Ventricular ◽

Blood Samples ◽

Two Samples

Cardiovascular inflammation and vascular endothelial dysfunction are involved in chronic heart failure (CHF), and cellular adhesion molecules are considered to play a key role in these mechanisms. We evaluated temporal patterns of 12 blood biomarkers of cell adhesion in patients with CHF. In 263 ambulant patients, serial, tri-monthly blood samples were collected during a median follow-up of 2.2 (1.4–2.5) years. The primary endpoint (PE) was a composite of cardiovascular mortality, HF hospitalization, heart transplantation and implantation of a left ventricular assist device and was reached in 70 patients. We selected the baseline blood samples in all patients, the two samples closest to a PE, or, for event-free patients, the last sample available. In these 567 samples, associations between biomarkers and PE were investigated by joint modelling. The median age was 68 (59–76) years, with 72% men and 74% New York Heart Association class I–II. Repeatedly measured levels of Complement component C1q receptor (C1qR), Cadherin 5 (CDH5), Chitinase-3-like protein 1 (CHI3L1), Ephrin type-B receptor 4 (EPHB4), Intercellular adhesion molecule-2 (ICAM-2) and Junctional adhesion molecule A (JAM-A) were independently associated with the PE. Their rates of change also predicted clinical outcome. Level of CHI3L1 was numerically the strongest predictor with a hazard ratio (HR) (95% confidence interval) of 2.27 (1.66–3.16) per SD difference in level, followed by JAM-A (2.10, 1.42–3.23) and C1qR (1.90, 1.36–2.72), adjusted for clinical characteristics. In conclusion, temporal patterns of C1qR, CDH5, CHI3L1, EPHB4, ICAM2 and JAM-A are strongly and independently associated with clinical outcome in CHF patients.

Download Full-text

Clinical outcome after MitraClip procedure: role of right ventricle

European Heart Journal ◽

10.1093/eurheartj/ehab724.0130 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

A Barosi ◽

E Gherbesi ◽

S Colombo ◽

A Giavarini ◽

I Cusmano ◽

...

Keyword(s):

Heart Failure ◽

Clinical Outcome ◽

Nyha Class ◽

Left Ventricular ◽

Functional Class ◽

Left Ventricular Ejection ◽

Lv Function ◽

Ventricular Ejection Fraction ◽

Mitraclip System

Abstract Background MitraClip system is a device for percutaneous edge-to-edge repair of the mitral valve in symptomatic patients with severe mitral regurgitation (MR) not eligible for surgery, but frequently heart failure symptoms remain substantial on mid-term follow-up. Recently, right ventricular (RV) to pulmonary arterial (PA) coupling has emerged as a relevant prognostic predictor in heart failure but little is known about its prognostic role in patients after MitraClip implantation. Purpose To identify echocardiographic predictors of clinical outcome after MitraClip procedure, with a particular focus on RV-PA coupling. Methods We retrospectively analyzed the data of patients with severe MR who underwent MitraClip implantation between April 2015 and October 2019 at our Institution. Echocardiographic data were assessed at baseline, 3 and 12 months after the procedure; RV to PA coupling was assessed using the ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP). Functional class was assessed at 12 months of follow-up. Significance level was set to 0.05 and SPSS was used for statistical analysis. Results 41 patients were included (age 77.1±7.3, 71% male, BMI 25.8±5.5). MR was primary, functional and mixed in 22, 76 and 2% of patients, respectively. 1/2/3 mitraclips were implanted in 39/56/5% of patients, respectively. Echocardiographic data at baseline, at 3 and 12 months follow-up are shown in Table. NYHA class at 12 months significantly correlated with TAPSE and PASP at 3 months follow-up echocardiogram (beta coefficient −0.83 and 0.78 respectively). On the contrary, NYHA class did not show a correlation with left ventricular ejection fraction (LVEF) or residual MR grade. At 12 months 44% of patients showed an improvement in NYHA class; these patients had a better TAPSE (22.7±1.3 vs 19.4±4.6 mm), a lower PASP (37.9±10.2 vs 48.5±12.9 mmHg) and a better TAPSE/PASP (0.61±0.2 vs 0.42±0.2) compared to patients who did not improve their functional class, while LVEF and residual MR did not differ. Conclusion In this sample of significant MR undergoing repair with MitraClip System, patients with functional class improvement at 12 months follow-up showed a better RV-coupling without difference in LV function and residual MR. FUNDunding Acknowledgement Type of funding sources: None. Table 1

