The Predictive Effect Of CHA₂DS₂-VASC Score On All-cause Mortality In Patients With Heart Failure And Its Comparison With BNP And NT-proBNP

Part1:Prognostic Value of CHA₂DS₂-VASC Score for All-cause Mortality in Heart Failure Patients with Reduced,Mid-Range,and Preserved Ejection Fraction,with and without Atrial FibrillationBackgroundHeart failure（HF）is the end stage of various cardiac diseases.With increasing incidence and prevalence,high re-hospitalization and mortality1 among the elderly,HF has become a significant public health problem.In recent years,cardiac natriuretic peptides have been recognized as diagnostic and prognostic biomarkers of heart failure（HF）,and have been routinely used in clinical practice.However,there are still some limits for their clinical utilization,such as invasiveness,high price and various influence factors.It indicated that there is a need for easier and better assessment tools for risk stratification of mortality in HF patientsAs a simple and useful tool,CHA₂DS₂-VASC[congestive HF,hypertension,age>75 （doubled）,diabetes,stroke（doubled）,vascular disease,age 65-74,and sex category（female）]has been recommended for prediction of stroke risk in patients with non-valvular atrial fibrillation（AF）.A few recent studies have shown a certain correlation between CHA₂DS₂-VASC score（CHA₂DS₂-VASCs）and long-term mortality risk in patients with HF.However,most current data are about HF with reduced ejection fraction（HFrEF）,the relations between CHA₂DS₂-VASCs and HF patients with mid-range（HFmrEF）or preserved ejection fraction（HFpEF）are still less well known,and it remains unclear whether CHA₂DS₂-VASCs has prognostic value for risk stratification of mortality in patients with HFmrEF and HFpEF.Since CHA₂DS₂-VASCs was originally recommended for prediction of stroke risk in patients with atrial fibrillation,it is rational and imperative to take account of AF when investigating its prognostic value in HF patients.The purpose of this study was to investigate the prognostic value of CHA₂DS₂-VASCs for risk stratification of long-term mortality in heart failure patients with HFrEF,HFmrEF and HFpEF,and assess the impact of AF on its prognostic effectiveness in all 3-EF groups.Aim:To investigate the prognostic value of CHA₂DS₂-VASC score（CHA₂DS₂-VASCs）for risk stratification of mortality in heart failure patients with reduced（HFrEF）,mid-range（HFmrEF）,and preserved ejection fraction（HFpEF）,and assess the impact of atrial fibrillation on its prognostic effectiveness in patients with different phenotypes of left ventricular ejection fraction（LVEF）.Methods:The study consecutively enrolled patients hospitalized for acute or decompensate chronic HF across the full spectrum of left ventricular ejection fraction（LVEF）in HF center,FuWai Hospital,Beijing（China）from January 2013 to July 2017.Patients were enrolled if they were（1）between 18 and 85 years of age（2）with typical signs and symptoms of HF and New York Heart Association（NYHA）functional classification Ⅱto IV（3）with structural abnormalities documented by echocardiograms;（4）having data for rhythm（according to electrocardiography,or 24 hour ambulatory electrocardiogram）（4）having venous blood sample available for analysis（5）having written informed consents.Patients were excluded from this analysis if they were（1）with acute coronary syndrome;（2）with acute pulmonary embolism;（3）with cancer,amyloid cardiomyopathy or valvular disease requiring surgical intervention;（4）end with heart transplants;（5）who refused to sign informed consents.According to their CHA₂DS₂-VASCs,patients were givenl point respectively if they were with hospitalization for HF,hypertension,age 65 to74 years,diabetes mellitus,vascular disease,and female sex,and the ones were given 2 points respectively if they were with previous stroke or age 75 years or older.The CHA₂DS₂-VASCs was calculated regardless of the presence of AF or not.Based on CHA₂DS₂-VASCs,patients were stratified into 3 groups:0 to 3（low score）,4 to 6（intermediate score）,and7 to 9（high score）.Based on 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure,we defined HFrEF,HFmrEF and HFpEF as LVEF<40%,LVEF between40%-50%,and LVEF ≥ 50%.We divided the subjects into AF group or non-AF group according to the presence or absence of AF at the time of hospitalization or medical history,and the data of electrocardiography or 24 hour ambulatory electrocardiogram.The follow-up started on the day of discharge.All-cause death was ascertained by electronic hospital records,telephone interviews,and patients’ regular visits to physician outpatient clinics.ResultsDistribution and frequency of CHA₂DS₂-VASCs differed among 3EF-groups,and patients with HFmrEF and HFpEF had higher