Prognosis In Heart Failure Patients Research Articles

The role of NT-proBNP as a predicting factor for mortality in patient admitted with acute heart failure

Currently cardiac biomarkers such as B-type natriuretic peptide (BNP) and N-terminal peptide (NT-proBNP) were widely used to diagnose HF in dyspnoea patients. NT-proBNP is not only also useful for the diagnosis of uncertain dyspnoea patients, but it also plays a crucial role to determine the short-term prognosis of heart failure patients This present study is to assess the role of NT-proBNP as a predicting factor for mortality inpatient admitted with Acute Heart Failure.

Development and Validation of a Prognostic Model Based on Clinical Biomarkers for Heart Failure in Adult Patients Following Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: Heart failure (HF) is an uncommon but one of the most serious types of cardiovascular complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the prognostic factors of HF after allo-HSCT remain unknown, and there is currently no prognostic model for HF after allo-HSCT. In this study, we investigated the clinical features and prognosis of patients with HF after allo-HSCT. A prognostic model based on clinical biomarkers, which combined variables that are readily available in clinical practice, that is capable of predicting 2-month mortality of HF patients after allo-HSCT was developed and validated. Methods: In our retrospective study, 154 patients with HF after allo-HSCT from 2008 to 2021 were identified. One hundred patients were assigned to the derivation cohort and the remaining 54 patients were assigned to the external validation cohort according to the time of transplantation. We first calculated the univariable association of each variable with 2-month mortality in the derivation cohort. Second, the variables with p values less than 0.1 in the univariate analysis were further included as candidate predictors in the multivariate analysis using a backward stepwise logistic regression model. The variables that remained in the final model based on the outcomes of the multivariate analysis in the derivation cohort were identified as independent prognostic factors. A scoring system to predict the prognosis of HF after allo-HSCT was also established, and scores were assigned to the prognostic factors based on the regression coefficient. Results: Using multivariable logistic regression methods with stepwise variable selection, four highly significant independent prognostic factors for the two-month mortality of HF were identified: pulmonary infection (p=0.005; odds ratio [OR], 6.89; 95% confidence interval [CI], 1.93-29.13), Grades III to IV acute graft-versus-host disease (severe aGVHD) (p=0.033; odds ratio [OR], 3.62; 95% confidence interval [CI], 1.15-12.69), lactate dehydrogenase (LDH)>426 U/L (p=0.049; odds ratio [OR], 3.02; 95% confidence interval [CI], 1.00-9.32) and brain natriuretic peptide (BNP)>1799 pg/ml (p=0.026; odds ratio [OR], 3.44; 95% confidence interval [CI], 1.16-10.56). We also included cardiac troponin I (cTNI) (p=0.069; odds ratio [OR], 2.93, 95% confidence interval [CI], 0.94-29.13) in our final 5-predictor prognostic model. A risk grading model termed the BLIPS score (BNP, LDH, cardiac troponin I, pulmonary infection, severe aGVHD) was constructed according to the regression coefficients. BNP level>1799 pg/mL, LDH level>426 U/L, cTNI level>100 pg/ml, and severe aGVHD were each assigned one point, and pulmonary infection was assigned two points. The points scored for each of these five factors were added to yield the overall risk score, which ranged from zero to six. Patients were stratified into a low-risk group (0-2 points), an intermediate-risk group (3-4 points) and a high-risk group (5-6 points). The validated internal c-statistic was 0.870 (95% CI, 0.798-0.942), and the external c-statistic was 0.882 (95% CI, 0.791-0.973). According to the calibration plots, the model-predicted probabilities showed a good correlation with the actual observed frequencies. Decision curve analysis indicated that the clinical implementation of the prognostic model could benefit HF patients. The Kaplan‒Meier estimations of overall survival revealed good separation between these risk groups. We generated a risk heatmap for the BLIPS model to visualize the risk estimates derived from the individual prognostic factor profile. Conclusions: Patients who develop HF after allo-HSCT have a poor prognosis. An integrated prognostic model based on clinical biomarkers (BLIPS) was developed and externally validated, and this is the first straightforward scoring model that incorporates clinical and laboratory risk factors to evaluate the 2-month mortality of patients with HF after receiving allo-HSCT to treat hematological malignancies. This model can be effectively utilized to help improve the survival and prognosis of HF patients by accelerating the early identification of patients at a high risk of mortality and contributing to the appropriate implementation of urgent medical support. Disclosures: No relevant conflicts of interest to declare.

