Higher Natriuretic Peptide Levels Research Articles

The Balance Between the Natriuretic Peptides and the Renin-Angiotensin-Aldosterone System in the Preservation of Ideal Cardiovascular Health.

A healthy lifestyle plays a key role for maintaining the cardiovascular health (CVH) status and prevent cardiovascular disease occurrence. In fact, a healthy lifestyle was included in the AHA Cardiovascular Health score (Life's Simple 7 [LS7]), subsequently updated to Life's Simple 8 [LS8]. Apart from the importance of controlling conventional cardiovascular risk factors, increasing evidence supports the contributory role of cardiovascular hormones. Higher levels of natriuretic peptides (NPs) and lower levels of renin and aldosterone were significantly associated to CVH. NT-proBNP levels showed a direct relationship with CVH scores in large general Caucasian populations, being also a marker of CVH changes and a predictor of future adverse events. On the other hand, renin and aldosterone were inversely related to CVH scores. In contrast, the counter-regulatory angiotensins [Ang (1-7) acting through Mas receptor, Ang (1-9) acting through Angiotensin Type 2 receptor, and alamandine] strengthen the beneficial properties of NPs. This evidence can be explained by both the effects on systemic hemodynamic and possible pleiotropic local functions regulating different pathways involved in the maintenance of CVH. Based on the current evidence, circulating levels of NT-proBNP, renin and aldosterone may affect CVH in apparently asymptomatic individuals and represent additional markers of residual cardiovascular risk.

Clinical profile of an unselected population with heart failure treated with vericiguat in real life: differences with the VICTORIA trial.

Vericiguat, an oral stimulator of soluble guanylate cyclase, reduces cardiovascular mortality and hospitalisations in patients with heart failure (HF) and reduced ejection fraction, as demonstrated in the VICTORIA trial. This study assessed the real-world use of vericiguat. This cross-sectional, prospective and multicenter registry (VERISEC) included 776 patients from 43 centres in Spain between December 2022 and October 2023. Of these patients, 79.6% were male, with a mean age of 72.4 (SD:8.7) years. Patients in VERISEC were older and had more comorbidities (diabetes, advanced chronic kidney disease) compared to VICTORIA, with 20% having an estimated glomerular filtration rate below 30 ml/min. They also had higher natriuretic peptide levels [NT-proBNP: 3551 (IQR: 1,675.9, 7,054.0)] pg/ml. Most patients (79.8%) started vericiguat after HF decompensation within the previous three months, with high use of loop diuretics (with an average dose of 65 mg/day) and implanted devices (50%). Sixty percent of patients were on quadruple therapy, with a higher use of sodium-glucose co-transporter 2 inhibitors compared to the VICTORIA trial. Despite the more severe disease in the VERISEC cohort, the implementation of guideline-directed medical therapy was greater than in VICTORIA, although vericiguat was initiated at lower blood pressure levels. Patients in the VERISEC registry had more severe illness and higher comorbidities compared to those in the VICTORIA, despite receiving optimised treatments. Further research is needed to identify which patients may benefit the most from vericiguat treatment.

Knowledge of Illness Trajectory and Symptoms of Heart Failure in Patients with Acute Coronary Syndrome.

Preventive management of heart failure (HF) should involve strategies to increase awareness of HF in patients with pre-HF and those at risk of HF. However, the perception of HF in patients with acute coronary syndrome (ACS) remains unclear. This study aimed to assess patient understanding of the definition of HF for the public (i.e., its illness trajectory [intermittent decline], impact on life expectancy [HF would limit life expectancy], and symptoms [shortness of breath, swelling]) that was introduced by the Japanese Circulation Society. This cross-sectional questionnaire-based study enrolled 209 emergently admitted patients with ACS who underwent a cardiac rehabilitation program at a single university-based hospital. We identified the clinical characteristics of patients who understood HF definition. Among the enrolled patients (median age, 69 years; males, 81.3%; 59.8% with ST-elevation myocardial infarction), 64.0% and 53.1% chose the correct answers regarding HF illness trajectory and impact on life expectancy, respectively. While 92.3% of the patients correctly chose shortness of breath as a HF symptom, 56.7% correctly chose swelling. Patient understanding of the definition of HF was associated with younger age, but not with HF risk (i.e., hypertension, diabetes, higher natriuretic peptide levels, lower left ventricular ejection fraction) and history of symptomatic HF. Among patients with ACS who participated in the cardiac rehabilitation program in this cohort, patient understanding of HF definition was suboptimal. Effective measures to improve their understanding should be considered to enhance the prevention of HF.