Download Full-text

Association between self-care and prognosis in 1123 patients with chronic heart failure

European Heart Journal ◽

10.1093/ehjci/ehaa946.1041 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

E Calero ◽

E Hidalgo ◽

R Marin ◽

L Rosenfeld ◽

I Fernandez ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Acute Heart Failure ◽

Nyha Class ◽

Self Care ◽

P Value ◽

Funding Source ◽

Class Iii ◽

Cox Models ◽

Lower Tertile

Abstract Background Self-care is a crucial factor in the education of patients with heart failure (HF) and directly impacts in the progression of the disease. However, little is published about its major clinical implications as admission or mortality in patients with HF. Aims and methods The aim of the study was to analyze time to admission due to acute heart failure and mortality associated with poor self-care in patients with chronic HF. We prospectively recruited consecutive patients with stable chronic HF referred to a nurse-led HF programme. Selfcare was evaluated at baseline with the 9 item European Heart Failure Self-Care Behavior Scale. Scores were standardized and reversed from 0 (worst selfcare) to 100 (better self care). For the purpose of this study we analyzed the associations of worse self-care (defined as scores below the lower tertile of the scale) with demographic, disease-related (clinical) and psychosocial factors in all patients at baseline. Results We included 1123 patients, mean age 72±11, 639 (60%) were male, mean LVEF 45±17 and 454 (40,4%) were in NYHA class III or IV. Mean score of the 9-item ESCBE was 69±28. Score below 55 (lower tertile) defined impaired selfcare behaviour. Those patients with worse self-care had more ischaemic heart disease, more COPD, and they achieved less distance in the 6 minute walking test. Regarding psychosocial items patients in lower tertile of self-care needed a caregiver more frequently, they present more cognitive impairment, depressive symptoms and worse score in terms of health self-perception. Multivariate Cox Models showed that a score below 55 points in 9-item ESCBE was independently associated with higher readmission due to acute heart failure [HR 1.26 (1.02–1.57), p value=0.034] and with mortality [HR 1.24 CI95% (1.02–1.50), p value=0.028] Conclusion Poor self-care measured with the modified 9-item ESCBE was associated with higher risk of admission due to acute decompensation and higher risk of mortality in patients with chronic heart failure. These results highlight the importance of assessing self-care and provide measures to improve them. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Hospital Univesitario de Bellvitge

Download Full-text

Coronary sinus catalase and ceruloplasmin levels predict all-cause mortality in patients with end-stage heart failure awaiting heart transplantation

European Heart Journal ◽

10.1093/ehjci/ehaa946.1005 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

W Szczurek ◽

M Gasior ◽

M Skrzypek ◽

G Kubiak ◽

A Kuczaj ◽

...

Keyword(s):