Abstract 9373: Single Evaluation of Body Mass-Corrected Estimated Plasma Volume at Discharge Predicts Prognosis of Heart Failure Patients

Background: Estimated plasma volume(ePV) is a parameter of body fluid volume trends in the same patient and also an indicator for residual congestion. Patients with heart failure often have difficulty achieving adequate body fluid volume. We investigated the post-discharge prognosis of heart failure patients with a one-time evaluation of ePV at discharge corrected for body mass index (BMI). Methods: This is a single-center, prospective observational study. A total of consecutive 1268 heart failure hospitalizations, excluding acute coronary syndromes, from January 2018 to December 2021 were included. We evaluated 767 patients, excluding repeat hospitalizations of the same patient (366 cases), in-hospital deaths (54 cases), transfers for cardiac surgery and forced discharges (39 cases), and missing data (42 cases). A prognosis investigation was conducted for patients who haven’t visited our hospital for more than one year. BMI and ePV (ml, Hakim's formula) were calculated from height, weight, and hematocrit at discharge. Survival analysis was performed with ePV divided by BMI (ePV/BMI). Primary endpoint was composite of all-cause mortality and heart failure re-hospitalization. Results: median of 372 days of post-discharge observation, 205 deaths, and 336 composite endpoints were observed. ePV/BMI was categorized into three quartiles [low group (65.34-96.8), middle group (96.9-111.9) and high group (112.0-175.8)]. Survival analysis by ePV/BMI three tertiles showed a combined endpoint of death + rehospitalization (48.8 vs 69.2 vs 74.9%, log-rank P<0.001) and death (11.7 vs 20.9 vs 24.7%, log-rank P<0.001) at three years, respectively. Multivariable Cox proportional hazard model with covariant univariable predictive factors (age, severe kidney dysfunction, beta-blocker, angiotensin-converting enzyme inhibitor, psychotropic or cognitive medicines, in-hospital blood transfusion, low nutritional status) shows higher ePV/BMI tertile (HR1.44, 95%CI:1.26-1.64, p<0.001), as well as the continuous variable of ePV/BMI (HR1.02, 95%CI:1.01-1.03, p<0.001), is a predictive factor of the composite endpoint. Conclusion: Even after therapeutic intervention, ePV/BMI at discharge is a useful predictor of heart failure outcome.

High serum fibroblast growth factor 21 levels were related to the prognosis and ventricular remodeling of heart failure patients with mildly reduced and reduced ejection fraction.

Previous studies have shown that fibroblast growth factor 21 (FGF21) is involved in the ventricular remodeling process in heart failure with preserved ejection fraction (HFpEF). We hypothesized that high levels of FGF21 correlated with the ventricular remodeling of heart failure patients with mildly reduced (HFmrEF) and reduced ejection fraction (HFrEF). A total of 203 participants with HFmrEF or HFrEF were enrolled and followed up from June 2018 to June 2021. 68 subjects without heart failure (HF) underwent physical examinations during the same time were selected as the control group. The primary endpoint was the occurrence of major adverse cardiovascular events (MACEs), which were defined as all-cause or cardiac mortality and rehospitalization for decompensation. Serum FGF21 levels were measured early the next morning after admission using enzyme-linked immunosorbent assay (ELISA). The FGF21 levels were significantly higher in patients with HFmrEF or HFrEF than that in the control group (213.57 ± 42.65pg/mL, 222.93 ± 34.36pg/mL vs 171.00 ± 12.86pg/mL, p < .001). The serum levels of FGF21 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were both higher in the endpoint event group than those of non-endpoint event group regardless of the HFmrEF or HFrEF group (p < .001). Spearman's correlation revealed that FGF21 was positively correlated with left ventricular end-systolic diameter left ventricular end-diastolic diameter left ventricular mass index (p < .01). Moreover, there was a negative correlation between FGF21 and left ventricular ejection fraction in addition to relative wall thickness (p < .001). The area under the receiver operating characteristic (ROC) curve (AUC) of FGF21 was 0.874. The optimal cut-off value of FGF21 determined by ROC curve was 210.11pg/mL. The Kaplan-Meier analysis demonstrated that the low FGF21 levels group had an increased MACE-free survival rate compared with the high FGF21 levels group. On univariate and multivariate Cox analysis, it was seen that both serum FGF21 and NT-proBNP were independent predictors of a poor prognosis in HF patients. Baseline levels of FGF21 and NT-proBNP were related to the ventricular remodeling of patients with a mildly reduced or reduced ejection fraction. FGF21 and NT-proBNP both had good prognostic value for MACEs in heart failure patients with a mildly reduced and reduced ejection fraction.

Combined effects of physical activity and sedentary behavior on all-cause mortality in heart failure patients: A cohort study of national health and nutrition examination survey analysis.

BackgroundPhysical activity and sedentary behavior are independently related to the risk of cardiovascular disease. Physical activity is recognized as having a protective effect, while being sedentary seems to be adverse. Nonetheless, the interactions between physical activity and sedentary behavior and the combined effect on the prognosis of heart failure patients remain unclear.Methods and resultsThis cohort study included 886 heart failure patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Physical activity and sedentary behavior were assessed by the NHANES questionnaires. The all-caused deaths of enrolled subjects were identified from National Death Index (NDI) database. During a median follow-up of 51 months, 321 (36.2%) deaths from any causes occurred. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence interval (CI) for the all-cause mortality in heart failure patients associated with physical activity and sedentary behavior. Physical activity was independently associated with lower mortality [HR = 0.51, 95% CI (0.38-0.68), p < 0.001] and sedentary behavior was associated with adverse prognosis [HR = 1.79, 95% CI (1.41–2.28), p < 0.001]. Kaplan–Meier survival curve showed that physical activity appeared to attenuate the negative consequences of SB, while sedentary behavior increased the all-cause mortality, particularly those without physical activity.ConclusionPhysical activity has a protective effect on HF patients’ prognosis, particularly those with sedentary behavior. Sedentary behavior independently exhibited a negative association in populations without physical activity, while it does not increase mortality in those with moderate physical activity.

