P6523M235T polymorphism of ATG: prognostic marker of cardiovascular events in diabetic patients with heart failure with preserved ejection fraction, a 2 year follow-up

Abstract Background Catheter ablation improves clinical outcomes in symptomatic atrial fibrillation (AF) patients with heart failure (HF) with reduced ejection fraction (HFrEF). However, the role of catheter ablation in HF patients with a preserved ejection fraction (HFpEF) is less clear. Purpose To determine the efficacy of catheter ablation of AF in patients with HFpEF relative to those with HFrEF. Methods We performed an extensive literature search and systematic review of studies that compared AF recurrence at one year after catheter ablation of AF in patients with HFpEF versus those with HFrEF. Risk ratio (RR) 95% confidence intervals were measured using the Mantel-Haenszel method for dichotomous variables, where a RR<1.0 favors the HFpEF group. Results Four studies with a total of 563 patients were included, of which 312 had HFpEF and 251 had HFrEF. All patients included were undergoing first time catheter ablation of AF. Patients with HFpEF experienced similar recurrence of AF one year after ablation on or off antiarrhythmic drugs compared to those with HFrEF (RR 0.87; 95% CI 0.69–1.10, p=0.24), as shown in Figure 1. Recurrence of AF was assessed with electrocardiography, Holter monitoring, and/or event monitoring at scheduled follow-up visits and final follow-up. Conclusion Based on the results of this meta-analysis, catheter ablation of AF in patients with HFpEF appears as efficacious in maintaining sinus rhythm as in those with HFrEF. Funding Acknowledgement Type of funding source: None

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Abstract 13497: Prognostic Value of the Combination of the Echocardiographic Derived Pulmonary Artery Wedge Pressure and Body Mass Index in Patients With Heart Failure With Preserved Ejection Fraction: Insights From PURSUIT-HFpEF Registry

Circulation ◽

10.1161/circ.142.suppl_3.13497 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Kumpei Ueda ◽

Shungo Hikoso ◽

Daisaku D Nakatani ◽

Shunsuke Tamaki ◽

Masamichi Yano ◽

...

Keyword(s):

Heart Failure ◽

Body Mass Index ◽

Ejection Fraction ◽

Prognostic Value ◽

Left Ventricular ◽

Preserved Ejection Fraction ◽

Pulmonary Artery Wedge Pressure ◽

Patients With Heart Failure ◽

Wedge Pressure

Background: An elevated pulmonary artery wedge pressure (PAWP), a surrogate of left ventricular filling pressure, is associated with poor outcomes in patients with heart failure (HF). In addition, obesity paradox is well recognized in HF patients and body mass index (BMI) also provides a prognostic information. However, there is little information available on the prognostic value of the combination of the echocardiographic derived PAWP and BMI in patients with HF with preserved ejection fraction (HFpEF). Methods and Results: Patients data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study, which is a prospective multicenter observational registry for acute decompensated heart failure (ADHF) patients with HFpEF. We analyzed 548 patients after exclusion of patients undergoing hemodialysis, patients with in-hospital death, missing follow-up data, or missing data to calculate PAWP or BMI. Body weight measurement and echocardiography were performed just before discharge. PAWP was calculated using the Nagueh formula [PAWP = 1.24* (E/e’) + 1.9] with e’ = [(e’ septal + e’ lateral ) /2]. During a mean follow up period of 1.5±0.8 years, 86 patients had all-cause death (ACD). Multivariate Cox analysis showed that both PAWP (p=0.020) and BMI (p=0.0001) were significantly associated with ACD, independently of age and previous history of HF hospitalization, after the adjustment with gender, left ventricular ejection fraction, NT-proBNP and estimated glomerular filtration rate. Kaplan-Meier curve analysis revealed that there was a significant difference in the risk of ACD when patients were stratified into 3 groups based on the median values of PAWP (17.3) and BMI (21.4). Conclusions: The combination of the echocardiographic derived PAWP and BMI might be useful for stratifying ADHF patients with HFpEF at risk for the total mortality.