Associação entre peptídeos natriuréticos e gravidade clínica em pacientes internados por insuficiência cardíaca descompensada

This study aims to associate the values of natriuretic peptides (NP), BNP, and NT-proBNP, with the severity of clinical presentation in patients hospitalized with decompensated heart failure (HF). METHODS: This is a historical cohort study where data was collected from the medical records of patients admitted to a private hospital with decompensated heart failure between 2016 and 2023. RESULTS: The most common comorbidities included systemic arterial hypertension in 79 out of 96 patients (82.2%), previous HF in 46 (47.9%), dyslipidemia in 41 (42.7%), and diabetes mellitus in 38 (39.5%). The data revealed that patients who died of cardiac causes during hospitalization had higher NP values compared to those who did not experience the same outcome. Among these deaths, 57.14% of patients exhibited hemodynamic instability on hospital admission (p=0.017). Additionally, two patients were readmitted within 6 months of discharge due to a new episode of decompensated HF, both presenting hemodynamic instability on admission (p=0.03), and eventually progressed to cardiac death. Cardiac and non-cardiac deaths were associated with higher NT-proBNP values (p=0.043). CONCLUSION: The findings indicate that higher NP levels in patients hospitalized with decompensated HF correlate with greater initial severity and long-term, including an increased likelihood of hemodynamic instability and a higher risk of readmission, respectively. Elevated NT-proBNP values are also linked to a higher mortality rate.

Combining Loop and Thiazide Diuretics Across the Left Ventricular Ejection Fraction Spectrum: The CLOROTIC Trial

BackgroundThe addition of hydrochlorothiazide (HCTZ) to furosemide in the CLOROTIC (Combining Loop with Thiazide Diuretics for Decompensated Heart Failure) trial improved the diuretic response in patients with acute heart failure (AHF). ObjectivesThis work aimed to evaluate if these results differ across the spectrum of left ventricular ejection fraction (LVEF). MethodsThis post hoc analysis of the randomized, double-blind, placebo-controlled CLOROTIC trial enrolled 230 patients with AHF to receive either HCTZ or a placebo in addition to an intravenous furosemide regimen. The influence of LVEF on primary and secondary outcomes was evaluated. ResultsThe median LVEF was 55%: 166 (72%) patients had LVEF >40%, and 64 (28%) had LVEF ≤40%. Patients with a lower LVEF were younger, more likely to be male, had a higher prevalence of ischemic heart disease, and had higher natriuretic peptide levels. The addition of HCTZ to furosemide was associated with the greatest weight loss at 72 of 96 hours, better metrics of diuretic response, and greater 24-hour diuresis compared with placebo, with no significant differences according to the LVEF category (using 2 LVEF cutoff points: 40% and 50%) or LVEF as a continuous variable (all P values were insignificant). There were no significant differences observed with the addition of HCTZ in terms of mortality, rehospitalizations, or safety endpoints (impaired renal function, hyponatremia, and hypokalemia) among the 2 LVEF groups (all P values were insignificant). ConclusionsAdding HCTZ to intravenous furosemide seems to be effective strategy for improving diuretic response in AHF without treatment effect modification according to baseline LVEF. (Combining Loop with Thiazide Diuretics for Decompensated Heart Failure [CLOROTIC], NCT01647932; Randomized, double blinded, multicenter study, to asses Safety and Efficacy of the Combination of Loop With Thiazide-type Diuretics vs Loop diuretics with placebo in Patients With Decompensated, EudraCT Number 2013-001852-36)

Impact of malnutrition in patients with severe heart failure.

