Lower NT-proBNP Levels Research Articles

Comparative analysis of renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitor and mineralocorticoid receptor antagonists in heart failure with mildly reduced ejection fraction

Abstract Background Apart from sodium-glucose co-transporter 2 inhibitors, the efficacy of renin–angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI)j8788 as well as mineralocorticoid receptor antagonist (MRA) in patients with heart failure with mildly reduced ejection fraction remains uncertain. We assessed the association between these medications and outcomes in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Methods Patients with HFmrEF from our university hospital-integrated Medical Database were included. Associations between the medications and cardiovascular mortality/heart failure hospitalization were evaluated using Cox regressions in a 1:1 propensity score-matched cohort. Inverse probability of treatment weighting was employed to balance baseline patient characteristics. Results Of 2584 patients with HFmrEF, 17% received MRA and 43% received RASI/ARNI. Predictors of MRA use included older age, slightly higher ejection fraction, lower NT-proBNP level, and eGFR >60 mL/min/1.73 m^2. Predictors of RASI/ARNI use included higher body mass index, lower NT-proBNP level, normal uric acid level, normal potassium level, and eGFR >60 mL/min/1.73 m^2. MRA use was not associated with a lower risk of cardiovascular death and hospitalization for heart failure (hazard ratio [HR] = 0.89, 95% confidence interval [CI]: 0.78–1.02 and HR = 1.01, 95% CI: 0.94–1.09, respectively). Conversely, RASI/ARNI use was associated with a lower risk of cardiovascular death but not hospitalization for heart failure (HR = 0.82, 95% CI: 0.71–0.94 and HR = 0.995, 95% CI: 0.924–1.07, respectively). Notably, landmark analysis revealed no significant difference in the risk of outcomes when the follow-up duration exceeded two years. Conclusions The effect of MRA on cardiovascular death and hospitalization for heart failure was neutral, whereas RASI/ARNI was associated with a lower risk of cardiovascular death. Our findings suggest that RASi use may be more beneficial than MRA use in patients with HFmrEF.

Idiopathic pulmonary arterial hypertension, associated with connective tissue disease and comorbidities: prognostic differences? Results the Spanish Registry of pulmonary hypertension (REHAP Registry)

Abstract Introduction Idiopathic pulmonary arterial hypertension (iPAH) and associated with connective tissue disease (PAH-SSc) are the most frequent groups of pulmonary arterial hypertension (PAH) but their long-term survival is usually unequal. Comorbidities, increasing in frequency in these patients, show prognostic influences but it is not known whether these differ in both groups of patients. Methods We collected patients diagnosed with iPAH, heritable, associated with drug or toxine exposure and PAH-SSc between 2014 and 2023 from the Spanish Registry of Pulmonary Hypertension. Patients are classifies into iPAH and PAH-SSc. We analyzed baseline characteristics and the distribution of the different comorbidities in the two groups. Survival analyses estimated by Kaplan-Meier analysis using the log-rank test were done according to PAH etiology and comorbidities and Cox proportional hazard analyses were performed to determine the effects of baseline characteristics on survival. Results Seven hundred and fifty-seven patients were selected for this study. The characteristics of the patients are shown in Table 1. Patients with PAH-SSc compared to iPAH were older (62 vs 56 years), more female (81.8% vs 62.4%), had a more favorable hemodynamic profile, TAPSE/sPAP ratio and lower NT-proBNP levels. No differences were found in functional class or 6MWT. We found a higher proportion of patients in a low and intermediate risk profile, according to ESC, in patients with PAH-SSC as opposed to PAHi (46.8/50.9% vs. 29.3/64.5%; p<0.001). Regarding comorbidities, history of smoking (27.1 vs 54%; p<0-001), obesity (17.1 vs 20.7%; p<0.001) and diabetes (9.4 vs 22.1%; p<0.001) are less frequent in PAH-SSc than in iPAH. There are no differences in the rest of the comorbidities studied in the two groups of patients. In a survival analysis, we found no differences between patients with iPAH and PAH-SSc at 7-year follow-up. Patients with ≥ 3 comorbidities had statistically significantly higher mortality (p<0.001) compared to those with 0 or 1-2 comorbidities in both etiologies. There were no differences between 0 and 1-2 comorbidities. (Figure 1). Variables associated with mortality were male sex (HR 1.9, 95% CI 1,28 – 2.8), age (HR 1.04, 95% CI 1.02 – 1.06), the intermediate risk profile (HR 2.64, 95% CI 1.62 – 4.32) and high risk profile (HR 9.97, 95% CI 4.36 – 18.47), but not etiology. The presence of connective tissue diseases, were not associated with increased mortality. Conclusions Patients with PAH-SSc show lower comorbidities, better hemodynamic profile, RV-PA coupling and risk profile than those with iPAH. Comorbidity has a great relevance in survival but without differences according to etiology. The presence of male sex, age, the intermediate and high risk profile is associated with worse survival, but not the connective tissue diseases.

