The Definition of Sarcomeric and Non-Sarcomeric Gene Mutations in Hypertrophic Cardiomyopathy Patients: A Multicenter Diagnostic Study Across Türkiye.

BACKGROUND: Hypertrophic cardiomyopathy is a common genetic heart disease and up to 40%-60% of patients have mutations in cardiac sarcomere protein genes. This genetic diagnosis study aimed to detect pathogenic or likely pathogenic sarcomeric and non-sarcomeric gene mutations and to confirm a final molecular diagnosis in patients diagnosed with hypertrophic cardiomyopathy. METHODS: A total of 392 patients with hypertrophic cardiomyopathy were included in this nationwide multicenter study conducted at 23 centers across Türkiye. All samples were analyzed with a 17-gene hypertrophic cardiomyopathy panel using next-generation sequencing technology. The gene panel includes ACTC1, DES, FLNC, GLA, LAMP2, MYBPC3, MYH7, MYL2, MYL3, PLN, PRKAG2, PTPN11, TNNC1, TNNI3, TNNT2, TPM1, and TTR genes. RESULTS: The next-generation sequencing panel identified positive genetic variants (variants of unknown significance, likely pathogenic or pathogenic) in 12 genes for 121 of 392 samples, including sarcomeric gene mutations in 30.4% (119/392) of samples tested, galactosidase alpha variants in 0.5% (2/392) of samples and TTR variant in 0.025% (1/392). The likely pathogenic or pathogenic variants identified in 69 (57.0%) of 121 positive samples yielded a confirmed molecular diagnosis. The diagnostic yield was 17.1% (15.8% for hypertrophic cardiomyopathy variants) for hypertrophic cardiomyopathy and hypertrophic cardiomyopathy phenocopies and 0.5% for Fabry disease. CONCLUSIONS: Our study showed that the distribution of genetic mutations, the prevalence of Fabry disease, and TTR amyloidosis in the Turkish population diagnosed with hypertrophic cardiomyopathy were similar to the other populations, but the percentage of sarcomeric gene mutations was slightly lower.

Gender-Related Differences in Patients with Acute Heart Failure: Observation from the Journey Heart Failure-Turkish Population Study.

BACKGROUND: Gender-related clinical variations in patients with acute heart failure have been described in previous studies. However, there is still a lack of research on gender differences in patients hospitalized for acute heart failure in Türkiye. The aim of this study is to compare the clinical features, in-hospital approaches, and outcomes of male and female patients hospitalized for acute heart failure. METHODS: Differences in clinical characteristics, medication prescription, hospital management, and outcomes between males and females with acute heart failure were investigated from the Journey Heart Failure-Turkish Population study. RESULTS: Nine hundred eighteen patients (57.2%) were men and 688 (42.8%) were women. Women were older than men (70.48 ± 13.20 years vs. 65.87 ± 12.82 years; P <.001). The frequency of comorbidities such as hypertension (72.7% vs. 62.4%, P <.001), diabetes (46.5% vs. 38.5%, P = .001), atrial fibrillation (46.5% vs. 33.4%, P <.001), New York Heart Association class III-IV symptoms (80.6% vs. 71.2%, P =.001), and dyspnea in the rest (73.8% vs. 68.3%, P =.044) were more common in women on admission. Male patients were more frequently hospitalized with reduced left ventricular ejection fraction (51.0% vs. 72.4%, P <.001). In-hospital mortality was higher among female patients (9.3% vs. 6.4%, P =.022). Higher New York Heart Association class, lower estimated glomerular filtration rate, higher N-terminal pro-B type natriuretic peptide on admission, and mechanical ventilation usage were the independent parameters of in-hospital mortality, whereas the female gender was not. CONCLUSION: Our study clearly demonstrated the diversity in presentation, management, and in-hospital outcomes of acute heart failure between male and female patients. Although left ventricular systolic functions were better in female patients, in-hospital mortality was higher. Recognizing these differences in the management of heart failure in different sexes will serve better results in clinical practice.

Effect of altitude on ticagrelor-induced dyspnea in patients with acute coronary syndrome.