Heart Failure ◽

Heart Transplantation ◽

Coronary Sinus ◽

Public Institution ◽

Funding Source ◽

Organ Shortage ◽

Number Of Patients ◽

End Stage ◽

Medical University

Abstract Background, As a consequence of the worldwide increase in life expectancy and due to significant progress in the pharmacological and interventional treatment of heart failure (HF), the proportion of patients that reach an advanced phase of disease is steadily growing. Hence, more and more numerous group of patients is qualified to the heart transplantation (HT), whereas the number of potential heart donors has remained invariable since years. It contributes to deepening in disproportion between the demand for organs which can possibly be transplanted and number of patients awaiting on the HT list. Therefore, accurate identification of patients who are most likely to benefit from HT is imperative due to an organ shortage and perioperative complications. Purpose The aim of this study was to identify the factors associated with reduced survival during a 1.5-year follow-up in patients with end-stage HF awating HT. Method We propectively analysed 85 adult patients with end-stage HF, who were accepted for HT at our institution between 2015 and 2016. During right heart catheterization, 10 ml of coronary sinus blood was additionally collected to determine the panel of oxidative stress markers. Oxidative-antioxidant balance markers included glutathione reductase (GR), glutathione peroxidase (GPx), glutathione transferase (GST), superoxide dismutase (SOD) and its mitochondrial isoenzyme (MnSOD) and cytoplasmic (Cu/ZnSOD), catalase (CAT), malondialdehyde (MDA), hydroperoxides lipid (LPH), lipofuscin (LPS), sulfhydryl groups (SH-), ceruloplasmin (CR). The study protocol was approved by the ethics committee of the Medical University of Silesia in Katowice. The endpoint of the study was mortality from any cause during a 1.5 years follow-up. Results The median age of the patients was 53.0 (43.0–56.0) years and 90.6% of them were male. All included patients were treated optimally in accordance with the guidelines of the European Society of Cardiology. Mortality rate during the follow-up period was 40%. Multivariate logistic regression analysis showed that ceruloplasmin (odds ratio [OR] = 0.745 [0.565–0.981], p=0.0363), catalase (OR = 0.950 [0.915–0.98], p=0.0076), as well as high creatinine levels (OR = 1.071 [1.002–1.144], p=0.0422) were risk factors for death during 1.5 year follow-up. Conclusions Coronary sinus lower ceruloplasmin and catalase levels, as well as higher creatinine level are independently associated with death during 1.5 year follow-up. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Medical University of SIlesia, Katowice, POland

Download Full-text

Long-term systolic blood pressure and all-cause mortality in heart failure with preserved ejection fraction: an analysis of the TOPCAT trial

European Heart Journal ◽

10.1093/ehjci/ehaa946.0983 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

P Huang ◽

C Liu

Keyword(s):

Heart Failure ◽

Blood Pressure ◽

Ejection Fraction ◽

Funding Source ◽

Preserved Ejection Fraction ◽

Risk Of Mortality ◽

All Cause Mortality ◽

History Of

Abstract Background Lower systolic blood pressure (SBP) at admission or discharge was associated with poor outcomes in patients with heart failure and preserved ejection fraction (HFpEF). However, the optimal long-term SBP for HFpEF was less clear. Purpose To examine the association of long-term SBP and all-cause mortality among patients with HFpEF. Methods We analyzed participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study. Participants had at least two SBP measurements of different times during the follow-up were included. Long-term SBP was defined as the average of all SBP measurements during the follow-up. We stratified participants into four groups according to long-term SBP: <120mmHg, ≥120mmHg and <130mmHg, ≥130mmHg and <140mmHg, ≥140mmHg. Multivariable adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality associated with SBP level. To assess for nonlinearity, we fitted restricted cubic spline models of long-term SBP. Sensitivity analyses were conducted by confining participants with history of hypertension or those with left ventricular ejection fraction≥50%. Results The 3338 participants had a mean (SD) age of 68.5 (9.6) years; 51.4% were women, and 89.3% were White. The median long-term SBP was 127.3 mmHg (IQR 121–134.2, range 77–180.7). Patients in the SBP of <120mmHg group were older age, less often female, less often current smoker, had higher estimated glomerular filtration rate, less often had history of hypertension, and more often had chronic obstructive pulmonary disease and atrial fibrillation. After multivariable adjustment, long-term SBP of 120–130mmHg and 130–140mmHg was associated with a lower risk of mortality during a mean follow-up of 3.3 years (HR 0.65, 95% CI: 0.49–0.85, P=0.001; HR 0.66, 95% CI 0.50–0.88, P=0.004, respectively); long-term SBP of <120mmHg had similar risk of mortality (HR 1.03, 95% CI: 0.78–1.36, P=0.836), compared with long-term SBP of ≥140mmHg. Findings from restricted cubic spline analysis demonstrate that there was J-shaped association between long-term SBP and all-cause mortality (P=0.02). These association was essentially unchanged in sensitivity analysis. Conclusions Among patients with HFpEF, long-term SBP showed a J-shaped pattern with all-cause mortality and a range of 120–140 mmHg was significantly associated with better outcomes. Future randomized controlled trials need to evaluate optimal long-term SBP goal in patients with HFpEF. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): China Postdoctoral Science Foundation Grant (2019M660229 and 2019TQ0380)