The Ratio of Urine N-Terminal Pro B-Type Natriuretic Peptide to Cyclic Guanosine Monophosphate Predicts Emergency Department Visits for Heart Failure

Introduction: Emergency department (ED) visits for decompensated heart failure (HF) are frequent and associated with poor long-term outcomes. Plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) and cyclic guanosine monophosphate (cGMP) are used in diagnosis and prognosis of HF patients, while clinical values of urine NT-proBNP/cGMP ratio have been rarely explored. This study aims to compare the predictive values of urine NT-proBNP/cGMP ratio versus plasma NT-proBNP for ED visits for decompensated HF. Methods: This prospective study included 126 HF patients with reduced left ventricular ejection fraction (<50%) and without chronic kidney disease. Baseline data included demographics, co-morbidities, and co-medications. Medical records were used to determine the incidence of ED visits for decompensated HF during the 3 months following the last visit. Results: Patients with subsequent ED visits had significantly higher levels of plasma and urine NT-proBNP and urine cGMP in than those without. Multivariate Cox regression analysis disclosed that Lg₁₀urine NT-proBNP/cGMP was an independent risk factor for subsequent ED visits (OR = 3.267; 95% CI: 1.105–9.663; p = 0.032). ROC analysis revealed an Lg₁₀urine NT-proBNP/cGMP ratio optimal cut-off value of 0.1706 (AUC, 0.700; 95% CI: 0.543–0.857; p = 0.036) for predicting subsequent HF-related ED visits. Conclusion: A single measurement of urinary NT-proBNP/cGMP ratio is predictive of subsequent ED visits for decompensated HF. This noninvasive and easy measurement may be a clinically useful tool for identifying a subset of patients at higher risk of ED visits.

Sacubitril/valsartan treatment: effect on left ventricular remodelling and fibrosis assessed by novel heart failure biomarkers

Abstract Background In patients with heart failure and reduced ejection fraction (HFrEF), treatment with sacubitril-valsartan (SAC/VAL) reduces N-terminal B-type natriuretic peptide (NT-proBNP) levels and appears to have a beneficial effect on ventricular remodelling (VR), although the mechanism of this effect has yet to be established. ST2 is a novel biomarker reflecting inflammation and haemodynamic stress, closely related to the pathophysiology of heart failure (HF), fibrosis and VR. Several studies have shown that elevated levels of ST2 are associated with increased risk of developing HF and worse prognosis, being an independent predictor of adverse clinical outcomes, and even establishing a correlation with clinical changes and NT-proBNP levels. Purpose To evaluate the effect of SAC/VAL treatment on left ventricular remodelling and fibrosis in patients with HFrEF by monitoring ST2 and NTproBNP levels during follow-up. Methods Prospective single-centre, open-label, single-group, prospective study including patients with HFrEF and NYHA functional class II–IV, under follow-up in our HF Unit from April 2018 to July 2020 with a 12-month follow-up for each patient. Biomarker measurements and echocardiography were performed at baseline, 6 and 12 months after initiation of SAC/VAL treatment. In addition, cardiac magnetic resonance imaging (CMRI) was performed at baseline and after 12 months of treatment. Results 68 patients were included (mean age 65.63±11.78 years; 29.4% female). Baseline characteristics are shown in table 1. The mean baseline NT-proBNP and ST2s concentration was 2238.24±2148.65 pg/mL and 42.31±28.38 ng/mL respectively, with a statistically significant reduction after 12 months with SAC/VAL (NTproBNP 701.65±778.13 pg/mL and ST2 30.22±9.70 ng/mL; p&amp;lt;0.01 in both cases). In addition, there was an improvement in left ventricular ejection fraction (LVEF) on echocardiography from 31.01±5.65% at baseline to 45.03±9.45% at 12 months (p&amp;lt;0.01). We also observed a statistically significant reduction in left ventricular end-diastolic and end-systolic diameter at 12 months from baseline (60.86±4.99 mm and 57.35±5.36 mm, p&amp;lt;0.01; 40.70±3.76 mm and 37.23±4.37 mm, p&amp;lt;0.01). These data suggesting reverse remodelling were also confirmed with CMRI, finding improved LVEF (32.90±6.65% vs 46.22±11.1%, p&amp;lt;0.01) and reduced end-diastolic (192.06±60.63 and 160.73±49.68, p&amp;lt;0.01) and end-systolic (125.28±52.07 and 90.74±41.79, p&amp;lt;0.01) volumes. During follow-up there were no alterations in renal function (creatinine 0.98±0.28 mg/dL at baseline, 1.03±0.32 mg/dL at 12 months, p=0.04) or potassium levels (4.50±0.40 mEq/L at baseline, 4.76±0.38 mEq/L at 12 months, p=0.22). Conclusion SAC/VAL treatment is associated with a reduction in NT-proBNP and ST2 concentrations which seems to support its beneficial effect on ventricular remodelling, allowing its monitoring to assess the evolution and prognosis of HF patients. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Novartis