Natriuretic peptides, kidney function and clinical outcomes in heart failure with mildly reduced or preserved ejection fraction: pooled data from the I-PRESERVE, TOPCAT, PARAGON and DELIVER trials

Abstract Background The prognostic utility of N-terminal pro-B-type (NT-proBNP) in patients with heart failure and chronic kidney disease (CKD) is incompletely understood since elevations in NT-proBNP could be related either to decreased clearance by the kidney or to increased severity of structural heart disease. Purpose We sought to assess the association of NT-proBNP with cardiovascular and mortality outcomes in patients with heart failure and mildly reduced or preserved ejection fraction, stratified by baseline kidney function. Methods We conducted a pooled analysis of individual participants with NT-proBNP and estimated glomerular filtration rate (eGFR) measured at baseline in the I-PRESERVE, TOPCAT (Americas region), PARAGON and DELIVER trials. We evaluated the relationship between NT-proBNP and kidney function using piecewise linear regression. Using multivariable Cox and Poisson regression models, we assessed the association of NT-proBNP with clinical outcomes across different levels of eGFR (≥60, 45-<60 and <45 mL/min/1.73m2). The primary outcome was hospitalisation for heart failure or cardiovascular death. Results Among 14,831 participants (mean age 72.1 years, 50.3% female, mean eGFR 63.3 mL/min/1.73m2 and median NT-proBNP 840 pg/mL) followed for a median 33.5 months, there were 3,092 primary outcomes, 2,184 heart failure hospitalisations, 1,465 cardiovascular and 1,049 non-cardiovascular deaths. Participants in lower eGFR categories were more likely to be older, female, and have atrial fibrillation and diabetes (all p<0.001). NT-proBNP levels increased by 9%, 8%, and 23% per 10 mL/min/1.73m2 lower eGFR in patients with baseline eGFR ≥60, 45-60, and <45 mL/min/1.73m2, respectively (P for non-linearity <0.001). For any given NT-proBNP concentration, participants with eGFR <45 mL/min/1.73m2 were at highest risk (Figure 1). Each doubling in NT-proBNP was associated with a 37% relative increase in the primary outcome (HR 1.37, 95% CI 1.34-1.41), consistent across different eGFR categories (P-interaction=0.42). Association between NT-proBNP and other clinical outcomes were also consistent across different levels of kidney function (all P-interaction>0.3; Figure 1). Equivalent risk for the primary outcome was apparent at NT-proBNP levels approximately 2.5- to 3.5-fold lower in patients eGFR <45 mL/min/1.73m2, compared to those with eGFR ≥60 mL/min/1.73m2. (Figure 2). Conclusion NTproBNP is a potent predictor of risk in patients with heart failure with mildly reduced or preserved ejection fraction across the spectrum of kidney function. However, in patients with reduced kidney function, lower NT-proBNP levels confer absolute risk of cardiovascular outcomes similar to substantially higher NT-proBNP levels in patients with normal kidney function. Accordingly, interpretation of NTproBNP levels should vary according to kidney function, particularly in those with eGFR <45 mL/min/1.73m2.

The Influence of Adherence to a Mediterranean Diet on Decompensation in Patients with Chronic Heart Failure.

Chronic heart failure (CHF) is a major health problem, representing the main cause of hospitalization in people over 65 years of age. Several studies have associated the Mediterranean diet with a cardioprotective function, improving prognoses in patients with high cardiovascular risk. Our main objective is to determine whether higher adherence to the Mediterranean diet is associated with a lower severity of CHF, based on the number of decompensations and disease complications. This study was a single-center retrospective cohort study conducted at the Virgen del Rocío Hospital (Seville). Adherence to a Mediterranean diet was determined by the Mediterranean Diet Adherence Screener (MEDAS) in patients with chronic heart failure in a state of clinical stability, the number of decompensations in the 12 months before inclusion, cardiac biomarkers (NT-proBNP and CA125), evaluation of dyspnea, and quality of life assessment according to NYHA and KCCQ scales and analytical profiles. Seventy-two patients were included (35 with high adherence to the Mediterranean diet and 37 with low adherence). The mean age was 81.29 ± 0.86 years. A trend towards fewer decompensations (1.49 ± 0.14 vs. 1.92 ± 0.17, p = 0.054) and lower NT-proBNP values (2897.02 ± 617.16 vs. 5227.96 ± 1047.12; p = 0.088) was observed in patients with high adherence compared to those with low adherence to the Mediterranean diet. Our results suggest that patients with CHF and high adherence to the Mediterranean diet have a tendency towards an improved cardiac profile, indicated by fewer decompensations and lower NT-proBNP levels. Future clinical trials are needed to substantiate these hypotheses.