OBJECTIVE: This study aimed to define the association between altitude and ticagrelor-associated dyspnea in patients with acute coronary syndrome (ACS). METHODS: We studied consecutive patients with de novo ACS who were admitted to two centers at a low altitude (18 and 25 m, n = 65) and two centers at a high altitude (1313 and 1041 m, n = 136). We managed them with ticagrelor between May 2017 and September 2017. Patients with ACS underwent an interventional procedure within <90 minutes in those with ST elevation and within <3 hours in those without ST elevation. We recorded the incidence of dyspnea in patients with ACS receiving ticagrelor therapy. RESULTS: The mean age was 59.5 ± 10 years, and the mean ejection fraction was 43% ± 18%. A total of 110 (56.7%) patients had ST elevation and 84 (43.3%) did not. There were no significant differences in cardiac risk factors, concurrent medications, or procedural variables between the two groups. Dyspnea developed during hospitalization in 53 (38%) patients from high-altitude centers and in 13 (20%) patients from low-altitude centers (66 patients represented 32% of the total ACS cohort). CONCLUSIONS: Dyspnea is a common multifactorial symptom in patients following development of ACS. Ticagrelor-induced dyspnea appears to be associated with altitude.

Hyperkalemia in chronic heart failure with renal dysfunction or diabetes mellitus: Results from the TREAT HF study.

OBJECTIVE: Chronic kidney disease (CKD) and diabetes mellitus (DM) are common comorbidities in heart failure (HF). Patients with HF are at a high risk of hyperkalemia, and are therefore undertreated with respect to disease-modifying therapies. The Turkish Research Team-Heart Failure (TREAT HF) data were analyzed for the evaluation of hyperkalemia in real-life clinical practice in HF patients with CKD or DM. METHODS: The TREAT HF is a multicenter, national, observational registry. In this study, potassium levels of 1028 patients with HF were analyzed. Hyperkalemia is defined as blood potassium levels >5 mEq/L and evaluated based on the CKD, DM, HF medications, and New York Heart Association (NYHA) classes. RESULTS: Overall, 14.3% of patients (n=147) were found to have hyperkalemia. Hyperkalemia was more prevalent in patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 than those with eGFR ≥60 mL/min/1.73 m2 (17.7% and 12%, respectively, p=0.010). Hyperkalemia was present in 10.9% (n=23) of patients with stage 1, 12.6% (n=50) with stage 2, 17.0% (n=52) with stage 3, and 19.5% (n=22) with stage 4-5 CKD. Hyperkalemia was higher in patients with DM (20.5% vs 12.3%, p=0.001). Furthermore, hyperkalemia was much higher in patients with DM with eGFR <60 mL/min/1.73 m2 (25.2%). The rate of hyperkalemia increased across NYHA categories (NYHA-I: 9.8%, NYHA-II: 12.8%, NYHA-III: 14.4%, and NYHA-IV: 23.4%, p=0.030). In patients with stage 4-5 CKD who were receiving renin-angiotensin-aldosterone system (RAAS) inhibitor therapy, more patients had hyperkalemia than those not receiving RAAS inhibitor therapy (23.4% and 12.5%, respectively). CONCLUSION: In clinical practice, 14.3% of all patients with HF, 17.7% of all patients with CKD, and 20.5% of all patients with DM have hyperkalemia. The risk of hyperkalemia increases with advanced stages of CKD or NYHA and the risk is higher in patients receiving RAAS inhibitor therapy.

Marital status and outcomes in chronic heart failure: Does it make a difference of being married, widow or widower?

OBJECTIVE: We aimed to compare the outcomes of chronic heart failure (HF) patients with reduced ejection fraction (CHFrEF) in the Turkish Research Team in HF (TREAT-HF) registry according to marital status with a specific focus on being the widowed (widow/widower) versus the married. METHODS: TREAT-HF is a network, enrolling CHFrEF with a follow up for HF-related hospitalization (HFrH) and all-cause mortality (ACM). In this cohort, the widowed patients were compared with patients who were married before and after propensity score (PS) matching analysis. RESULTS: There were 723 cHFrEF patients with a complete dataset, including reported marital status at baseline for this analysis. Out of 723 patients with HF, 37 "never-married" and "divorced" patients were excluded from the analysis. Then, out of 686 remaining patients with HF, who had at least one reported marriage in the database, widowed patients with HF (n=124) were compared with married patients (n=562). The mean follow up period was 21±12 months up to 48 months. The widowed patients had a higher risk of HFrH (p=0.047), although ACM remained similar compared to married patients (p=0.054). After PS matching, HFrH remained more frequent among the widowed compared with the married (p=0.039) although ACM yielded similar rates. Of note, it was shown that being a widower (p=0.419) was not linked to increased risk of HFrH during follow up contrary to being a widow (p=0.037) despite similar age, ejection fraction, creatinine, NYHA functional class distribution and a similar rate of life-saving medications. CONCLUSION: PS matching analysis yielded that the widowed had increased the risk for HFrH. Of note, widowers did not seem to have an increased risk for HFrH, contrary to widows.