Factors associated with health-related quality of life in heart failure in 23,000 patients from 40 countries: results of the global congestive heart failure research program

Abstract Background Poor health-related quality of life (HRQL) is common in heart failure (HF) and strongly predicts death and HF hospitalization in all regions of the world. Understanding facors associated with HRQL could therefore lead to improved prognosis in HF patients. Despite that the majority of HF occurs in low- and middle-income countries, there are limited data characterizing self-perceived health HRQL and its correlates in these settings. Purpose To examine clinical and social correlates of HRQL in patients with HF from high- (HIC), upper middle- (UMIC), lower middle-(LMIC) and low-income (LIC) countries. Methods Between 2017 and 2020, we enrolled 23,292 patients with HF (32% inpatients, 61% men) from 40 countries in the Global Congestive Heart Failure Study. We recorded HRQL at baseline using Kansas City Cardiomyopathy Questionnaire (KCCQ)-12. In a cross-sectional analysis, we compared age- and sex-adjusted mean KCCQ-12 summary scores (SS: 0–100, higher=better) between patients from different country income levels. We used multivariable linear regression examining correlations (estimates expressed as β-coefficients) of KCCQ-12-SS with sociodemographic-, comorbidity-, treatment- and symptom-covariates. The adjusted model (37 covariates) was informed by univariable findings, clinical importance and backward selection. We used partial R2-estimates to understand the contribution to the variability in KCCQ-12-SS of 4 different groups of covariates. (sociodemographic, comorbidities, treatments and signs and symptoms of congestion). Results Mean age was 63 years and 40% were in NYHA class III–IV. Average HRQL was 55± SD 0.5. It was 62.5 (95% CI 62.0–63.1) in HIC, 56.8 (56.1–57.4) in UMIC, 48.6 (48.0–49.3) in LMIC, and 38.5 (37.3–39.7) in LICs (p&amp;lt;0.0001). Strong correlates (β-coefficient [95% CI]) of KCCQ-12-SS were NYHA class III vs class I/II (−12.1 [−12.8 to −11.4] and class IV vs. class I/II (−16.5 [−17.7 to −15.3]), effort dyspnea (−9.5 [−10.2 to −8.8]) and living in LIC vs. HIC (−5.8 [−7.1 to −4.4]). Symptoms explained most of the KCCQ-12-SS variability (partial R2=0.32 of total adjusted R2=0.51), followed by sociodemographic factors (R2=0.12). Results were consistent in populations across income levels. Conclusion The most important correlates of HRQL in HF patients relate to HF symptom severity, irrespective of country-income level. Improved symptom control may have a big impact on HRQL, especially in LICs. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Bayer AG

Trimethyllysine, a trimethylamine N-oxide precursor, predicts the presence, severity, and prognosis of heart failure

Background and aimsIntestinal flora metabolites are associated with cardiovascular (CV) diseases including heart failure (HF). The carnitine precursor trimethyllysine (TML), which participates in the generation of the atherogenic-related metabolite trimethylamine N-oxide (TMAO), was found to be related to poor prognosis in patients with CV diseases. The aim of the present study was to examine the relationship between TML and stable chronic HF.Methods and resultsIn total, 956 subjects including 471 stable chronic HF and 485 non-HF patients were enrolled in the present cohort study and subjects with stable HF were followed up for 2.0 ± 1.1 years. Serum levels of TML and TMAO were measured by liquid chromatography mass spectrometry in tandem. TML levels were significantly elevated in patients with HF compared with non-HF patients and were positively correlated with N-terminal pro-brain natriuretic peptide (NTproBNP) levels (r = 0.448, P < 0.001). TML was associated with the presence of HF after adjusting for age, sex, complications, traditional clinical factors, and TMAO (tertile 3 (T3), adjusted odds ratio (OR) 1.93, 95% confidence interval (CI) 1.19–3.13, and P = 0.007). In patients with HF, increased TML levels were associated with a composite endpoint of CV death and HF hospitalization during follow-up (T3, adjusted hazard ratio (HR) 1.93, 95% CI 1.27–2.93, and P = 0.002). Increased TML levels indicated a higher risk of CV death, re-hospitalization, and all-cause mortality.ConclusionSerum TML levels were associated with the presence and severity of HF in all subjects. High levels of TML can indicate complications and poor prognosis in HF patients.