Changes of clinical characteristics, distribution of red flags and prognosis in contemporary patients with wild-type transthyretin amyloidosis cardiomyopathy

Aim Increased diagnostic awareness and specific disease treatments have changed the landscape of transthyretin cardiac amyloidosis (ATTR). Patients with wild-type ATTR (ATTRwt) are increasingly being diagnosed, potentially changing the clinical profile and prognosis compared with existing retrospective data. We aimed to study the clinical characteristics, distribution of red flags and prognosis of contemporary ATTRwt patients. Methods From January 1st 2017, to December 31st 2022, 213 consecutive patients were diagnosed with ATTRwt and prospectively followed up. Data on clinical characteristics, biomarkers, echocardiography findings, hospitalization due to worsening heart failure (WHF) and all-cause mortality were collected. Results A 37% increase in newly diagnosed patients from 2017–2019 (n = 90) vs. 2020–2022 (n = 123) was observed. The majority of patients presented with NAC disease stage I in the latter period (49% in 2017–2019 vs. 58% in 2020–2022, p = .16). Red flags were primarily cardiac-related, including elevated NT-proBNP, impaired left ventricular longitudinal systolic strain with an apical sparing pattern, heart failure with increased left ventricular wall thickness and elevated troponins. NAC disease stage I as well as low NT-proBNP levels (<1000 ng/L) were significantly associated with better survival (both p < .001). When compared with NAC disease stage II + III combined, patients with NAC disease stage I had a significantly lower risk of WHF hospitalization or death (log rank test: p = .0001). Independent predictors of the combined endpoint WHF hospitalization or death were NT-proBNP (HR 1.03 [95% CI 1.00–1.07], p < .049) and prior implantation of permanent pacemaker (HR 2.01 [1.30–3.11], p = .002). Conclusion Increased diagnostic awareness resulted in a 37% increase in newly diagnosed patients in 2020–2022 vs. 2017–2019. As expected all-cause mortality but also the morbidity in terms of risk of hospitalization with WHF were significantly lower in patients with NAC disease stage I, as well as in those with low NT-proBNP levels <1000 ng/L. These findings underline the importance of continuous attention to diagnostic awareness, as early diagnosis is critical for initiating both general and specific ATTR treatment, thus improving prognosis.

N-terminal pro-B-type natriuretic peptide levels vary by ethnicity and are associated with insulin sensitivity after gestational diabetes mellitus

BackgroundIndividuals of South Asian origin have a greater risk of cardiovascular disease after gestational diabetes mellitus (GDM) than European individuals. B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-proBNP) are commonly used for heart failure screening and diagnosis, but biologically BNP exerts several beneficial cardiovascular effects primarily by counteracting the renin-angiotensin-aldosterone-system. We asked whether ethnic differences in circulating NT-proBNP levels could be explained by the differences in cardiometabolic and inflammatory risk markers?MethodsWe examined 162 South Asian and 107 Nordic women in Norway 1–3 years after GDM with a clinical examination, fasting blood samples and an oral glucose tolerance test. We measured the levels of NT-proBNP, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), leptin, adiponectin and markers of insulin sensitivity, such as the Matsuda insulin sensitivity index (ISI). Finally, we tried to identify which independent covariate best mediated the ethnic differences in NT-proBNP.ResultsThe mean (SD) age was 35.3 (4.5) years, BMI 29.1 (6.0) kg/m2, waist-height ratio 0.60 (0.08) and 164 women (61%) had prediabetes/diabetes. Notably, South Asian women had lower levels of NT-proBNP than Nordic women in both the normoglycemic and prediabetes/diabetes groups (median (IQR) 26 (15–38) vs. 42 (22–66) ng/L, p < 0.001). Higher NT-proBNP levels were associated with greater insulin sensitivity in both South Asian and Nordic women (p = 0.005 and p < 0.001). South Asian women had higher levels of hsCRP (median (IQR) 2.2 (1.1–4.4) vs. 1.2 (0.3–4.2) mg/L), IL-6 (2.3 (1.5–3.2) vs. 1.5 (1.5–2.5) pg/mL), leptin (1647 (1176–2480) vs. 1223 (876–2313) pmol/L), and lower adiponectin levels (7.2 (5.3–9.3) vs. 10.0 (7.2–13.5) mg/L) and Matsuda ISI (2.4 (1.7–3.7) vs. 4.2 (2.9–6.1), pall<0.01) than Nordic women. Even after adjusting for these differences, higher NT-proBNP levels remained associated with insulin sensitivity (22% higher NT-proBNP per SD Matsuda ISI, p = 0.015). Insulin sensitivity and adiponectin mediated 53% and 41% of the ethnic difference in NT-proBNP.ConclusionsNT-proBNP levels are lower in South Asian than in Nordic women after GDM. Lower NT-proBNP levels correlate with impaired insulin sensitivity. Lower NT-proBNP levels in South Asian women could, therefore, be attributed to impaired insulin sensitivity rather than total body fat.