The role of malnutrition among patients with severe heart failure (HF) is not well established. We evaluated the incidence, predictors, and prognostic impact of malnutrition in patients with severe HF. Nutritional status was measured using the geriatric nutritional risk index (GNRI), based on body weight, height and serum albumin concentration, with malnutrition defined as GNRI ≤98. It was assessed in consecutive patients with severe HF, defined by at least one high-risk 'I NEED HELP' marker, enrolled at four Italian centres between January 2020 and November 2021. The primary endpoint was all-cause mortality. A total of 510 patients with data regarding nutritional status were included in the study (mean age 74 ± 12 years, 66.5% male). Among them, 179 (35.1%) had GNRI ≤98 (malnutrition). At multivariable logistic regression, lower body mass index (BMI) and higher levels of natriuretic peptides (B-type natriuretic peptide [BNP] > median value [685 pg/ml] or N-terminal proBNP > median value [5775 pg/ml]) were independently associated with a higher likelihood of malnutrition. Estimated rates of all-cause death at 1 year were 22.4% and 41.1% in patients without and with malnutrition, respectively (log-rank p < 0.001). The impact of malnutrition on all-cause mortality was confirmed after multivariable adjustment for relevant covariates (adjusted hazard ratio 2.03, 95% confidence interval 1.43-2.89, p < 0.001). In a contemporary, real-world, multicentre cohort of patients with severe HF, malnutrition (defined as GNRI ≤98) was common and independently associated with an increased risk of mortality. Lower BMI and higher natriuretic peptides were identified as predictors of malnutrition in these patients.

Effects of empagliflozin on collagen biomarkers in patients with heart failure: Findings from the EMPEROR trials.

Extracellular matrix remodelling is one of the key pathways involved in heart failure (HF) progression. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) may have a role in attenuating myocardial fibrosis. The impact of SGLT2i on blood markers of collagen turnover in humans is not fully elucidated. This study aimed to investigate the effect of empagliflozin on serum markers of collagen turnover in patients enrolled in the EMPEROR-Preserved and EMPEROR-Reduced trials. Overall, 1084 patients (545 in empagliflozin and 539 in placebo) were included in the analysis. Procollagen type I carboxy-terminal propeptide (PICP), a fragment of N-terminal type III collagen (PRO-C3), procollagen type I amino-terminal peptide (PINP), a fragment of C-terminal type VIa3 collagen (PRO-C6), a fragment of type I collagen (C1M), and a fragment of type III collagen (C3M) were measured in serum at baseline, 12 and 52 weeks. A mixed model repeated measurements model was used to evaluate the effect of empagliflozin versus placebo on the analysed biomarkers. Higher baseline PICP, PRO-C6 and PINP levels were associated with older age, a more severe HF presentation, higher levels of natriuretic peptides and high-sensitivity troponin T, and the presence of comorbid conditions such as chronic kidney disease and atrial fibrillation. Higher PICP levels were associated with the occurrence of the study primary endpoint (a composite of HF hospitalization or cardiovascular death), and PRO-C6 and PINP were associated with the occurrence of sustained worsening of kidney function. On the other hand, PRO-C3, C1M, and C3M were not associated with worse HF severity or study outcomes. Compared to placebo, empagliflozin reduced PICP at week 12 by 5% and at week 52 by 8% (week 12: geometric mean ratio = 0.95, 95% confidence interval [CI] 0.91-0.99, p = 0.012; week 52: geometric mean ratio = 0.92, 95% CI 0.88-0.97, p = 0.003). Additionally, empagliflozin reduced PRO-C3 at week 52 by 7% (week 12: geometric mean ratio = 0.98, 95% CI 0.95-1.02, p = 0.42; week 52: geometric mean ratio = 0.93, 95% CI 0.89-0.98, p = 0.003), without impact on other collagen markers. Our observations are consistent with experimental observations that empagliflozin down-regulates profibrotic signalling. The importance of such an effect for the clinical benefits of SGLT2i in HF remains to be elucidated.

A Phenomapping Tool and Clinical Score to Identify Low Diuretic Efficiency in Acute Decompensated Heart Failure