Journey from EMPA-REG to CARMELINA to EMPEROR-Preserved

Diabetes mellitus is present in more than two-fifths of the patients suffering from heart failure (HF), with the incidence being more than twice that found in the non-diabetic population. It doubles the risk of hospitalization and increases the risk of fatal outcomes, thus negatively affecting the prognosis in HF patients. The available pharmacological treatment options are limited, particularly in HF with preserved ejection fraction (EF). Empagliflozin is a sodium-glucose transporter-2 inhibitor, which has shown a protective effect against cardiomyocyte dysfunction through various mechanisms. The benefits of empagliflozin has been seen in multiple studies: EMPA-REG (April 2015), EMPRISE (June 18, 2019), EMPIRE-HF (2019), EMPA-AHF-RESPONSE (January 7, 2020), The EMPEROR Reduced (May 28, 2020), The RECEDE-CHF (November 3, 2020), SUGAR-DM (February 9, 2021), and EMPEROR-Preserved (April 26, 2021). Empagliflozin reduced the risk of all-cause mortality, HF hospitalizations, and biomarkers in patients with HF both with reduced and preserved EF in prospective and retrospective studies, regardless of the presence of diabetes. Linagliptin is a DPP-4i that has demonstrated renal safety with potential albuminuria benefits as well. Both these agents in combination have shown favorable effects on elevated blood pressure and intima-media thickness. Unlike some other gliptins, linagliptin was not associated with an increased risk of HF, rather a nominal reduction noted in CARMELINA (January 18, 2018). When added to the standard of care, it reduced the dose of insulin in high-risk diabetic patients with HF. The risk of hypoglycemia is significantly less in patients treated with linagliptin compared with sulfonylurea regimen as seen in CAROLINA (August 21, 2018). Thus, considering the plethora of clinical benefits demonstrated, a combination of empagliflozin and linagliptin in patients of diabetes at high risk of HF may be a suitable option for primary and secondary prevention.

Frailty in older adults with heart disease.

Heart failure prevalence will double in the next 40years and affects more than 10% of persons over the age of 70years in an age-dependent manner. Frailty is an age-associated clinical syndrome defined as adecrease in physiological reserve in situations of stress, such as operations, infections and acute illness based on astate of higher vulnerability. The prevalence is up to 74% in older individuals over the age of 80years or those over 70years old with ahigh burden of comorbidities and chronic diseases. This geriatric syndrome is associated with aworse clinical outcome and higher morbidity and mortality in acute and chronic disease than in age-matched cohorts without this syndrome. In this brief review, the scientific evidence of appropriate tools for diagnosis of frailty in heart failure patients is addressed. Heart failure management in this special group of patients requires aholistic care planning presented here in accordance with pathophysiologic particularities. Aliterature search in PubMed using the terms "heart failure" and "frailty" was carried out and afurther search in the references based on the findings. The diagnosis of frailty should influence the intensity of further diagnostic investigations and medical treatment based on the personal wishes of the patient, reduced organ reserves and general prognosis. The prognosis of heart failure patients remains poor, partially due to the intertwining with frailty. Aclear statement for the use of an appropriate diagnostic tool for frailty and heart failure and specific therapeutic recommendations are presented based on clinical evidence.

Diagnostic potential of a circulating miRNA model associated with therapeutic effect in heart failure

Heart failure (HF), as the leading cause of death, is continuing to increase along with the aging of the general population all over the world. Identification of diagnostic biomarkers for early detection of HF is considered as the most effective way to reduce the risk and mortality. Herein, we collected plasma samples from HF patients (n = 40) before and after medical therapy to determine the change of circulating miRNAs through a quantitative real-time PCR (QRT-PCR)-based miRNA screening analysis. miR-30a-5p and miR-654-5p were identified as the most significantly changed miRNAs in the plasma of patients upon treatment. In consistence, miR-30a-5p showed upregulation and miR-654-5p showed downregulation in the circulation of 30 HF patients, compared to 15 normal controls in the training phase, from which a two-circulating miRNA model was developed for HF diagnosis. Next, we performed the model validation using an independent cohort including 50 HF patients and 30 controls. As high as 98.75% of sensitivity and 95.00% of specificity were achieved. A comparison between the miRNA model and NT-pro BNP in diagnostic accuracy of HF indicated an upward trend of the miRNA model. Moreover, change of the two miRNAs was further verified in association with the therapeutic effect of HF patients, in which miR-30a-5p showed decrease while miR-654-5p showed increase in the plasma of patients after LVAD implantation. In conclusion, the current study not only identified circulating miR-654-5p for the first time as a novel biomarker of HF, but also developed a novel 2-circulating miRNA model with promising potentials for diagnosis and prognosis of HF patients, and in association with therapeutic effects as well.

Prognostic value of nutritional parameters in systolic heart failure with renal dysfunction.