Lower Levels of NT-proBNP in Pacific Peoples With Heart Failure

Lower Levels of NT-proBNP in Pacific Peoples With Heart Failure

N terminal pro-brain natriuretic peptide level and benefits of chronic total occlusion revascularization

BackgroundThe management of revascularization of chronic total occlusions (CTOs) remains controversial. Whether specific patients gain survival benefit from CTO revascularization remains unknown. ObjectivesWe investigated whether (i) patients with CTO have higher N terminal pro-brain natriuretic peptide (NT pro-BNP) levels than patients without CTO, (ii) in patients with CTO, NT pro-BNP levels predict adverse events, and (iii) those with elevated levels benefit from revascularization. MethodsIn 392 patients with stable, significant coronary artery disease (CAD) and CTO undergoing coronary angiography, rates of all-cause mortality, cardiovascular death, and a composite (cardiovascular death, myocardial infarction and heart failure hospitalizations) were investigated. Unadjusted and adjusted Cox proportional and Fine and Gray sub-distribution hazard models were performed to determine the association between NT pro-BNP levels and incident event rates in patients with CTO. ResultsNT pro-BNP levels were higher in patients with, compared to those without CTO (median 230.0 vs. 177.7 pg/mL, p ≤0.001). Every doubling of NT pro-BNP level in patients with CTO was associated with a > 25% higher rate of adverse events. 111 (28.5%) patients underwent CTO revascularization. In patients with elevated NT pro-BNP levels (> 125 pg/mL), those who underwent CTO revascularization had substantially lower adverse event rates compared to patients without CTO revascularization (adjusted cardiovascular death hazard ratio 0.29, 95% confidence interval (0.09–0.88). However, in patients with low NT pro-BNP levels (≤ 125 pg/mL), event rates were similar in those with and without CTO revascularization. ConclusionNT pro-BNP levels can help identify individuals who may benefit from CTO revascularization.

Patients with acute decompensation of heart failure and and low natriuretic peptide levels

Abstract Funding Acknowledgements None. Background Nt-proBNP is frequently used in the diagnosis of acute decompensated heart failure (ADHF). However, there are some patients that although they have the clinical features of ADHF present with paradoxically low Nt-proBNP levels. Purpose To record the clinical and epidemiological characteristics of patients presenting with ADHF and low Nt-proBNP levels and compare them with those patients with high Nt-proBNP levels. Methods We retrospectively analyzed the data from the patients admitted with ADHF in our department, for a period of 2 years and divided them in 2 groups : low Nt-proBNP group (BNP&amp;lt;300 pg/ml) and high Nt-proBNP group (&amp;gt;300pg/ml). We recorded the clinical and epidemiological characteristics, the laboratory findings as well as the treatment they received. Results We recorded 636 patients admitted due to ADHF. 512 (80.5%) were in the high Nt-proBNP group and 124(19.5%) in the low Nt-proBNP group. Patients in the low Nt-proBNP group had more frequently BMI&amp;gt;25 (low Nt-proBNP vs high Nt-proBNP group) (65% vs 32%, p&amp;lt;0.01), and were more often females (71% vs 39%, p&amp;lt;0.05). In terms of heart failure classification, the low Nt-proBNP group had more often preserved ejection fraction (66% vs 42%, p&amp;lt;0.01) whereas in HFrEF (22% vs 39%) and HFmrEF (19% vs 12%) we did not notice any significant difference. Regarding age, less patients in the low Nt-proBNP group were older than 65 years old (62% vs 87%, p&amp;lt;0.05). The low Nt-proBNP group patients stayed longer in the hospital (9.2±2.4 days vs 6.6±3.7 days, p&amp;lt;0.01) needed smaller doses of furosemide (60±12,8 mg/d vs 180±24.2 mg/d, p&amp;lt;0.01) and more rare vasopressor (37% vs 42%) or inotropic (27% vs 56% , p&amp;lt;0.05) support. On the contrary, they needed more often non invasive ventilation (NIV) (73% vs 42%, p&amp;lt;0.05). As far as the laboratory findings is concerned, the low Nt-proBNP group presented with lower high sensitivity troponin I (hsTnI) levels (56±17.9 pg/ml vs 127±36.2 pg/ml, p&amp;lt;0.01) and higher GFR (96±12.2 mL/min/1.73 m² vs 45±23.7 mL/min/1.73 m², p&amp;lt;0.05). Conclusions Patients admitted with ADHF and low Nt-proBNP levels seem to be younger, females, with higher BMI and more often with preserved ejection fraction. It seems that they need more frequently non invasive ventilation , smaller doses of diuretics and require more days in the hospital. More studies are needed to identify the characteristics of this subset of patients that could lead to more effective management.

Association between antioxidant metabolites and N-terminal fragment brain natriuretic peptides in insulin-resistant individuals.

