Objective To investigate prognostic predictors of long-term survival of patients with cardiac amyloidosis (CA), and to determine predictive value of high-sensitivity cardiac troponin T (hs-cTnT) in CA patients. Me...Objective To investigate prognostic predictors of long-term survival of patients with cardiac amyloidosis (CA), and to determine predictive value of high-sensitivity cardiac troponin T (hs-cTnT) in CA patients. Methods We recruited 102 consecutive CA cases and followed these patients for 5 years. We described their clinical characteristics at presentation and used a new, high-sensitivity assay to determine the concentration of cTnT in plasma samples from these patients. Results The patients with poor prognosis showed older age (56 ±12 years vs. 50 ±15 years, P=0.022), higher incidences of heart failure (36.92%vs. 16.22%, P=0.041), pericardial effusion (60.00%vs. 35.14%, P=0.023), greater thickness of interventricular septum (IVS) (15 ±4 mm vs. 13 ±4 mm, P=0.034), higher level of hs-cTnT (0.186 ±0.249 ng/mL vs. 0.044 ±0.055 ng/mL, P=0.001) and higher NT-proBNP (N-terminal pro-B-type natriuretic pep-tide) levels (11,742 ± 10,464 pg/mL vs. 6,031 ± 7,458 pg/mL, P=0.006). At multivariate Cox regression analysis, heart failure (HR:1.78, 95%CI:1.09-2.92, P=0.021), greater wall thickness of IVS (HR:1.44, 95%CI:1.04-3.01, P=0.0375) and higher hs-cTnT level (HR:6.16, 95%CI:2.20-17.24, P=0.001) at enrollment emerged as independent predictors of all-cause mortality. Conclusions We showed that hs-cTnT is associated with a very ominous prognosis, and it is also the strongest predictor of all-cause mortality in multivariate analysis. Examination of hs-cTnT concentrations provides valuable prognostic information concerning long-term outcomes.展开更多
High-sensitivity cardiac troponin(hs-cTn) assays are increasingly being used in many countries worldwide,however,a generally accepted definition of high-sen-sitivity is still pending.These assays enable cTn mea-sureme...High-sensitivity cardiac troponin(hs-cTn) assays are increasingly being used in many countries worldwide,however,a generally accepted definition of high-sen-sitivity is still pending.These assays enable cTn mea-surement with a high degree of analytical sensitivity with a low analytical imprecision at the low measuring range of cTn assays(coefficient of variation of < 10% at the 99th percentile upper reference limit).One of the most important advantages of these new assays is that they allow novel,more rapid approaches to rule in or rule out acute coronary syndromes(ACSs) than with previous cTn assay generations which are still more commonly used in practice worldwide.hs-cTn is also more sensitive for the detection of myocardial damage unrelated to acute myocardial ischemia.Therefore,the increase in early diagnostic sensitivity of hs-cTn assays for ACS comes at the cost of a reduced ACS specificity,because more patients with other causes of acute or chronic myocardial injury without overt myocardial isch-emia are detected than with previous cTn assays.As hs-cTn assays are increasingly being adopted in clinical practice and more hs-cTn assays are being developed,this review attempts to synthesize the available clinical data to make recommendations for their everyday clini-cal routine use.展开更多
Background N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are excellent biomarkers for detecting heart failure and subclinical myocardial injury.However,it ...Background N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are excellent biomarkers for detecting heart failure and subclinical myocardial injury.However,it remains unclear whether subclinical myocardial injury is associated with NT-proBNP elevation in a community based population.Methods In a community based study,levels of hs-cTnT and of NT-proBNP were determined in 1 497 participants older than 45 years.The lower detection limit of the hs-cTnT assay used in the present study was 0.003 ng/ml.The association of hs-cTnT levels and NT-proBNP levels was analyzed.Results When the subjects with undetectable (〈0.003 ng/ml),intermediate (0.003-0.014 ng/ml),and elevated (≥0.014 ng/ml) levels of hs-cTnT were compared (r=0.175,P 〈0.001),a strong association between the hs-cTnT levels and NT-proBNP levels was observed (β=-0.206,P 〈0.001; β=-0.118,P 〈0.001,respectively).In multivariable analyses,older age and hs-cTnT were positively and independently associated with NT-proBNP levels (β=0.341,P 〈0.001; β=0.143,P 〈0.001,respectively),and male gender and the levels of eGFR were inversely and independently associated with NT-proBNP levels.When the subjects with normal or elevated NT-proBNP were analyzed separately,the hs-cTnT level was not an independent predictor for the NT-proBNP level in the normal NT-proBNP group,whereas the hs-cTnT level was the only independent predictor for NT-proBNP level in the elevated NT-proBNP group (β=0.399,P 〈0.01).Conclusions In this community based population,NT-proBNP elevation was common.In addition to female gender and older age,subclinical myocardial injury indicated by the hs-cTnT level was another important factor in NT-proBNP elevation.展开更多