Although it is known that assessment and management of the nutritional status of patients are important for treatment of patients with heart failure (HF), there are currently no established indicators. Therefore, we investigated the effects of nutritional parameters as well as conventional parameters on the prognosis of HF patients. A total of 1954 consecutive HF patients with left ventricular ejection fraction (LVEF) less than 50% were enrolled in this study. Transthoracic echocardiography was performed and conventional parameters for HF patients and parameters to assess nutritional status were measured in all patients. Patients were followed up with a primary endpoint of lethal cardiac events (CEs) for 30.2 months. During the follow-up period, cardiac events were documented in 619 HF patients. The CEs group had a lower level of cholinesterase (201.5U/L vs 265.2U/L, P <0.0001), lower estimated GFR (35.2 ml/min/1.73m2 vs 50.3ml/min/1.73m2, P< 0.0001), and lower Geriatric Nutritional Risk Index (GNRI) (91.9 vs 100.0, P< 0.0001) than those in the non-CEs group. Serum cholinesterase, estimated GFR, and GNRI were identified as significant prognostic determinants in multivariate analysis. ROC analyses revealed cut-off values of serum cholinesterase, estimated GFR, and GNRI of 229U/L, 34.2 ml/min/1.73m2, and 95.6, respectively, for identifying high-risk HF patients. HF patients with serum cholinesterase< 229U/L, estimated GFR<34.3 ml/min/1.73m2, and GNRI< 95.6 had a significantly greater rate of CEs than that in the other patients (P<0.0001). Low serum cholinesterase and low GNRI can predict cardiac mortality risk in systolic HF patients with renal dysfunction.

C73 PICK YOUR THRESHOLD! HOW TO CALCULATE THE ANAEROBIC THRESHOLD TO STRATIFY HEART FAILURE PROGNOSIS: A COMPARISON BETWEEN ABSOLUTE VALUE, PERCENTAGE OF PEAK VO2 OR PERCENTAGE OF PREDICTED MAXIMUM VO2 IN A LARGE MULTICENTER COHORT OF HFREF PATIENTS WHO UNDER

Abstract Background The anaerobic threshold (AT), identifies the moment during a maximal exercise when hyperventilation occurs in response to the introduction of an anaerobic metabolism. Its value is indicative of the subject‘s training and/or health, it can be used to guide training, rehabilitation or to define appropriateness to undergo major thoracic or abdominal surgery, and it is related to heart failure (HF) prognosis. AT can be expressed as absolute value or as the percentage of predicted maximum VO2 (VO2AT%pred). However, it is not uncommon to find papers that refer AT to the peak VO2 value achieved (VO2AT%peak), rather than its predicted value, but a direct comparison of the prognostic power of these different variables is missing. In this work, we aim to compare the risk–identifying ability of the AT value when expressed in these three different ways in a large population of HF patients. This will help identify which is more correct to use in assessing patient prognosis, especially when peakVO2 is not reached appropriately. Methods The population analyzed counts 7746 patients with HF with history of reduced EF (&amp;lt;40%), recruited between 1998 and 2020 within the MECKI score project. All patients underwent a maximal cardiopulmonary exercise test (CPET), executed in using a ramp protocol on an electronically braked cycle ergometer. Results The present study considered 6157 HF patients with identified AT during the CPET, with a median follow up of 1528 days (689–1826). The main characteristics are reported in Figure 1. Figure 2 shows stratification of patients according to these 3 variables divided in tertiles, considering cardiovascular death (combination of cardiovascular death, urgent transplant or LVAD implantation) as an end point. Comparing the AUC of the three variables considered, we found similar values between VO2AT and VO2AT%pred, while the peak VO2AT% value was significantly lower (p &amp;lt; 0.001), as shown in Figure 3A. Moreover VO2AT%pred is the only variable to maintain a comparable ROC to the peakVO2 one, with the others being significantly lower (Figure 3B). Conclusions VO2 at AT should always be expressed as % of predicted maximal VO2 to be reliable in predicting prognosis in HF patients. Moreover, evaluating a sub–maximal exercise, VO2AT%pred is the only variable to maintain a comparable prognostic power to the peakVO2 one.

Skeletal muscle mass metrics as factors in the prognosis of heart failure patients

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): JSPS KAKENHI Grant Background Sarcopenia is a chronic condition that is characterized by the loss of skeletal muscle mass with declining muscle strength and/or performance that occurs gradually with aging. It has been reported that sarcopenia is highly prevalent in patients with heart failure (HF) and is a poor prognostic factor. Therefore, it is important to accurately assess skeletal muscle mass in patients with HF. However, there are no reports that have simultaneously examined different skeletal muscle mass metrics as factors in the prognosis of HF patients. Purpose The purpose of this study is to examine if the different skeletal muscle mass metrics are associated with the prognosis of HF patients. Methods We examined a total of 869 patients with HF, aged ≥20 years (73 [63, 80] years; 537 males), who were admitted to our hospital and participated in an inpatient cardiac rehabilitation program. We used skeletal muscle mass index (SMI) as measured by bioelectrical impedance analysis (BIA), mid-upper arm circumference (MUAC), arm muscle circumference (AMC), and calf circumference (CC) as metrics of skeletal muscle mass. The primary outcome was all-cause deaths, and secondary outcome was HF readmission. To investigate the association between each skeletal muscle mass metric and prognosis, patients were divided into three groups according to the tertiles of SMI, MUAC, AMC, and CC. In addition, cumulative event rates of survival curves, Gray test, and Fine &amp; Gray test were performed to evaluate the prognostic predictive capability. Results Over a median follow-up period of 0.9 years (interquartile 0.4–1.9) years, a total of 80 deaths and 195 HF readmissions occurred in the patients. Cumulative event rates of survival curves and Gray test showed that there was a significant decrease in all-cause mortality and HF readmission in the high MUAC group and high AMC group compared to their respective low groups (P &amp;lt; 0.05). Fine &amp; Gray test after multivariate adjustment showed significantly better prognosis in the high MUAC group and high AMC group compared to their respective low groups (All-cause mortality: high MUAC group, subdistribution hazard ratio [sHR] = 0.42, 95% confidence interval [CI] = 0.20-0.88, P &amp;lt; 0.05; high AMC group, sHR = 0.34, 95%CI = 0.16-0.72 P &amp;lt; 0.05, HF readmission: high MUAC group, sHR = 0.69, 95%CI = 0.47-1.00, P &amp;lt; 0.05; high AMC group, sHR = 0.63, 95%CI = 0.43-0.93, P &amp;lt; 0.05). Conclusion Patients with HF who maintained high MUAC and high AMC had a good prognosis. CC and SMI were not associated with the prognosis of HF patients. This suggests the importance of evaluating MUAC and AMC in HF patients.