Cancer antigen-125 is a predictor of mortality in patients with pulmonary arterial hypertension.

BACKGROUND: Carbohydrate antigen 125 (CA 125), known as a tumor marker for ovarian cancer, has been reported to increase and be associated with severity in heart failure and chronic obstructive pulmonary disease. Patients with pulmonary arterial hypertension may also die due to developing right heart failure. The aim of this study is to evaluate the prognostic role of CA-125 in PAH patients. METHODS: A total of 40 consecutive patients with PAH were evaluated prospectively. The mean age of patients was 52 ± 11 years (12% males, 88% females) with a median follow-up period of 16 months. RESULTS: After follow-up period, 12 out of 40 patients (30%) died. CA-125 levels were higher among those who died compared to those who survived [78.5 (11.0-292) vs. 27.5 (2.10-138) U/ml, p = 0.001]. The optimal cut-off value of CA-125 to predict mortality was found as 35.29 U/ml, with 85.7% specificity and 75% sensitivity. In multivariable Cox proportional-hazards model with forward stepwise method; CA-125 > 35.32 U/ml on admission (HR = 7.645, 95% CI: 1.356-43.121, p = 0.021), age (HR = 1.132, 95% CI: 1.040-1.233, p = 0.004), TAPSE (HR = 0.740, 95% CI: 0.549-0.998, p = 0.048) and uric acid (HR = 1.444, 95% CI: 1.022-2.042, p = 0.037) remained associated with an increased risk of death. CONCLUSION: In this study, we showed for the first time that serum CA-125 values were an independent predictor for the long-term mortality in PAH patients.

Increased frequency of occurrence of bendopnea is associated with poor outcomes in heart failure outpatients.

BACKGROUND: Relationship between the frequency of occurrence of bendopnea during the daily life of heart failure (HF) outpatients and clinical outcomes has never been evaluated before. METHODS: Turkish Research Team-Heart Failure (TREAT-HF) is a network between HF centres, which undertakes multicentric observational studies in HF. Herein, the data including stable 573 HF patients with reduced ejection fraction out of seven HF centres were presented. A questionnaire was filled by the patients, with the question 'Do you experience shortness of breath while tying your shoelace?', assessing the presence and frequency of bendopnea. RESULTS: To the question related to bendopnea, 48% of the patients answered 'yes, every time', 31% answered 'yes, sometimes', and 21% answered 'No'. Patients were followed for an average of 24 ± 14 months, and the patients who answered 'yes, every time' and 'yes, sometimes' to the bendopnea question were found having increased risk for both HF-related hospitalisations (HR:3.2, p < .001- HR:2.8, p = .005) and composite outcome consisting of 'HF-related hospitalisations and all-cause death in the multi-variate analysis (HR:3.1, p < .001- HR:3.0, p < .001). Kaplan Meier analysis for HF-related hospitalisation, all-cause death, and the composite of these were provided for these three groups, yielding significant and graded divergence curves with the best prognosis in 'no' group, with the moderate prognosis in 'sometimes' group, and with the worst prognosis in the 'every time' group. CONCLUSION: For the first time in the literature, our study shows that the increased frequency of bendopnea occurrence in daily life is associated with poor outcomes in HF outpatients.

Hyponatremia is associated with occurrence of atrial fibrillation in outpatients with heart failure and reduced ejection fraction.