BACKGROUND:Early reperfusion can effectively treat acute myocardial infarction(AMI) and reduce the mortality signif icantly. This study aimed to compare the role of plasma microRNA-1(miR-1) and cardiac troponin T(cTnT...BACKGROUND:Early reperfusion can effectively treat acute myocardial infarction(AMI) and reduce the mortality signif icantly. This study aimed to compare the role of plasma microRNA-1(miR-1) and cardiac troponin T(cTnT) in early diagnosis of AMI patients.METHODS:From May 2011 to May 2012,plasma samples were collected from 56 AMI patients and 28 non-AMI controls. The expression of plasma miR-1 was measured by quantitative reverse transcription-polymerase chain reaction(qRT-PCR),and the level of plasma cTnT was measured using electrochemiluminescence-based methods on an Elecsys 2010 Immunoassay Analyzer. SPSS 16.0 was used for the statistical analysis of the results. Data were expressed as mean±standard deviation unless otherwise described. The differences about clinical characteristics between the AMI patients and controls were tested using Student's t test or Fisher's exact test. The Mann-Whitney U test was conducted to compare the expression of microRNAs between the AMI patients and controls. MicroRNAs expression between different intervals of the AMI patients was compared using Wilcoxon's signed-rank test. The receiver operating characteristic(ROC) curve was established to discriminate the AMI patients from the controls.RESULTS:In the present study,the expression of plasma miR-1 was signifi cantly increased in the AMI patients compared with the healthy controls(P<0.01). The plasma miR-1 in the AMI patients decreased to the normal level at 14 days(P>0.05). The expression of plasma miR-1 was not related to the clinical characteristics of the study population(P>0.05). ROC curve analyses demonstrated that miR-1 was specifi c and sensitive for the early diagnosis of AMI,but not superior to cTnT.CONCLUSION:Plasma miR-1 could be used in the early diagnosis of AMI,but it is similar to cTnT.展开更多
Sensitive detection and precise quantitation of trace-level crucial biomarkers in a complex sample matrix has become an important area of research.For example,the detection of high-sensitivity cardiac troponin I (hs-c...Sensitive detection and precise quantitation of trace-level crucial biomarkers in a complex sample matrix has become an important area of research.For example,the detection of high-sensitivity cardiac troponin I (hs-cTnI) is strongly recommended in clinical guidelines for early diagnosis of acute myocardial infarction.Based on the use of an electrode modified by single-walled carbon nanotubes (SWCNTs) and a Ru(bpy)32+-doped silica nanoparticle (Ru@SiO2)/tripropylamine (TPA) system,a novel type of electrochemiluminescent (ECL) magnetoimmunosensor is developed for ultrasensitive detection of hs-cTnI.In this approach,a large amount of[Ru(bpy)3]2+is loaded in SiO2(silica nanoparticles) as luminophores with high luminescent efficiency and SWCNTs as electrode surface modification material with excellent electrooxidation ability for TPA.Subsequently,a hierarchical micropillar array of microstructures is fabricated with a magnet placed at each end to efficiently confine a single layer of immunomagnetic microbeads on the surface of the electrode and enable 7.5-fold signal enhancement In particular,the use of transparent SWCNTs to modify a transparent ITO electrode provides a two-order-of-magnitude ECL signal amplification.A good linear calibration curve is developed for hs-cTnI concentrations over a wide range from 10 fg/ml to 10 ng/ml,with the limit of detection calculated as 8.720 fg/ml (S/N=3).This ultrasensitive immunosensor exhibits superior detection performance with remarkable stability,reproducibility,and selectivity.Satisfactory recoveries are obtained in the detection of hs-cTnI in human serum,providing a potentia analysis protocol for clinical applications.展开更多