Download Full-text

Benefits of tafamidis in patients with advanced transthyretin amyloid cardiomyopathy

European Heart Journal ◽

10.1093/ehjci/ehaa946.2115 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

C Rapezzi ◽

A.V Kristen ◽

B Gundapaneni ◽

M.B Sultan ◽

M Hanna

Keyword(s):

Disease Severity ◽

Nyha Class ◽

Funding Source ◽

Class Iii ◽

Private Company ◽

Risk Of Death ◽

6Mwt Distance ◽

All Cause Mortality ◽

Amyloid Cardiomyopathy

Abstract Background In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis was shown to be an effective treatment for patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Further assessment of the efficacy of tafamidis in patients with more advanced ATTR-CM would aid treatment decisions. Purpose To characterize the benefits of tafamidis in patients with advanced ATTR-CM. Methods In ATTR-ACT, ATTR-CM patients were randomized to tafamidis (n=264) or placebo (n=177) for 30 months. Efficacy outcomes included all-cause mortality and frequency of cardiovascular (CV)-related hospitalisations. Key secondary endpoints were change from baseline to Month 30 in 6MWT distance and KCCQ-OS score. Efficacy assessments in NYHA Class III patients at baseline (n=141) were a pre-specified analysis. In a post-hoc analysis, mortality and CV-related hospitalizations were assessed in all patients grouped into quartiles of increasing disease severity based on 6MWT distance at baseline. Longer-term all-cause mortality (as of 1 Aug 2019) was assessed in NYHA Class III patients utilizing data from ATTR-ACT patients who enrolled in a long-term, extension study (LTE) and continued treatment with higher dose tafamidis (n=55; median treatment duration 51.6 months); or, if previously treated with placebo, started tafamidis treatment (placebo/tafamidis; n=63 [50.1 months]). Results In advanced ATTR-CM patients (NYHA Class III), tafamidis reduced the risk of death (HR [95% CI] 0.837, [0.541, 1.295], P=0.4253), and the decline in 6MWT distance (LS mean [SE], 31.6 (22.1) m; P=0.1526) and KCCQ-OS score (LS mean [SE], 13.1 (5.0); P=0.0090), vs placebo. Paradoxically, there was a higher frequency of CV-related hospitalizations with tafamidis (RR [95% CI] vs placebo, 1.411 [1.048, 1.900]). In all patients by 6MWT quartile, CV-related hospitalizations/year with tafamidis and placebo increased with disease severity, with the exception that placebo-treated patients in the highest severity quartile had fewer CV-related hospitalisations (0.73) than those in the third quartile (0.92). Mortality with tafamidis and placebo increased, and was greater with placebo, in every quartile (Figure). Survival (NYHA Class III patients in ATTR-ACT and LTE) was improved with high dose tafamidis with longer term follow-up (HR vs placebo/tafamidis [95% CI], 0.6569 [0.4175, 1.0336]; P=0.0692). Conclusions These analyses, including longer-term follow-up, demonstrate that patients with advanced ATTR-CM benefit from tafamidis. The decrease in CV-related hospitalisations in more severe patients treated with placebo suggests that the comparatively greater hospitalisation frequency in NYHA Class III patients treated with tafamidis is a consequence of their lower mortality rate. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This study was sponsored by Pfizer

Download Full-text