OBJECTIVES: Hyponatremia and atrial fibrillation (AF) have been established as strong predictors for worse clinical outcomes in patients with heart failure (HF). However, little is known about hyponatremia in relation to the occurrence of AF. This study aims to investigate the possible relationship between hyponatremia and AF in patients with chronic HF and reduced ejection fraction (HFrEF). METHODS: Turkish research team-HF (TREAT-HF) is a network that has been undertaking multicenter, observational cohort studies on HF. A total of 880 patients who had plasma sodium measurement in TREAT-HF data set were included in this study. Hyponatremia was defined as a plasma sodium level of ≤135 mmol/L. The patients were classified into hyponatremia (n=213) or normonatremia (n=667) based on the sodium level. RESULTS: The rate of AF was found to be 33.3% in patients with hyponatremia and 18.8% in patients with normonatremia (p<0.001). Univariate analysis demonstrated an association between hyponatremia and AF. Furthermore, in multivariate logistic regression model, hyponatremia was also found to be significantly and independently associated with the occurrence of AF (odds ratio [OR]=2.457, 95% confidence interval [CI]=1.586-3.806, p<0.001) in addition to other well-known risk factors for AF. CONCLUSION: The results of this study showed that AF was more prevalent in outpatients with HFrEF and hyponatremia than in those with HFrEF and normonatremia. These results also suggest that hyponatremia is independently associated with the occurrence of AF.

Evaluation of Atrial Electromechanical Delay to Predict Atrial Fibrillation in Hemodialysis Patients.

Background and objective: Prevalence of atrial fibrillation is higher in hemodialysis patients as compared to the general population. Atrial electromechanical delay is known as a significant predictor of atrial fibrillation. In this study, we aimed to reveal the relationship between atrial electromechanical delay and attacks of atrial fibrillation. Materials and methods: The study included 77 hemodialysis patients over 18 years of age giving written consent to participate in the study. The patients were divided into two groups based on the results of 24-h Holter Electrocardiogram (Holter ECG) as the ones having attacks of atrial fibrillation and the others without any attack of atrial fibrillation. Standard echocardiographic measurements were taken from all patients. Additionally, atrial conduction times were measured by tissue Doppler technique and atrial electromechanical delays were calculated. Results: Intra- and interatrial electromechanical delay were found as significantly lengthened in the group of patients with attacks of atrial fibrillation (p = 0.03 and p < 0.001 respectively). The optimal cut-off time for interatrial electromechanical delay to predict atrial fibrillation was >21 ms with a specificity of 79.3% and a sensitivity of 73.7% (area under the curve 0.820; 95% confidence interval (CI), 0.716⁻0.898). In the multivariate logistic regression model, interatrial electromechanical delay (odds ratio = 1.230; 95% CI, 1.104⁻1.370; p < 0.001) and hypertension (odds ratio = 4.525; 95% CI, 1.042⁻19.651; p = 0.044) were also associated with atrial fibrillation after adjustment for variables found to be statistically significant in univariate analysis and correlated with interatrial electromechanical delay. Conclusions: Interatrial electromechanical delay is independently related with the attacks of atrial fibrillation detected on Holter ECG records in hemodialysis patients.

Demonstration of Ischemia in Myocardial Perfusion Scintigraphy before Coronary Revascularization Decreases Acute Coronary Syndrome-related Hospitalizations.

In this study, we compared the patients who underwent coronary angiography (CAG), followed by revascularization by coronary artery stent implantation according to the CAG results without any evidence of ischemia with myocardial perfusion scintigraphy (MPS), and the patients who underwent revascularization by coronary artery stent implantation following the detection of ischemia in MPS before CAG in terms of the mortality and hospitalization due to acute coronary syndrome (ACS). Between January 2009 and January 2016, a total of 407 patients (52% males, 48% females; mean age: 66 ± 9 years; range: 40-85 years) who underwent CAG following diagnosis of stable angina and underwent coronary artery stenting were retrospectively analyzed. The patients were divided into two groups: Group 1 (n = 200) included those who had MPS before CAG and in whom ischemia was detected and stent was implanted, and Group 2 (n = 207) included those who had stent implantation according to the CAG results without prior MPS. The mean follow-up was 40 ± 18 months. Although there was no significant difference in the mortality rates between the groups, the rate of hospitalization due to ACS was significantly lower in Group 1 (P = 0.112 vs. P = 0.022, respectively). According to the multivariate Cox-regression analysis, demonstration of ischemia in MPS before revascularization, statin use, clopidogrel use, and higher high-density lipoprotein cholesterol levels were found to be associated with a reduced risk of ACS-related hospitalization, whereas the presence of diabetes mellitus and smoking was found to be associated with an increased risk of ACS-related hospitalization.