Brain natriuretic peptide levels are associated with cycle length average and are different between Ben-Dov and Corra exercise oscillatory ventilation definitions in heart failure patients

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): CAPES e FAPERGS. Background The brain natriuretic peptide (BNP) is a marker of ventricular dysfunction related to severity and prognosis in heart failure patients. Exercise oscillatory ventilation (EOV) is a phenomenon in the ventilatory pattern associated with a worse prognosis in heart failure patients. EOV diagnosis is defined by the interaction among amplitude, cycle length, and the total time of the oscillations. Ben-Dov and Corrà definitions are used to identify EOV-positive cases by different criteria, which may stratify EOV patients with distinct clinical characteristics. Purpose To assess the BPN levels in heart failure patients and to test BNP level correlation with amplitude, cycle length, and total oscillation time according to Ben-Dov and Corrà definitions. Methods Data from 242 cardiopulmonary exercise tests (CPETs) performed between 2011 and 2014 at an Italian heart centre were screened for EOV identification. CPETs were done in a cycle-ergometer with gas exchange analysed breath-by-breath. EOV cases were identified according to the definitions of Ben-Dov and Corrà. Mann-Whitney test was applied to compare BPN levels between the EOV-positive and negative in each definition and between EOV-positive from Ben-Dov and Corrà definitions. Spearman coefficient (rs) evaluated the association between amplitude and length average of the oscillatory cycle, percentage of total oscillation time, and BNP levels in each EOV definition. The BNP levels from EOV-positive identified by Corrà or Ben-Dov definition alone, and from patients who have met the criteria of both definitions were compared by the Kruskal-Wallis test. Results Sixty-seven patients were identified as EOV-positive. From them, 19 were identified exclusively by the Ben-Dov and 26 by Corrà. Twenty-two met the criteria for both definitions. Overall, no difference in EOV prevalence between Ben-Dov and Corrà definitions was found (20.4 vs 24.2%, p = 0.482). EOV-positive identified by the Ben-Dov definition have higher BNP levels than EOV-negative (p &amp;lt; 0.01) and the EOV-positive by Corrà definition (p = 0.025) (Table 1). Spearman correlation showed association just between BNP levels and cycle length average from EOV-positive by the Ben-Dov (rs = 0.566; p &amp;lt; 0.001) and by Corrà (rs = 0.339; p = 0.011) (Figure 1). When analysed by exclusive criteria identification, the BNP levels were higher in EOV-positive identified by Ben-Dov than Corrà (737 [562 to 1,178] vs 276 [221 to 603] pg/mL; p = 0.009). BNP levels in the EOV-positive identified by both definitions (475 [347 to 852] pg/mL) were not different from those identified by the Ben-Dov and Corrà definitions alone. Conclusion EOV-positive identified by the Ben-Dov have higher BNP levels than EOV-negative and the EOV-positive identified by Corrà, alone or not. BNP levels also are associated with the cycle length average, with a higher correlation for the Ben-Dov EOV-positive.

Impact of recurrent acute heart failure hospitalizations on prognosis of heart failure patients