Oxidative stress plays a pivotal role in the development of metabolic syndrome, including heart failure and insulin resistance. The N-terminal fragment of brain natriuretic peptide (NT-proBNP) has been associated with heightened oxidative stress in heart failure patients. Yet, its correlation with insulin resistance remains poorly understood. Our objective is to investigate the association between oxidative stress markers and NT-proBNP levels in insulin-resistant individuals. In this cross-sectional study involving 393 participants from the Qatar Biobank, clinical and metabolic data were collected, and the association between NT-proBNP and 72 oxidative stress metabolites was compared between insulin-sensitive and insulin-resistant individuals. Our results showed significantly lower NT-proBNP levels in insulin-resistant individuals (median = 17 pg/ml; interquartile range = 10.3-29) when compared to their insulin-sensitive counterparts (median = 31 pg/ml; interquartile range = 19-57). Moreover, we revealed notable associations between NT-proBNP levels and antioxidant metabolic pathways, particularly those related to glutathione metabolism, in insulin-resistant, but not insulin-sensitive individuals. The significant decrease in NT-proBNP observed in individuals with insulin resistance may be attributed to a direct or indirect enhancement in glutathione production, which is regarded as a compensatory mechanism against oxidative stress. This study could advance our understanding of the interplay between oxidative stress during insulin resistance and cardiovascular risk, which could lead to novel therapeutic approaches for managing cardiovascular diseases. Further investigations are needed to assess the practical utility of these potential metabolites and understand the causal nature of their association with NT-proBNP in the etiology of insulin resistance.

Real life experience of tafamidis for the treatment of Spanish patients with Val30Met transthyretin amyloidosis with polyneuropathy

IntroductionTafamidis is the only approved transthyretin stabiliser approved for the treatment of variant transthyretin amyloidosis (A-ATTRv) related polyneuropathy (PNP). The aim of this study is to analyse the effectiveness of tafamidis in a real-world setting in Spain. MethodsThis is a national multicenter study in which patients with V30M A-ATTR related PN treated with tafamidis for at least 1 year were included. Clinical, demographic, analytical and neurophysiological variables were analysed. Results100 patients were recruited. Overall, 47 patients (47%) were classified as complete responders, 32 (32%) as partial responders and 21 (21%) as non-responders. The median duration of treatment with tafamidis was 35 months. Better treatment response was shown in patients with in polyneuropathy disability score (PND) I, lower neuropathy impairment score (NIS), compound muscle action potential (CMAP) and Norfolk QoL questionnaire. Higher albumin levels and lower NTproBNP levels were also associated with better treatment response. A basal NIS≥15 predicts that the patient could be a non-responder with a 60% probability. ConclusionsOur results reinforce the tafamidis efficacy to treat A-ATTRv-PNP if started early in the disease course. Patients with the V30M variant, NIS<15 and PND I are the most appropriate subjects for this treatment.

Association of NT-proBNP and sST2 with Left Ventricular Ejection Fraction and Oxidative Stress in Patients with Stable Dilated Cardiomyopathy.

The aim of this study was to analyze the relationship between levels of sST2, NT-proBNP and oxidative stress markers in patients with reduced ejection fraction (HFrEF) due to non-ischemic cardiomyopathy. A total of 88 patients with HFrEF were divided into four groups based on left ventricular ejection fraction (≤25% and >25%) and NYHA functional class (group 1-LVEF > 25% and NYHA class I or II; group 2-LVEF > 25% and NYHA class III or IV; group III-LVEF ≤ 25% and NYHA class I or II; group IV-LVEF ≤ 25% and NYHA class III or IV). In 39 (44.32%) patients LVEF was reduced below 25%, and 22 of them (56.41%) were in NYHA functional class III/IV. Of the 49 (55.68%) patients with LVEF ≥ 25%, only 18.37% were in NYHA functional class III/IV (p < 0.001). Patients with LVEF ≥ 25% had lower levels of NT-proBNP, total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI). The levels of NT-proBNP but not sST-2 correlated positively with NYHA functional class (p < 0.001) and negatively with LVEF (p < 0.001). The levels of sST-2 were associated with increased TAC (p = 0.009) and uric acid (p = 0.040). These findings indicate that only NT-proBNP was related to the severity of heart failure, whereas sST2 correlated with total antioxidant capacity. Therefore, in stable patients with HFrEF due to dilated cardiomyopathy, sST2 may be an additional biomarker reflecting the redox status, but not the severity of heart failure.