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Abstract 12849: Changes in N-terminal Pro Brain Natriuretic Peptide Levels Predicts Mortality and Heart Failure Hospitalization in Patients With Heart Failure and Preserved Ejection Fraction

Circulation ◽

10.1161/circ.132.suppl_3.12849 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Gianluigi Savarese ◽

Camilla Hage ◽

Ulf Dahlström ◽

Pasquale Perrone-Filardi ◽

Lars H Lund

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Total Mortality ◽

Preserved Ejection Fraction ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure ◽

The Impact

Introduction: Changes in N-terminal pro brain natriuretic peptide (NT-proBNP) have been demonstrated to correlate with outcomes in patients with heart failure (HF) and reduced ejection fraction (EF). However the prognostic value of a change in NT-proBNP in patients with heart failure and preserved ejection fraction (HFPEF) is unknown. Hypothesis: To assess the impact of changes in NT-proBNP on all-cause mortality, HF hospitalization and their composite in an unselected population of patients with HFPEF. Methods: 643 outpatients (age 72+12 years; 41% females) with HFPEF (ejection fraction ≥40%) enrolled in the Swedish Heart Failure Registry between 2005 and 2012 and reporting NT-proBNP levels assessment at initial registration and at follow-up were prospectively studied. Patients were divided into 2 groups according the median value of NT-proBNP absolute change that was 0 pg/ml. Median follow-up from first measurement was 2.25 years (IQR: 1.43 to 3.81). Adjusted Cox’s regression models were performed using total mortality, HF hospitalization (with censoring at death) and their composite as outcomes. Results: After adjustments for 19 baseline variables including baseline NT-proBNP, as compared with an increase in NT-proBNP levels at 6 months (NT-proBNP change>0 pg/ml), a reduction in NT-proBNP levels (NT-proBNP change<0 pg/ml) was associated with a 45.2% reduction in risk of all-cause death (HR: 0.548; 95% CI: 0.378 to 0.796; p:0.002), a 50.1% reduction in risk of HF hospitalization (HR: 0.49; 95% CI: 0.362 to 0.689; p<0.001) and a 42.6% reduction in risk of the composite outcome (HR: 0.574; 95% CI: 0.435 to 0.758; p<0.001)(Figure). Conclusions: Reductions in NT-proBNP levels over time are independently associated with an improved prognosis in HFPEF patients. Changes in NT-proBNP could represent a surrogate outcome in phase 2 HFPEF trials.

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Abstract 13570: Diabetes is Probably Associated With Larger Fluid Retention in Patients With Heart Failure With Preserved Ejection Fraction

Circulation ◽

10.1161/circ.142.suppl_3.13570 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Katsuomi IWAKURA ◽

Toshinari Onishi ◽

Koichi Inoue ◽

Masato Okada ◽

Yasushi Koyama ◽

...

Keyword(s):

Heart Failure ◽

Body Weight ◽

Ejection Fraction ◽

Hospital Stay ◽

Diastolic Pressure ◽

Fluid Retention ◽

Repeated Measure ◽

Diabetic Patients ◽

Preserved Ejection Fraction ◽

Patients With Heart Failure

Introduction: Diabetes is observed in about third of patients with heart failure with preserved ejection fraction (HFpEF), and it is not well elucidated how it would affect the clinical conditions of HFpEF. We investigated the physical and echocardiographic characteristics of diabetes patients in a large-scale, registration study of HFpEF. Methods: We analyzed clinical and echocardiography data obtained at admission and just before hospital discharge in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction), which is a multicenter registration study of patients who were hospitalized for HFpEF. Results: We enrolled 862 patients who were hospitalized for HFpEF between June, 2016 and December, 2019 (Age 81±9 years, male gender 44.5%) for the present study. Diabetes was observed in 287 patients (33.3%), and their age was higher (82±8 years vs. 80±9 years, p=0.003) and body mass index before discharge was larger (23.2±4.7 kg/m2 vs. 21.1±4.6 kg/m2, p<0.0001) than those without diabetes. Diabetic patients had higher body weight at admission (63.2±14.9 kg vs. 55.9±13.4 kg, p<0.0001) and before discharge (56.8±13.3 vs. 50.7±12.1 kg, p<0.0001) than non-diabetic patients. Reduction of body weight during hospital stay was higher in diabetic patients (6.4±4.5 kg) than in non-diabetic patients (5.2±4.0 kg) even after correction of body weight discharge or estimated GFR (p<0.001 by ANCOVA). Body weight reduction was significantly associated with HbA1c (p=0.01). There was no difference in use of intravenous diuretics (69.3% vs. 66.6%, p=0.44) and in hospital stay (21.4±15.3 days vs. 19.9±13.7 days, p=0.14) between diabetic- and non-diabetic patients. Whereas no differences were observed in echocardiographic parameters at admission and before discharge between two arms, the diabetic arm showed significantly higher reduction in septal E/e’ ratio during hospital stay (19.0±8.7 to 17.1±7.6) than non-diabetic arm (16.6±8.3 to 16.4±8.2)(p=0.01 by repeated measure ANOVA). Conclusions: The present study implied that diabetic patients with HFpEF have more fluid retention before hospitalization than non-diabetic ones, which could affect the changes in diastolic pressure.