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Hospitalizations for acute heart failure (AHF) are significant events for heart failure (HF) patients (pts) with each hospitalization portending a poor prognosis. Our aim was to compare pts with recurrent AHF admissions to those without and to study the impact of recurrent admissions on overall mortality. Methods Single centre retrospective study that included all pts followed at the HF Clinic of the Cardiology Department that had at least one visit during 2018. All data since their initial follow-up on HF Clinic was considered. Recurrent admissions were defined as 2 or more admissions for AHF in the same year, during the follow-up. Results A total of 138 pts were included (83% male, mean age 61±11years). Dilated cardiomyopathy (65;47%) and ischemic cardiomyopathy (62;45%) were the most frequent aetiologies and most pts had HF with reduced ejection fraction (131;95%). Mean left ventricular ejection fraction (LVEF) was 26±9% and right ventricular dysfunction was present in 27% of the cases. The majority of patients was on NYHA class II (80, 58%). A total of 84 (61%) pts was medicated with inhibitors of the renin-angiotensin system (iRAS), 45 (33%) with angiotensin receptor-neprilysin inhibitor (ARNI), 127 (92%) with beta-blockers (BB) and 116 (84%) with mineralocorticoid receptor antagonists (MRA). Ninety-seven (70%) pts had a cardiac electronic device implanted (47 CRT, 50 ICD). During a median follow-up of 40 months (IQR 32-58), 41 (30%) pts had hospitalizations for AHF and 21 (15%) had recurrent admissions. The median time to the first hospitalization was 16 months (IQR 6-29). Pts with recurrent admissions had a similar comorbidity profile and HF aetiology in comparison to pts with one or none admissions. Considering baseline echocardiographic parameters on first visit, they had a higher mean E/E’ ratio (22±8 vs 14±6, p= .012) and pulmonary systolic artery pressures (52±20 vs 38±14 mmHg, p= .026). No differences were found in LVEF, left ventricular volumes, presence of right ventricular dysfunction or mitral regurgitation. They were less frequently medicated with iRAS or ARNI (81% vs 96%, p=.012) and BB (81% vs 94%, p= .043) and had a higher mean diuretic dosage (87±47 vs 63±43 mg). During the follow-up a total of 31 (22%) pts died, 14 (10%) for cardiovascular reasons. Pts with recurrent AHF admissions were more likely to die from any cause (log rank =.01). On a multivariate analysis, recurrent AHF hospitalizations were an independent predictor of all-cause death (HR 2.4, IC95% 1.1-5.2, p=.03). Conclusion Recurrent AHF hospitalizations are associated with a worse long-term outcome of HF pts. Efforts should be made for an earlier identification of these pts. A higher baseline pulmonary systolic artery pressure and mean E/E’ ratio may identify a higher risk group who benefits from a closer follow-up.

Association between Frequency of Central Respiratory Events and Clinical Outcomes in Heart Failure Patients with Sleep Apnea.

Heart failure (HF) is a progressive cardiac disorder associated with high mortality and morbidity. Previous studies have shown that sleep apnea (SA) is associated with a poor prognosis in HF patients. When HF coexists with SA, both central and obstructive respiratory events often occur. However, few studies have investigated the association between the frequency of central respiratory events coexisting with obstructive events and clinical outcomes in patients with HF and SA. This was a retrospective observational study. Patients with stable HF, defined as a left ventricular ejection fraction of ≤50%, New York Heart Association class ≥ II, and SA (apnea–hypopnea index of ≥15/h on overnight polysomnography) were enrolled. The primary endpoint was a composite of all-cause death and hospitalization for HF. Overall, 144 patients were enrolled. During a period of 23.4 ± 16 months, 45.8% of patients experienced the outcome. The cumulative event-free survival rates were higher in the central SA-predominant group. Multivariate analyses showed that a greater percentage of central respiratory events was associated with an increased risk of clinical outcomes. In patients with HF and SA, the frequency of central respiratory events was an independent factor for all-cause death and hospitalization for HF.

New ESC/EACTS guideline recommendations for the treatment of secondary mitral regurgitation: reflections on the evidence

New <scp>ESC</scp>/<scp>EACTS</scp> guideline recommendations for the treatment of secondary mitral regurgitation: reflections on the evidence

Clinical Impact of Circulating Galectin-3 on Ventricular Arrhythmias and Heart Failure Hospitalization Independent of Prior Ventricular Arrhythmic Events in Patients with Implantable Cardioverter-defibrillators.

Objective For risk stratification of sudden cardiac death in patients with structural heart disease, more precise predictors in addition to left ventricular ejection fraction (LVEF) are clinically needed. The present study assessed the utility of galectin-3 as an independent indicator for the prognosis of heart failure patients with implantable cardioverter-defibrillators (ICD). Methods The study population consisted of 91 consecutive patients who underwent a routine ICD checkup in our ICD outpatient clinic. Circulating galectin-3 was assessed using a commercially available enzyme-linked immunosorbent assay kit. The enrolled patients were prospectively followed. The primary endpoint was defined as the occurrence of appropriate ICD therapy (AIT), and the secondary endpoint was defined as the occurrence of unplanned overnight hospitalization due to decompensated heart failure (dHF). Results During a mean follow-up of 472±107 days, AIT occurred in 18 patients (20%). Unplanned hospitalizations due to dHF were noted in 12 patients (13%). A receiver-operative characteristics analysis demonstrated a sensitivity of 83% and specificity of 68% for AIT occurrences with a galectin-3 cut-off value of 13.1 ng/mL (area under the curve =0.82). A Kaplan-Meier analysis demonstrated that patients with galectin-3 >13.1 ng/mL had significantly higher incidences of AIT as compared to those with lower galectin-3 (log-rank, p<0.001). This significance was also observed in both subgroup analyses with ischemic and non-ischemic etiology. Cox regression demonstrated that higher galectin-3 was an independent predictor of AIT and dHF, even after adjusting for previous arrhythmic events. Conclusion The circulating galectin-3 level can be used as a clinical indicator of subsequent occurrence of ventricular arrhythmic events and decompensated heart failure, regardless of a history of ventricular arrhythmias.