BACKGROUND Cardiac involvement in neonates with perinatal asphyxia not only complicates perinatal management but also contributes to increased mortality.AIM To assess cardiac troponin T(cTnT)levels in asphyxiated neon...BACKGROUND Cardiac involvement in neonates with perinatal asphyxia not only complicates perinatal management but also contributes to increased mortality.AIM To assess cardiac troponin T(cTnT)levels in asphyxiated neonates and their correlation with echocardiography findings,inotrope requirement,hypoxicischemic encephalopathy(HIE)stages,and mortality.METHODS cTnT levels,echocardiographic findings,the requirement of inotropes,HIE stages,and outcome were studied in neonates of gestational age≥34 wk with perinatal asphyxia.RESULTS Among 57 neonates with perinatal asphyxia,male gender,cesarean section,forceps/vacuum-assisted vaginal delivery and late preterm included 33(57.9%),23(40.4%),3(5.3%),and 12(21.1%)respectively.The mean gestational age was 38.4 wk(1.6 wk).HIE stages I,II,and III were observed in 7(12.3%),37(64.9%),and 9(15.8%)neonates respectively.26(45.6%)neonates had echocardiographic changes and 19(33.3%)required inotropes.cTnT levels were elevated in 41(71.9%)neonates[median(IQR);0.285(0.211-0.422)ng/mL].The Median cTnT level showed an increasing trend with increasing changes in echocardiography(P=0.002).Two neonates with mitral regurgitation and global hypokinesia had the highest cTnT levels(1.99 and 0.651 ng/mL).Of 31 neonates with normal echocardiography,18(58.06%)showed elevated cTnT.cTnT levels were significantly higher in those who required inotropic support than those who did not(P=0.007).Neonates with HIE stage III had significantly higher cTnT levels compared to those with HIE stage I/II(P=0.013).Survivors had lower median cTnT levels[0.210(0.122-0.316)ng/mL]than who succumbed[0.597(0.356-1.146)ng/mL].CONCLUSION cTnT levels suggestive of cardiac involvement were observed in 71.9%of asphyxiated neonates.cTnT levels correlated with echocardiography findings,inotrope requirement,HIE stages,and mortality.展开更多
Background:The relationship between the elevation of cardiac troponin and the increase of mortality and hospitalization rate in patients with heart failure with reduced ejection fraction is clear.This study investigat...Background:The relationship between the elevation of cardiac troponin and the increase of mortality and hospitalization rate in patients with heart failure with reduced ejection fraction is clear.This study investigated the association between the extent of elevated levels of high-sensitivity cardiac troponin I(hs-cTnI)and the prognosis in heart failure with preserved ejection fraction patients.Methods:A retrospective cohort study consecutively enrolled 470 patients with heart failure with preserved ejection fraction from September 2014 to August 2017.According to the level of hs-cTnI,the patients were divided into the elevated level group(hs-cTnI>0.034 ng/mL in male and hs-cTnI>0.016 ng/mL in female)and the normal level group.All of the patients were followed up once every 6 months.Adverse cardiovascular events were cardiogenic death and heart failure hospitalization.Results:The mean follow-up period was 36.2±7.9 months.Cardiogenic mortality(18.6%[26/140]vs.1.5%[5/330],P<0.001)and heart failure(HF)hospitalization rate(74.3%[104/140]vs.43.6%[144/330],P<0.001)were significantly higher in the elevated level group.The Cox regression analysis showed that the elevated level of hs-cTnI was a predictor of cardiogenic death(hazard ratio[HR]:5.578,95%confidence interval[CI]:2.995-10.386,P<0.001)and HF hospitalization(HR:3.254,95%CI:2.698-3.923,P<0.001).The receiver operating characteristic curve demonstrated that a sensitivity of 72.6%and specificity of 88.8%for correct prediction of adverse cardiovascular events when a level of hs-cTnI of 0.1305 ng/mL in male and a sensitivity of 70.6%and specificity of 90.2%when a level of hs-cTnI of 0.0755 ng/mL in female were used as the cut-off value.Conclusion:Significant elevation of hs-cTnI(≥0.1305 ng/mL in male and≥0.0755 ng/mL in female)is an effective indicator of the increased risk of cardiogenic death and HF hospitalization in heart failure with preserved ejection fraction patients.展开更多