Baseline NT-proBNP levels as a predictor of short-and long-term prognosis in COVID-19 patients: a prospective observational study

BackgroundUp to 20% of COVID-19 patients can suffer COVID-19-related myocardial injury. Elevated cardiac biomarkers, such as hs-cTnT and NT-proBNP, have been related to worse short-term prognosis. However, data on NT-proBNP and long-term prognosis are scarce. We have evaluated the potential association of baseline age-adjusted NT-proBNP levels and outcomes at one-year follow-up in COVID-19 patients.MethodsThis was a single-center prospective study of 499 COVID-19 patients in whom NT-proBNP was assessed at hospital admission. NT-proBNP levels were age-adjusted and patients were classified as high or low NT-proBNP. Clinical and demographic characteristics, comorbidities, laboratory results, and in-hospital complications and mortality were compared between the two groups. Survivors of the acute phase of COVID-19 were followed up for one year from admission to detect readmissions and mortality.ResultsThe 68 patients with high NT-proBNP levels at hospital admission were older, with more cardiovascular risk factors, cardiovascular disease, comorbidities, myocardial injury, and higher levels of inflammatory markers than patients with low NT-proBNP levels. They also had more in-hospital complications and a higher acute-phase mortality rate (60.3% vs. 10.2%, p < 0.001). High NT-proBNP levels were an independent marker of death during hospitalization (HR 1.95; CI 1.07–3.52). At one-year follow-up, high NT-proBNP levels were independently associated with mortality (HR 2.69; CI 1.47–4.89). Among survivors of the acute phase of COVID-19, there were no differences in hospital readmissions between those with high vs. low NT-proBNP levels, but survivors with high baseline NT-proBNP levels showed a higher 1-year mortality rate (7.4% vs. 1.3%, p = 0.018).ConclusionsHigh age-adjusted NT-proBNP levels at the time of hospital admission for COVID-19 are associated with poor short and long-term prognosis. High NT-proBNP seems also to be related to worse prognosis in survivors of the acute phase of COVID-19. A closer follow-up on these patients may be crucial.

Heart failure patients without echocardiography are more commonly diagnosed in hospital care and are associated with higher mortality compared to primary care

Objective This Swedish study aimed to assess the prevalence, associated clinical factors, and mortality rates of heart failure patients diagnosed without echocardiograms in both hospital and primary care settings. Design We conducted a retrospective population-based study using data from the Region Halland healthcare database in Sweden covering 330,000 residents. Subjects From 2013–2019, 3,903 patients received an incidental heart failure diagnosis without an echocardiogram and they were followed for one year. Main outcome measures Using logistic and Cox regression analyses, we evaluated the prevalence, clinical characteristics, and all-cause mortality at intervals of 30, 100, and 365 days post-diagnosis. Results In this Swedish cohort, the one-year all-cause mortality rate was markedly higher for patients diagnosed in hospitals (42%) compared to those in primary care (20%, p < 0.001). Patients diagnosed in primary care were older and had fewer comorbidities and lower NT-proBNP levels. Hospital-diagnosed patients faced a significantly higher mortality rate in the initial 30 days but saw similar rates to primary care patients thereafter. Conclusion In a Swedish region, heart failure diagnoses without echocardiograms were more common in hospitals, and these patients initially faced worse prognoses. After the first month, however, the prognosis of hospital-diagnosed patients mirrored that of those diagnosed in primary care. These findings emphasize the need for improved diagnostic and treatment approaches in both care settings to enhance outcomes.

Abstract 16832: Biomarker Enhanced Risk Prediction of Incident Heart Failure in Low-Risk Patients: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Primary prevention strategies to reduce heart failure (HF) burden are urgently warranted. The Pooled Cohort equations to Prevent HF (PCP-HF) risk score is a validated risk tool that integrates readily available parameters obtained in primary care setting to estimate the 10-year risk for incident HF. Although PCP-HF performs well for high-risk individuals, the model’s predictive utility for low-risk individuals may potentially be enhanced by integration of biomarkers. Methods: In this study, the PCP-HF risk score was derived from data collected at visit 5 (2011-2013) of the ARIC cohort study and its 5-year predictive accuracy was investigated using surveillance data up to 2019. Participants with &lt;10% PCP-HF risk probability of incident HF were classified as low-risk. Incremental improvement in predicting incident HF by including laboratory and imaging-based biomarkers in the low-risk population was analyzed by logistic regression, by calculating the area under the curve (AUC) from receiver operating characteristics. Results: Of 4980 study participants with 5 years of follow up, 47% had a low PCP-HF risk score (mean age 73 years, 71% women, 32% Black). Of these, 3% developed HF within 5 years. Compared to those with a high PCP-HF risk score, individuals with low PCP-HF risk score were younger, more often female and Black; had lower left ventricular (LV) mass index and left atrial volume index, higher magnitude of LV global longitudinal strain, and lower levels of NT-proBNP and hs-TnT. On further analysis, the model incorporating laboratory and imaging-based biomarkers exhibited greater predictive accuracy for incident HF compared to the original PCP-HF risk score in this low-risk population (AUC: 0.85 vs 0.62). Conclusion: The integration of laboratory and imaging-based biomarkers with the PCP-HF risk score enhances the predictive accuracy of risk modeling for incident HF, especially in individuals identified as low-risk by the 10-year risk prediction tool.