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The controlling nutritional status score predicts outcomes of cardiovascular events in patients with heart failure with preserved ejection fraction

IJC Heart & Vasculature ◽

10.1016/j.ijcha.2020.100563 ◽

2020 ◽

Vol 29 ◽

pp. 100563

Author(s):

Takashi Komorita ◽

Eiichiro Yamamoto ◽

Daisuke Sueta ◽

Takanori Tokitsu ◽

Koichiro Fujisue ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Nutritional Status ◽

Cardiovascular Events ◽

Preserved Ejection Fraction ◽

Status Score ◽

Patients With Heart Failure

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P6522Prognostic value of st2 in diabetic patients with heart failure and preserved ejection fraction

European Heart Journal ◽

10.1093/eurheartj/ehy566.p6522 ◽

2018 ◽

Vol 39 (suppl_1) ◽

Author(s):

O Medentseva ◽

I S Rudyk ◽

M M Udovychenko ◽

I G Kravchenko ◽

S N Pivovar ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Diabetic Patients ◽

Preserved Ejection Fraction ◽

Patients With Heart Failure

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P322Inhibitors of the renin-angiotensin system in diabetic patients with heart failure with preserved ejection fraction treatment: impact of m235t polymorphism of angiotensinogen

European Heart Journal ◽

10.1093/eurheartj/ehz747.0157 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

O Medentseva ◽

I S Rudyk ◽

M M Udovychenko ◽

I C Gasanov ◽

D P Babichev ◽

...

Keyword(s):

Heart Failure ◽

Blood Pressure ◽

Ejection Fraction ◽

Renin Angiotensin System ◽

Diabetic Patients ◽

Preserved Ejection Fraction ◽

Angiotensin System ◽

Patients With Heart Failure ◽

Heart Failure Questionnaire ◽

M235t Polymorphism

Abstract Background Inhibitors of the renin-angiotensin system plays an important role in chronic heart failure treatment. However, the impact of Angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II receptor blockers (ARBs) on treatment efficacy in diabetic patients with heart failure with preserved preserved ejection fraction (HFpEF) depending on M235T polymorphism of ATG is still unknown. Aim To estimate the efficacy of ACE inhibitors and ARBs therapy in diabetic patient with HFpEF depending on the polymorphism of the M235T of the ATG gene. Methods A total of eighty-two patients (50 females and 32 males; mean age 62,9±8,1 years) with HFpEF and type 2 diabetes mellitus were examined. Sixty-two patients were carriers of 235T allele (MT+TT genotypes), 20 patients had MM genotype of M235T polymorphism of ATG, which was determined by using of polymerase chain reaction. All patients were divided into 4 groups depending on genotypes taking Ramipril or Valsartan during 12 months. Clinical examination, 6 minute walking test, Minnesota Living with Heart Failure Questionnaire (MLHFQ) have been used. All statistical tests were 2-tailed and p<0,05 was considered statistically significant and performed in Statistica 10.0. Results It was not found the significant difference in efficacy of treatment using Valsartan or Ramipril in diabetic patients with genotype MM with HFpEF, whereas in the presence of the T allele of the polymorphism of the M235T ATG, use of valsartan was more effective. Table shows the dynamics of the investigated parameters. Dynamics of parametrs during treatment Parameters HFpEF and DM2T, TT or MT HFpEF and DM2T, MM Ramipril (n=22) Valsartan (n=21) Ramipril (n=10) Valsartan (n=10) Baseline After 12 months treatment Baseline After 12 months treatment Baseline After 12 months treatment Baseline After 12 months treatment SBP, mm Hg 172.0 [157.2; 178.5] 150.0 [132.0; 152.0]* 165.0 [145.3; 174.2] 128.0 [126.0; 134.0]* 167,5 [152.5; 176.0] 140.0 [134.0; 142.0] 160,0 [144.0; 170.0] 146.0 [138.0; 150.0] DBP, mm Hg 98.0 [86.0; 104.0] 92.0 [80.0; 94.0]* 96.0 [82.0; 100.0] 86.0 [80.0; 88.0]* 102.0 [84.0; 106.0] 98.0 [84.0; 100.0] 99.0 [80.0; 100.0] 94.0 [80.0; 96.0] 6 min test, m 313,0 [226,7; 375,5] 320,0 [236,4; 384,6]* 342.5 [258.0; 393.7] 372,0 [262,7; 397,9]* 305.0 [190.5; 375.0] 315.0 [198.5; 384.0] 328.0 [295.0; 401.0] 342.0 [298.0; 410.0] MLHFQ 62,0 [50,0; 71,2] 56,0 [46,5; 68,4]* 61.5 [50.5; 71.5] 40.5 [36.5; 56.5]* 60.0 [47.0; 76.2] 54.0 [43.0; 70.0] 58.0 [49.5; 76.2] 58.0 [49.5; 76.2] Dispnea, % 100 90* 100 70* 100 90 100 80 Edema, % 68,1 54,5* 61,9 33,3* 50 40 60 60 SBP, systolic blood pressure; DBP, diastolic blood pressure; MLHFQ, Minnesota Living with Heart Failure Questionnaire; statistically significant changes (p<0.05). Conclusion Use of Valsartan comparing to Ramipril in diabetic T allele carriers of M235T polymorphism of ATG with HFpEF was independently associated with more effective clinical signs of heart failure improvement, blood pressure decrease, quality of life according to the MLHFQ and physical activity tolerance increase.