文摘Objective To investigate prognostic predictors of long-term survival of patients with cardiac amyloidosis (CA), and to determine predictive value of high-sensitivity cardiac troponin T (hs-cTnT) in CA patients. Methods We recruited 102 consecutive CA cases and followed these patients for 5 years. We described their clinical characteristics at presentation and used a new, high-sensitivity assay to determine the concentration of cTnT in plasma samples from these patients. Results The patients with poor prognosis showed older age (56 ±12 years vs. 50 ±15 years, P=0.022), higher incidences of heart failure (36.92%vs. 16.22%, P=0.041), pericardial effusion (60.00%vs. 35.14%, P=0.023), greater thickness of interventricular septum (IVS) (15 ±4 mm vs. 13 ±4 mm, P=0.034), higher level of hs-cTnT (0.186 ±0.249 ng/mL vs. 0.044 ±0.055 ng/mL, P=0.001) and higher NT-proBNP (N-terminal pro-B-type natriuretic pep-tide) levels (11,742 ± 10,464 pg/mL vs. 6,031 ± 7,458 pg/mL, P=0.006). At multivariate Cox regression analysis, heart failure (HR:1.78, 95%CI:1.09-2.92, P=0.021), greater wall thickness of IVS (HR:1.44, 95%CI:1.04-3.01, P=0.0375) and higher hs-cTnT level (HR:6.16, 95%CI:2.20-17.24, P=0.001) at enrollment emerged as independent predictors of all-cause mortality. Conclusions We showed that hs-cTnT is associated with a very ominous prognosis, and it is also the strongest predictor of all-cause mortality in multivariate analysis. Examination of hs-cTnT concentrations provides valuable prognostic information concerning long-term outcomes.
文摘High-sensitivity cardiac troponin(hs-cTn) assays are increasingly being used in many countries worldwide,however,a generally accepted definition of high-sen-sitivity is still pending.These assays enable cTn mea-surement with a high degree of analytical sensitivity with a low analytical imprecision at the low measuring range of cTn assays(coefficient of variation of < 10% at the 99th percentile upper reference limit).One of the most important advantages of these new assays is that they allow novel,more rapid approaches to rule in or rule out acute coronary syndromes(ACSs) than with previous cTn assay generations which are still more commonly used in practice worldwide.hs-cTn is also more sensitive for the detection of myocardial damage unrelated to acute myocardial ischemia.Therefore,the increase in early diagnostic sensitivity of hs-cTn assays for ACS comes at the cost of a reduced ACS specificity,because more patients with other causes of acute or chronic myocardial injury without overt myocardial isch-emia are detected than with previous cTn assays.As hs-cTn assays are increasingly being adopted in clinical practice and more hs-cTn assays are being developed,this review attempts to synthesize the available clinical data to make recommendations for their everyday clini-cal routine use.
基金This study was supported by grants from the National Basic Research Program of China,Nature Science Foundation of China
文摘Background N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are excellent biomarkers for detecting heart failure and subclinical myocardial injury.However,it remains unclear whether subclinical myocardial injury is associated with NT-proBNP elevation in a community based population.Methods In a community based study,levels of hs-cTnT and of NT-proBNP were determined in 1 497 participants older than 45 years.The lower detection limit of the hs-cTnT assay used in the present study was 0.003 ng/ml.The association of hs-cTnT levels and NT-proBNP levels was analyzed.Results When the subjects with undetectable (〈0.003 ng/ml),intermediate (0.003-0.014 ng/ml),and elevated (≥0.014 ng/ml) levels of hs-cTnT were compared (r=0.175,P 〈0.001),a strong association between the hs-cTnT levels and NT-proBNP levels was observed (β=-0.206,P 〈0.001; β=-0.118,P 〈0.001,respectively).In multivariable analyses,older age and hs-cTnT were positively and independently associated with NT-proBNP levels (β=0.341,P 〈0.001; β=0.143,P 〈0.001,respectively),and male gender and the levels of eGFR were inversely and independently associated with NT-proBNP levels.When the subjects with normal or elevated NT-proBNP were analyzed separately,the hs-cTnT level was not an independent predictor for the NT-proBNP level in the normal NT-proBNP group,whereas the hs-cTnT level was the only independent predictor for NT-proBNP level in the elevated NT-proBNP group (β=0.399,P 〈0.01).Conclusions In this community based population,NT-proBNP elevation was common.In addition to female gender and older age,subclinical myocardial injury indicated by the hs-cTnT level was another important factor in NT-proBNP elevation.