Abstract 15501: Effects of Vericiguat on Right Ventricular Function in Chronic Heart Failure Patients

Introduction: Despite the beneficial clinical effects of vericiguat in chronic heart failure, the potential effects of vericiguat therapy on right ventricular (RV) function remain poorly defined. Hypothesis: We sought to evaluate the effects of vericiguat on RV function in chronic heart failure patients. Methods: We performed a prospective non-randomized single center study enrolling 24 consecutive HFrEF outpatients who were receiving stable heart failure therapy for at least 3 months. All patients received vericiguat 2,5 mg qd at baseline and up-titration was performed on a bi-weekly basis to the target dose of 10 mg qd. At baseline and at 3 month follow-up all patients underwent clinical, biochemical and echocardiographic evaluation. Improved RV function was defined as any improvement in TAPSE between baseline and 3 months. Results: During follow-up we observed a significant overall improvement of TAPSE (18.5±4.2 mm vs. 21.3±4.7 mm; P=0.03) and TR gradient (35±10 mmHg vs. 29±8 mmHg; P=0.04). RV function improved in 17 patients (70%; Group A) and remained unchanged in 7 (30%) patients (Group B). At baseline, the two groups did not differ in gender (male; 100% in Group A vs. 90% in Group B; P=0.37), age (64±9 years vs. 61±9 years; P=0.59), NYHA class (2.9±0.5 vs. 3.1± 0.3; P=0.39), or heart failure etiology (ishemic: 64% vs. 71%; P=0.76). Heart failure therapy was also comparable: ARNI (94% vs. 100%; P=0.53), beta blockers (94% vs. 100%; P=0.53), MRA (100% vs. 100%), SGLT2i (100% vs. 86%; P=0.12) and loop diuretics (59% vs. 57%; P=0.94). We found no differences in baseline LVEF (30±6% vs. 29±4%; P=0.73), LVOT VTI (15±3 cm vs. 14±5 cm; P=0.34), LVEDV (219±51 mL vs. 197±56 mL; P=0.39), TAPSE (17±3 mm vs. 18±3; P=0.68), RVIDd (39±4 mm vs. 38±3 mm; P=0.58) and TR gradient (34±8 mmHg vs. 38±11 mmHg; P=0.38). Both groups received similar doses of vericiguat (8.5±2.8 mg in Group A vs. 6.8±2.9 mg in Group B; P=0.19). Compared to Group B, we found significantly lower baseline NT-proBNP serum levels in Group A (1888±1973 pg/mL vs. 6373±5465 pg/mL; P=0.009). Conclusions: Vericiguat therapy may be associated with improved RV function in chronic heart failure patients. The effects appear to be particulary pronounced in patients with lower NT-proBNP levels.

Abstract 18306: Race, Natriuretic Peptides, and Physiological Perturbations

Introduction: Racial differences in natriuretic peptide (NP) levels among young adults are uncharacterized. Race-based differences in NP response to physiological and pharmacological perturbations are unknown. Methods and Results: A population-level study in healthy young individuals (18-40 years) with NT-proBNP measurements from the 1999-2004 National Health and Nutrition Examination Survey cycles was conducted. In this study of 3055 individuals, Blacks [34.3% (29.3-38.9%)] had lower NT-proBNP levels compared with Whites. Healthy participants were recruited in 2018-23 in a mechanistic trial to assess the racial differences in NP response to standardized exercise and 6 weeks of metoprolol (started at 50 mg/day and doubled every 2 weeks). MR-proANP was measured pre- and post-exercise, before starting metoprolol and then every 2 weeks till study completion. Among 72 young adults [39 (54.2%) White, 37 (51.4%) females], the increase in MR-proANP levels was higher in Whites [49.0% (38.2-60.6%) compared with Blacks [35.9% (25.2-47.6%)] after exercise (p int : 0.004). With metoprolol, MR-proANP levels increased by 36.3% (23.3-50.8%) in Whites and 28.3% (15.0-43.0%) in Blacks (p int :0.42). To assess the mechanism of ANP increase, iPSC-CM (3 controls and 3 experiments) were treated with metoprolol to assess the change in NPPA expression. miR-425 (negative regulator of ANP) levels were measured at the abovementioned time points. The expression of NPPA in iPSC-CM did not change on treatment with metoprolol. With metoprolol, the relative expression of miR-425 reduced by ~10% at the end of 6 weeks. Conclusion: Using multiple lines of evidence, this study established that healthy young Blacks have lower NP levels and have a blunted NP response to exercise compared with Whites. ANP protein levels differed but no changes in ANP expression were noted with metoprolol. Further work is needed to elucidate pathways underlying miR-425 expression responsiveness with metoprolol.

Left atrial strain superior to structural remodeling in identifying occult atrial fibrillation.