Mean Platelet Volume as a Predictor of Heart Failure-Related Hospitalizations in Stable Heart Failure Outpatients with Sinus Rhythm.

BACKGROUND: In this study, we investigated the relationship between the mean platelet volume (MPV) with mortality and heart failure (HF)-related hospitalization in stable chronic HF outpatients with reduced ejection fraction (HFrEF) and with sinus rhythm (SR). METHODS: This retrospective cohort study included 197 consecutive stable chronic HFrEF outpatients with SR, who were admitted to our cardiology outpatient clinics for examination between January 2014 and January 2015. According to the receiver-operating characteristic curve analysis, the optimal cut-off value of MPV to predict HF-related hospitalization was > 9.1 fL. Patients were classified into two categories according to threshold MPV levels, as group I with MPV ≤ 9.1 fL and group II with MPV > 9.1 fL. RESULTS: The mean age of patients was 65 ± 13 years. The mean follow-up duration was 10 ± 3 months, and 44 patients (22%) succumbed to cardiovascular (CV) death. The rate of CV mortality was similar between the two groups (21% vs. 24%, p = 0.649). However, the rate of patients who experienced HF-related hospitalization was lower in group I compared with group II (41% vs. 87%, p < 0.001, respectively). Univariate analysis demonstrated associations of many clinical factors in addition to increased MPV > 9.1 fL with HF-related hospitalization; however, In the multivariate Cox proportional-hazards model, only increased MPV > 9.1 fL (HR: 2.895, 95% CI: 1.774-4.724, p < 0.001), systolic pulmonary artery pressure level (HR: 1.018, 95% CI: 1.001-1.036, p = 0.048) and pre-admission beta blocker use (HR: 0.517, 95% CI: 0.305-0.877, p = 0.014) remained associated with a risk of HF-related hospitalization. CONCLUSIONS: The mean platelet volume might be a useful parameter for risk stratification with regard to HF-related hospitalization in HFrEF outpatients with SR.

Cancer Antigen 125 is Associated with Length of Stay in Patients with Acute Heart Failure.

Length of stay is the primary driver of heart-failure hospitalization costs. Because cancer antigen 125 has been associated with poor morbidity and mortality rates in heart failure, we investigated the relationship between admission cancer antigen 125 levels and lengths of stay in heart-failure patients. A total of 267 consecutive patients (184 men, 83 women) with acute decompensated heart failure were evaluated prospectively. The median length of stay was 4 days, and the patients were classified into 2 groups: those with lengths of stay ≤4 days and those with lengths of stay >4 days. Patients with longer lengths of stay had a significantly higher cancer antigen 125 level of 114 U/mL (range, 9-298 U/mL) than did those with a shorter length of stay (19 U/mL; range; 3-68) (P <0.001). The optimal cutoff level of cancer antigen 125 in the prediction of length of stay was >48 U/mL, with a specificity of 95.8% and a sensitivity of 96% (area under the curve, 0.979; 95% confidence interval [CI], 0.953-0.992). In the multivariate logistic regression model, cancer antigen 125 >48 U/mL on admission (odds ratio=4.562; 95% CI, 1.826-11.398; P=0.001), sodium level (P<0.001), creatinine level (P=0.009), and atrial fibrillation (P=0.015) were also associated with a longer length of stay after adjustment for variables found to be statistically significant in univariate analysis and correlated with cancer antigen 125 level. In addition, it appears that in a cohort of patients with acute decompensated heart failure, cancer antigen 125 is independently associated with prolonged length of stay.

Right Ventricular Dysfunction Complicates Time in Therapeutic Range in Heart Failure Patients Receiving Warfarin.

AIM: We aimed to evaluate the effect of echocardiographically demonstrated right ventricular dysfunction (RVD) on time in therapeutic range (TTR) in heart failure (HF) patients receiving warfarin therapy. METHODS: A total of 893 consecutive HF patients were included and classified into 4 different subgroups: HF with preserved ejection fraction (HFpEF) without RVD (n = 373), HF with reduced EF (HFrEF) without RVD (n = 215), HFpEF with RVD (n = 106) and HFrEF with RVD (n = 199). Groups were compared according to baseline, demographic and clinical data and the characteristics of warfarin therapy. RESULTS: Presence of RVD yielded lower median TTR values both in HFpEF and HFrEF patients. RVD, current smoking, New York Heart Association functional class III/IV, hypertension, diabetes mellitus, pulmonary disease, prior transient ischemic attack or stroke, chronic kidney disease (CKD) stage 4/5 and CKD stage 3 were found to be independent predictors of poor anticoagulation control in multivariate logistic regression analysis. CONCLUSIONS: The present study demonstrated that presence of RVD in HF increases the risk for poor anticoagulation.