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The impact of frailty and aging on prognosis in patients with heart failure with preserved ejection fraction – insights from PURSUIT-HFpEF registry

European Heart Journal ◽

10.1093/ehjci/ehaa946.0961 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Okada ◽

K Inoue ◽

T Onishi ◽

K Iwakura ◽

T Yamada ◽

...

Keyword(s):

Heart Failure ◽

Confidence Interval ◽

Ejection Fraction ◽

Hazard Ratio ◽

Adverse Outcomes ◽

Funding Source ◽

Preserved Ejection Fraction ◽

Clinical Endpoint ◽

Patients With Heart Failure

Abstract Introduction Frailty and aging are two common conditions both associated with increased vulnerability to stressful events with high risk of adverse outcomes. Purpose To evaluate the association between frailty and aging and their impacts on clinical outcome in patients with heart failure with preserved ejection fraction (HFpEF). Methods Analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 757 patients hospitalized for acute heart failure (diagnosed by using Framingham criteria) met the inclusion criteria: a left ventricular ejection fraction ≥50% and brain natriuretic peptide ≥100pg/ml. We included 483 patients (age, 80±9 years; men, 45%; atrial fibrillation, 35%) whose follow-up data after survival discharge were available. Patients' frailty and aging were evaluated using the clinical frailty scale (CFS) and age quartiles (Q1: <76 years (n=122), Q2: 76–82 years (n=111), Q3: 82–87 years (n=127), Q4: >87 years (n=123)), respectively. The primary clinical endpoint was defined as the composite of death, re-hospitalization for heart failure, and cerebrovascular accident. Results The median (interquartile range) CFS rating was 3 (2–5), and there was a little correlation between CFS rating and age (r2=0.16, p<0.001). The prevalence of frailty, defined as a CFS rating >4 (n=132), was positively correlated with age quartiles (Q1: 9.0%, Q2: 21.4%, Q3: 29.9%, Q4: 48.0%, p<0.001). During the median follow-up period 396 days (interquartile range, 344–698) after discharge, the clinical endpoint was observed in 172 patients. The incidence was higher in patients with frailty than those without it (49.6% vs. 30.4%, log-rank p<0.001). It was also correlated with age quartiles (Q1: 23.0%, Q2: 34.2%, Q3: 36.2%, Q4: 48.8%, log-rank p=0.001). Multivariate Cox regression analysis revealed that frailty (hazard ratio, 1.52; 95% confidence interval, 1.09–2.10; p=0.013) and age (hazard ratio per quartile increase, 1.24; 95% confidence interval, 1.07–1.43; p=0.004) were both associated with the clinical endpoint. Subgroup analysis in 352 patients without frailty also revealed the significant impact of age on the endpoint (1.26; 1.06–1.51; p=0.008). However, in 131 patients with frailty, there was no significant impact of age on the endpoint (1.16; 0.90–1.51; p=0.25). Conclusions Frailty was common and was associated with aging in HFpEF patients. Although they were both associated with unfavorable events, aging was no longer a significant predictor of adverse outcomes under the frailty conditions. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K. and Fuji Film Toyama Chemical Co. Ltd.

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