基金supported by grants from the National Natural Science Foundation of China(81071030)the Science and Technology Foundation of Guangdong Province(2011B080701006)
文摘BACKGROUND:Early reperfusion can effectively treat acute myocardial infarction(AMI) and reduce the mortality signif icantly. This study aimed to compare the role of plasma microRNA-1(miR-1) and cardiac troponin T(cTnT) in early diagnosis of AMI patients.METHODS:From May 2011 to May 2012,plasma samples were collected from 56 AMI patients and 28 non-AMI controls. The expression of plasma miR-1 was measured by quantitative reverse transcription-polymerase chain reaction(qRT-PCR),and the level of plasma cTnT was measured using electrochemiluminescence-based methods on an Elecsys 2010 Immunoassay Analyzer. SPSS 16.0 was used for the statistical analysis of the results. Data were expressed as mean±standard deviation unless otherwise described. The differences about clinical characteristics between the AMI patients and controls were tested using Student's t test or Fisher's exact test. The Mann-Whitney U test was conducted to compare the expression of microRNAs between the AMI patients and controls. MicroRNAs expression between different intervals of the AMI patients was compared using Wilcoxon's signed-rank test. The receiver operating characteristic(ROC) curve was established to discriminate the AMI patients from the controls.RESULTS:In the present study,the expression of plasma miR-1 was signifi cantly increased in the AMI patients compared with the healthy controls(P<0.01). The plasma miR-1 in the AMI patients decreased to the normal level at 14 days(P>0.05). The expression of plasma miR-1 was not related to the clinical characteristics of the study population(P>0.05). ROC curve analyses demonstrated that miR-1 was specifi c and sensitive for the early diagnosis of AMI,but not superior to cTnT.CONCLUSION:Plasma miR-1 could be used in the early diagnosis of AMI,but it is similar to cTnT.
基金The authors acknowledge financial support from the National Natural Science Foundation of China(Grant Nos.62001460,31971368,12202461,and 22104148)the Guangdong Regional Joint Funds for Young Scientists(Grant Nos.2020A1515110201 and 2020A1515110368)+2 种基金Guangdong Provincial General Funding(Grant No.2021A1515220156)Guangdong Basic and Applied Basic Research Funding-Regional Joint Fund(Grant No.2020B1515120040)Shenzhen Science and Technology Research Funding(Grant Nos.JSGG20201103153801005,JSGG20191115141601721,ZDSYS20220527171406014,JCYJ20220818101412027,JCYJ20200109115635440,and JCYJ 20200109115408041).
文摘Sensitive detection and precise quantitation of trace-level crucial biomarkers in a complex sample matrix has become an important area of research.For example,the detection of high-sensitivity cardiac troponin I (hs-cTnI) is strongly recommended in clinical guidelines for early diagnosis of acute myocardial infarction.Based on the use of an electrode modified by single-walled carbon nanotubes (SWCNTs) and a Ru(bpy)32+-doped silica nanoparticle (Ru@SiO2)/tripropylamine (TPA) system,a novel type of electrochemiluminescent (ECL) magnetoimmunosensor is developed for ultrasensitive detection of hs-cTnI.In this approach,a large amount of[Ru(bpy)3]2+is loaded in SiO2(silica nanoparticles) as luminophores with high luminescent efficiency and SWCNTs as electrode surface modification material with excellent electrooxidation ability for TPA.Subsequently,a hierarchical micropillar array of microstructures is fabricated with a magnet placed at each end to efficiently confine a single layer of immunomagnetic microbeads on the surface of the electrode and enable 7.5-fold signal enhancement In particular,the use of transparent SWCNTs to modify a transparent ITO electrode provides a two-order-of-magnitude ECL signal amplification.A good linear calibration curve is developed for hs-cTnI concentrations over a wide range from 10 fg/ml to 10 ng/ml,with the limit of detection calculated as 8.720 fg/ml (S/N=3).This ultrasensitive immunosensor exhibits superior detection performance with remarkable stability,reproducibility,and selectivity.Satisfactory recoveries are obtained in the detection of hs-cTnI in human serum,providing a potentia analysis protocol for clinical applications.