Prediction of fractional flow reserve with angiographic DILEMMA score.

OBJECTIVE: Angiographic assessment of stenosis has limited predictive value for functionally significant lesions compared with fractional flow reserve (FFR). The recently developed angiographic DILEMMA score, which consists of minimal lumen diameter (MLD), lesion length (LL) and Bypass Angioplasty Revascularization Investigation (BARI) Myocardial Jeopardy Index (MJI) was found to have diagnostic value in predicting FFR ≤0.80. The present study was an investigation of prediction of FFR ≤0.80 using DILEMMA score and its relationship to resting distal coronary artery pressure/aortic pressure (Pd/Pa). METHODS: Records of consecutive patients who underwent coronary angiography and FFR were retrospectively analyzed. Assessment of MLD and LL was performed using quantitative coronary angiography. BARI MJI was calculated using angiographic calculation index. RESULTS: A total of 185 pressure wire analysis data sets from 150 patients were analyzed retrospectively. There were 82 lesions in FFR >0.80 group and 103 lesions in FFR ≤0.80 group. Negative correlation was found between FFR and DILEMMA score (r=-0.494; p<0.001), FFR and BARI-MJI (r=-0.378; p<0.001), and between FFR and LL (r=-0.314; p<0.001). Positive correlation was found between FFR and baseline Pd/Pa (r=0.713; p<0.001), and between FFR and MLD (r=0.415; p<0.001). DILEMMA score had negative correlation with resting Pd/Pa (r=-0.389; p<0.001). In receiver operating characteristic analysis for diagnosing FFR≤0.80, area under curve values of resting Pd/Pa, DILEMMA score, MLD, BARI-MJI, and LL were 0.862, 0.793, 0.780, 0.728, and 0.686, respectively. CONCLUSION: DILEMMA score had moderately strong correlation with FFR and good accuracy in diagnosing significant FFR, but it had weak correlation with resting Pd/Pa.

Plasma osmolality predicts mortality in patients with heart failure with reduced ejection fraction.

BACKGROUND: Heart failure (HF) is a fatal disease. Plasma osmolality with individual impacts of sodium, blood urea nitrogen (BUN), and glucose has not been studied prognostically in patients with HF. AIM: This study aims to investigate the impact of serum osmolality on clinical endpoints in HF patients. METHODS: A total of 509 patients (383 males, 126 females) with HF with reduced ejection fraction in three HF centres were retrospectively analysed between January 2007 and December 2013. Follow-up data were completed for 496 patients. Plasma osmolality was calculated as (2 × Na) + (BUN/2.8) + (Glucose/18). Quartiles of plasma osmolality were produced, and the possible relationship between plasma osmolality and cardiovascular mortality was investigated. RESULTS: The mean follow-up was 25 ± 22 months. The mean age was 56.5 ± 17.3 years with a mean EF of 26 ± 8%. The mean levels of plasma osmolality were as follows in the quartiles: 1st % = 280 ± 6, 2nd % = 288 ± 1, 3rd % = 293 ± 2 (95% confidence interval [CI] 292.72-293.3), and 4th % = 301 ± 5 mOsm/kg. The EF and B-type natriuretic peptide levels were similar in the four quartiles. Univariate and multivariate analyses in the Cox proportional hazard model revealed a significantly higher rate of mortality in the patients with hypo-osmolality. The Kaplan-Meier plot showed graded mortality curves with the 1st quartile having the worst prognosis, followed by the 4th quartile and the 2nd quartile, while the 3rd quartile was shown to have the best prognosis. CONCLUSIONS: Our study results suggest that normal plasma osmolality is between 275 and 295 mOsm/kg. However, being close to the upper limit of normal range (292-293 mOsm/kg) seems to be the optimal plasma osmolality level in terms of cardiovascular prognosis in patients with HF.