scores than those with HFrEF.CHA₂DS₂-VASC scores of 3EF-groups were 4（2-5）,3（2-5）and 3（2-4）,respectively.Compared with HFrEF（32.6%）or HFmrEF（37.7%）,the HFpEF subgroup had more AF patients（56.9%）.Patients with atrial fibrillation in all 3-ef groups had higher CHA₂DS₂-VASC scores than those without AF.CHA₂DS₂-VASCs>3 was an independent risk factor of all-cause death in patients with HFpEF,HFmrEF,and HFrEF,even after adjusting for other confounding factors.CHA₂DS₂-VASCs had slight prognostic value for long-term all-cause death in HFrEF group and modest prognostic value in HFmrEF,and HFpEF groups,the AUCs were 0.583（0.526-0.608,p=0.0113）,0.637（0.563-0.707,p=0.0037）,0.625（0.572-0.677,p =0.0002）,respectively.Besides,CHA₂DS₂-VASCs had better performance in predicting mortality in patients with sinus rhythm than the ones with AF,when the ejection fraction is reduced or preserved,however,the result was opposite in HFmrEF.Conclusion:CHA₂DS₂-VASCs had modest prognostic value in HFmrEF,and HFpEF groups and only slight prognostic value for long-term all-cause death in HFrEF group.In addition,AF might be a considerable factor to affect the prognostic value of CHA₂DS₂-VASCs in patients with different phenotypes of LVEF.Part 2:Associations between Atrial Fibrillation and NT-proBNP,BNP of Heart Failure Patients with Reduced or Preserved Ejection FractionBackground:Atrial fibrillation is the most common arrhythmia in clinical practice,and it is associated with poor prognosis of patients,such as death and stroke.20-40%of patients with heart failure combined with atrial fibrillation.Brain natriuretic peptide（BNP）and amino terminal brain natriuretic peptide（NT-proBNP）are markers for diagnostic and prognostic of heart failure and have been widely used in clinical practice.The level of nt-probnp/BNP level and other factors that affect the level of nt-probnp/BNP should be further explored when the patients with different ejection fractions（EF）,with atrial fibrillation and without atrial fibrillation.Background:Atrial fibrillation is the most common arrhythmia in clinical practice,and it is associated with poor prognosis of patients,such as death and stroke.20-40%of patients with heart failure combined with atrial fibrillation.Brain natriuretic peptide（BNP）and amino terminal brain natriuretic peptide（NT-proBNP）are markers for diagnostic and prognostic of heart failure and have been widely used in clinical practice.The level of nt-probnp/BNP level and other factors that affect the level of nt-probnp/BNP should be further explored when the patients with different ejection fractions（EF）,with atrial fibrillation and without atrial fibrillation.Aims:The study focus on the associations between atrial fibrillation（AF）and the concentrations of NT-proBNP and BNP in heart failure patients with reduced（HFrEF）and preserved ejection fraction（HFpEF）.Methods:The study included 529 hospitalized patients with heart failure during January 2015 and September 2016,their information and materials were collected,the concentrations of NT-proBNP and BNP were tested on admission.AF was ascertained according to their medical history,the results of electrocardiogram and dynamic electrocardiogram examination.Paroxysmal AF and persistent AF were denied as AF with duration less than 7 day or AF with duration more than 7 day.Results:Both in HFrEF and HFpEF groups,the concentrations of NT-proBNP of patients with AF were higher than the ones without AF（1993～10896 vs 932～6345 pg/ml,P=0.014,and 1154～4945 vs 521～5491 pg/ml,P=0.032）,while there was no statistically significant difference between their BNP concentrations（245～1005/182～1165 pg/ml,P=0.778,and 209～643 vs 97～643 pg/ml,P=0.313）.The two biomarkers had less influence factors in patients with AF than in ones without AF.In HFrEF group,concentration of BNP was significantly associated with BMI,NYHA heart function classification,left ventricular end-diastolic diameter;concentration of NT-proBNP was significantly associated with age,BMI,NYHA heart function classification,left ventricular end-diastolic diameter,serum creatinine,blood urea nitrogen.In HFpEF group,concentration of BNP was significantly associated with the use of ACEI,serum creatinine;concentration of NT-proBNP was significantly associated with the use of ACEI,anticoagulant drugs and pulmonary artery pressure.Conclusion:Both in HFrEF and HFpEF groups,the concentrations of NT-proBNP of patients with AF were higher than that of patients without AF.AF and its type had little effect on concentration of BNP.The patients with AF had less influence factors of NT-proBNP and BNP than the ones without AF.Part3:The Predictive Values of BNP,NT-proBNP and CHA2DS2-VASc Score for All-cause Mortality in