文摘BACKGROUND Cardiac involvement in neonates with perinatal asphyxia not only complicates perinatal management but also contributes to increased mortality.AIM To assess cardiac troponin T(cTnT)levels in asphyxiated neonates and their correlation with echocardiography findings,inotrope requirement,hypoxicischemic encephalopathy(HIE)stages,and mortality.METHODS cTnT levels,echocardiographic findings,the requirement of inotropes,HIE stages,and outcome were studied in neonates of gestational age≥34 wk with perinatal asphyxia.RESULTS Among 57 neonates with perinatal asphyxia,male gender,cesarean section,forceps/vacuum-assisted vaginal delivery and late preterm included 33(57.9%),23(40.4%),3(5.3%),and 12(21.1%)respectively.The mean gestational age was 38.4 wk(1.6 wk).HIE stages I,II,and III were observed in 7(12.3%),37(64.9%),and 9(15.8%)neonates respectively.26(45.6%)neonates had echocardiographic changes and 19(33.3%)required inotropes.cTnT levels were elevated in 41(71.9%)neonates[median(IQR);0.285(0.211-0.422)ng/mL].The Median cTnT level showed an increasing trend with increasing changes in echocardiography(P=0.002).Two neonates with mitral regurgitation and global hypokinesia had the highest cTnT levels(1.99 and 0.651 ng/mL).Of 31 neonates with normal echocardiography,18(58.06%)showed elevated cTnT.cTnT levels were significantly higher in those who required inotropic support than those who did not(P=0.007).Neonates with HIE stage III had significantly higher cTnT levels compared to those with HIE stage I/II(P=0.013).Survivors had lower median cTnT levels[0.210(0.122-0.316)ng/mL]than who succumbed[0.597(0.356-1.146)ng/mL].CONCLUSION cTnT levels suggestive of cardiac involvement were observed in 71.9%of asphyxiated neonates.cTnT levels correlated with echocardiography findings,inotrope requirement,HIE stages,and mortality.
文摘Background:The relationship between the elevation of cardiac troponin and the increase of mortality and hospitalization rate in patients with heart failure with reduced ejection fraction is clear.This study investigated the association between the extent of elevated levels of high-sensitivity cardiac troponin I(hs-cTnI)and the prognosis in heart failure with preserved ejection fraction patients.Methods:A retrospective cohort study consecutively enrolled 470 patients with heart failure with preserved ejection fraction from September 2014 to August 2017.According to the level of hs-cTnI,the patients were divided into the elevated level group(hs-cTnI>0.034 ng/mL in male and hs-cTnI>0.016 ng/mL in female)and the normal level group.All of the patients were followed up once every 6 months.Adverse cardiovascular events were cardiogenic death and heart failure hospitalization.Results:The mean follow-up period was 36.2±7.9 months.Cardiogenic mortality(18.6%[26/140]vs.1.5%[5/330],P<0.001)and heart failure(HF)hospitalization rate(74.3%[104/140]vs.43.6%[144/330],P<0.001)were significantly higher in the elevated level group.The Cox regression analysis showed that the elevated level of hs-cTnI was a predictor of cardiogenic death(hazard ratio[HR]:5.578,95%confidence interval[CI]:2.995-10.386,P<0.001)and HF hospitalization(HR:3.254,95%CI:2.698-3.923,P<0.001).The receiver operating characteristic curve demonstrated that a sensitivity of 72.6%and specificity of 88.8%for correct prediction of adverse cardiovascular events when a level of hs-cTnI of 0.1305 ng/mL in male and a sensitivity of 70.6%and specificity of 90.2%when a level of hs-cTnI of 0.0755 ng/mL in female were used as the cut-off value.Conclusion:Significant elevation of hs-cTnI(≥0.1305 ng/mL in male and≥0.0755 ng/mL in female)is an effective indicator of the increased risk of cardiogenic death and HF hospitalization in heart failure with preserved ejection fraction patients.