Occult atrial fibrillation (AF) is a significant risk factor for occult stroke but is difficult to detect. Myocardial strain, based on speckle tracking echocardiography (STE), can detect subclinical changes in left atrial (LA) function. This study aimed to investigate the diagnostic value of LA strain in identifying asymptomatic AF patients with normal electrocardiograms and healthy volunteers. A total of 354 subjects were retrospectively enrolled. Patients were divided into two groups based on whether they had AF during echocardiography. Patients with sinus rhythm during echocardiography were further divided into healthy control group and occult AF group. Patients with AF during echocardiography were further divided into paroxysmal AF group and persistent AF group. LA mechanical function measured by STE was compared between patients with asymptomatic AF and volunteers. Conventional echocardiographic indicators were measured. The diagnostic value of LA strain for identifying asymptomatic AF was assessed by univariate and multivariate regression analysis and receiver operating characteristic (ROC) curves. Occult AF patients had higher NT-proBNP levels, larger RA area, larger LAVmax and decreased LAEF than control group. However, occult AF patients had lower NT-proBNP levels, RA area and LAVmax and higher LAEF than paroxysmal and persistent AF. The measured LA reservoir strain (LASr), LA conduit strain (LAScd), LA contraction strain (LASct) of occult AF group was significantly lower than that of control group. However, occult AF patients had preserved LAScd and LASct than paroxysmal and persistent AF. RA area, LAEF and LASr were remarkable correlation with occult AF after adjustment for NT-proBNP, LAVmax, and LAScd. The area under curve of ROC for LASr was the greatest among RA area, LAEF and LASr, with a cut-off value of 34.1% (sensitivity: 75.4%, specificity: 87.6%). LASr can identify occult AF in the asymptomatic population. Patients with LASr values ≤34.1% have a higher incidence of occult cardiac dysfunction. These findings help identify patients with occult AF and further risk stratification for the AF population.

Associations between diet quality and NT-proBNP in U.S. adults, NHANES 1999-2004

ObjectiveN-terminal pro-brain-type natriuretic peptide (NT-proBNP) is a marker of cardiac wall stress and is a predictor of cardiovascular disease. Higher diet quality is associated with lower risk of cardiovascular disease. The association between diet quality and subclinical cardiovascular disease assessed by NT-proBNP is uncharacterized. We investigated the associations between diet quality, using Healthy Eating Index-2015 (HEI-2015), and NT-proBNP from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. MethodsWe included 9,782 adults from NHANES 1999-2004 without self-reported cardiovascular disease. The HEI-2015 ranges from 0 to 100, with higher scores indicating better diet quality. The HEI-2015 was categorized into sex-specific quintiles. Regression models were used to quantify associations between the overall HEI-2015 score and its 13 components with log-transformed NT-proBNP. The beta coefficients were converted to percent differences. ResultsAmong 9,782 participants, mean age was 45 years, 48% were men, and 72% were non-Hispanic White adults. After adjusting for sociodemographic characteristics, lifestyle factors, and medical history, those in the highest vs. lowest HEI-2015 quintile had an 8.5% (95% CI: -14.6% to -2.0%) lower NT-proBNP level. There was a dose-response association between HEI-2015 and NT-proBNP (P value for trend = 0.01). Each 1-unit higher in sodium and added sugars score indicating lower intake was associated with lower NT-proBNP by 7.7% (95% CI: -12.8% to -2.2%) and 6.5% (95% CI: -12.0% to -0.7%), respectively. ConclusionHigher diet quality, especially lower intakes of sodium and added sugars, was associated with lower serum levels of NT-proBNP.

Accelerometer-derived physical activity and sedentary time and cardiac biomarkers: The Maastricht Study.

Cardiac troponins and NT-proBNP are biomarkers of cardiac injury that are used clinically in the diagnosis of myocardial infarction and heart failure. It is not known whether the amount, types and patterns of physical activity (PA) and sedentary behaviour are associated with levels of cardiac biomarkers. In the population-based Maastricht Study (n = 2,370, 51.3% male, 28.3% T2D) we determined cardiac biomarkers hs-cTnI, hs-cTnT, and NT-proBNP. PA and sedentary time were measured by activPAL and divided into quartiles [quartile 1 (Q1) served as reference]. The weekly pattern of moderate-to-vigorous PA (insufficiently active; regularly actives; weekend warriors) and coefficient of variation (CV) was calculated. Linear regression analyses were conducted with adjustment for demographic, lifestyle, and cardiovascular risk factors. There was no consistent pattern between physical activity (different intensities: total, light, moderate-to-vigorous and vigorous) and sedentary time on the one hand and hs-cTnI and hs-cTnT on the other. Those with the highest levels of vigorous intensity PA had significantly lower levels of NT-proBNP. With regard to PA patterns, weekend warriors and regularly actives had lower levels of NT-proBNP but not with hs-cTnI and hs-cTnT (reference:insufficiently actives). A higher weekly moderate-to-vigorous PA CV (indicating more irregular activity) was associated with lower levels of hs-cTnI and higher levels of NT-proBNP, but not with hs-cTnT. In general, there was no consistent association between PA and sedentary time and cardiac troponins. In contrast, vigorous and possibly moderate-to-vigorous intensity PA, especially if done regularly, were associated with lower levels of NT-proBNP.