Patients withHeart FailureBackground:The evaluation of prognosis in patients with heart failure is helpful for patients,their families and clinical doctors making wise decisions in timely and proper treatment,including instrument treatment,disease monitoring,heart transplantation or end-of-life care.B-type natriuretic peptide（BNP）and N-terminal b-type natriuretic peptide（NT-proBNP）are biomarkers which have been widely used to evaluate the prognosis of patients with heart failure in clinical practice.At present,the researches about relationship between the prognosis of NT-proBNP and prognosis of heart failure only paid attention to study population with reduced or preserved ejection fraction.The results of our first part show that CHA₂DS₂-VASC score has a certain predictive value for all-cause mortality in patients with reduced、medium-range or preserved ejection fraction.Since CHA2DS2-VASc score was recommended for prediction of stroke risk in patients with non-valvular atrial fibrillation,it is rational and imperative to take account of AF when investigating its prognostic value in HF patients.Aims:This study compared the predictive value of BNP,NT-proBNP,CHA2DS2 VASC score for all-cause mortality in patients with reduced,medium-range or preserved ejection fraction,with or without atrial fibrillation.Methods:This study included hospitalized patients with heart failure during January 2013 and July 2017.Their medical records were collected,and serum concentrations of BNP and NT-proBNP were tested.Based on 2016 ESC in the diagnosis and treatment of acute and chronic heart failure guidelines,heart failure patients with reduced ejection fraction,medium-range ejection fraction and preserved ejection fraction were defined as left ventricular ejection fraction<40%,40%to 50%,and>50%,respectively.According to their CHA2DS2-VASc score,patients were given1 point respectively,if they were with hospitalization for HF,hypertension,age 65 to74 years,diabetes mellitus,vascular disease,and female sex,and the ones were given 2 points respectively if they were with previous stroke or age 75 years or older.The CHA2DS2-VASc score was calculated regardless of the presence of AF or not.The patient was diagnosed with atrial fibrillation according to his medical history,electrocardiogram and 24-hour dynamic electrocardiogram.Then the correlation between BNP,NT-proBNP CHA2DS2-VASc score and all-cause mortality was evaluated.The follow-up started on the day of discharge.All-cause death was ascertained by electronic hospital records,telephone interviews,and patients’ regular visits to outpatient clinics.Results:CHA2DS2-VASc score of patients with heart failure with atrial fibrillation was higher than that of patients without atrial fibrillation.The percentages of patients with atrial fibrillation scored between 4-6 and scores>9 were 46.9%and 37.4%,respectively,There was no significant difference between BNP levels of patients with atrial fibrillation and without atrial fibrillation group,while the concentration of NT-proBNP of patients with atrial fibrillation was higher than that of patients without atrial fibrillation,respectively 2660（1144-6416）pg/ml and 2313（772-5780）pg/ml,P=0.027.In all patients with heart failure,both of NT-proBNP and CHA2DS2 VASC score had predictive effects on all-cause mortality.The AUC of BNP,NT-proBNP and CHA2DS2-VASc score were 0.536（95%CI:0.502-0.569,P=0.105）,0.683（95%CI:0.651-0.713,P<0.001）and 0.5860（95%CI:0.553-0.619,P<0.001）.NT-proBNP had the highest predictive value,CHA2DS2-VASc score,predictive value of the BNP was weakest.For patients with heart failure who did not combine atrial fibrillation,the predictive value of NT-proBNP was the highest,and CHA2DS2-VASc score was the second,and BNP had the worst predictive value.For patients with heart failure combined with atrial fibrillation,only NT-proBNP had predictive value.The NT-proBNP and CHA2DS2-VASc score had predictive effect on all ejection fraction subgroup,and the BNP only had predictive value for the heart failure patients with preserved ejection fraction.Conclusion:According to the presence of atrial fibrillation or not,NT-proBNP had predictive effects on both atrial fibrillation group and non-atrial fibrillation group.CHA2DS2-VASc score was only a predictor of mortality in patients without atrial fibrillation,According to the different ejection fraction phenotype,both of NT-pro BNP and CHA2DS2-VASc score could be used to predict all-cause mortality in heart failure patients with reduced,medium-range or preserved ejection fraction,NT-pro BNP had better predictive value than CHA2DS2-VASc score,while BNP only had predictive value in heart failure patients with preserved ejection fraction.