BackgroundIndividuals with acute decompensated heart failure (ADHF) have a varying response to diuretic therapy. Strategies for the early identification of low diuretic efficiency to inform decongestion therapies are lacking. ObjectivesThe authors sought to develop and externally validate a machine learning–based phenomapping approach and integer-based diuresis score to identify patients with low diuretic efficiency. MethodsParticipants with ADHF from ROSE-AHF, CARRESS-HF, and ATHENA-HF were pooled in the derivation cohort (n = 794). Multivariable finite-mixture model-based phenomapping was performed to identify phenogroups based on diuretic efficiency (urine output over the first 72 hours per total intravenous furosemide equivalent loop diuretic dose). Phenogroups were externally validated in other pooled ADHF trials (DOSE/ESCAPE). An integer-based diuresis score (BAN-ADHF score: blood urea nitrogen, creatinine, natriuretic peptide levels, atrial fibrillation, diastolic blood pressure, hypertension and home diuretic, and heart failure hospitalization) was developed and validated based on predictors of the diuretic efficiency phenogroups to estimate the probability of low diuretic efficiency using the pooled ADHF trials described earlier. The associations of the BAN-ADHF score with markers and symptoms of congestion, length of stay, in-hospital mortality, and global well-being were assessed using adjusted regression models. ResultsClustering identified 3 phenogroups based on diuretic efficiency: phenogroup 1 (n = 370; 47%) had lower diuretic efficiency (median: 13.1 mL/mg; Q1-Q3: 7.7-19.4 mL/mg) than phenogroups 2 (n = 290; 37%) and 3 (n = 134; 17%) (median: 17.8 mL/mg; Q1-Q3: 10.8-26.1 mL/mg and median: 35.3 mL/mg; Q1-Q3: 17.5-49.0 mL/mg, respectively) (P < 0.001). The median urine output difference in response to 80 mg intravenous twice-daily furosemide between the lowest and highest diuretic efficiency group (phenogroup 1 vs 3) was 3,520 mL/d. The BAN-ADHF score demonstrated good model performance for predicting the lowest diuretic efficiency phenogroup membership (C-index: 0.92 in DOSE/ESCAPE validation cohort) that was superior to measures of kidney function (creatinine or blood urea nitrogen), natriuretic peptide levels, or home diuretic dose (DeLong P < 0.001 for all). Net urine output in response to 80 mg intravenous twice-daily furosemide among patients with a low vs high (5 vs 20) BAN-ADHF score was 2,650 vs 660 mL per 24 hours, respectively. Participants with higher BAN-ADHF scores had significantly lower global well-being, higher natriuretic peptide levels on discharge, a longer in-hospital stay, and a higher risk of in-hospital mortality in both derivation and validation cohorts. ConclusionsThe authors developed and validated a phenomapping strategy and diuresis score for individuals with ADHF and differential response to diuretic therapy, which was associated with length of stay and mortality.

Echocardiography in inflammatory heart disease: A comparison of giant cell myocarditis, cardiac sarcoidosis, and acute non-fulminant myocarditis

Giant cell myocarditis (GCM) and cardiac sarcoidosis (CS) are, in contrast to acute non-fulminant myocarditis (ANFM), rare inflammatory diseases of the myocardium with poor prognosis. Although echocardiography is the first-line diagnostic tool in these patients, their echocardiographic appearance has so far not been systematically studied. We assessed a total of 71 patients with endomyocardial biopsy-proven GCM (n=21), and CS (n=25), as well as magnetic resonance-verified ANFM (n=25). All echocardiographic examinations, performed upon clinical presentation, were reanalysed according to current guidelines including a detailed assessment of right ventricular (RV) dysfunction. In comparison with ANFM, patients with either GCM or CS were older (mean age (±SD) 55±12 or 53±8 vs 25±8years), more often of female gender (52% or 24% vs 8%), had more severe clinical symptoms and higher natriuretic peptide levels. For both GCM and CS, echocardiography revealed more frequently signs of left ventricular (LV) dysfunction in form of a reduced ejection fraction (p<0.001), decreased cardiac index (p<0.001) and lower global longitudinal strain (p<0.001) in contrast to ANFM. The most prominent increase in LV end-diastolic volume index was observed in CS. In addition, RV dysfunction was more frequently found in both GCM and CS than in ANFM (p=0.042). Both GCM and CS have an echocardiographic and clinical appearance that is distinct from ANFM. However, the method cannot further differentiate between the two rare entities. Consequently, echocardiography can strengthen the initial clinical suspicion of a more severe form of myocarditis, thus warranting a more rigorous clinical work-up.

Natriuretic Peptide Levels and Stages of Left Ventricular Dysfunction in Heart Failure with Preserved Ejection Fraction.

In heart failure with preserved ejection fraction (HFpEF), natriuretic peptide (NP) levels are frequently lower. In several trials, the outcome differed between patients with low and high NP levels. This suggests that NP could be used to identify distinct stages of left ventricular (LV) remodeling and myocardial tissue composition. This study investigated cardiac remodeling/dysfunction and myocardial tissue characteristics assessed by echocardiography and cardiac magnetic resonance (CMR) in HFpEF patients in relation to NP levels. Clinical and echocardiographic data of 152 HFpEF patients were derived from outpatient visits. A total of 71 HFpEF patients underwent CMR-derived T1-mapping. Multivariable regression analyses were performed to examine the association of NT-proBNP categories (</> median) and NT-proBNP as continuous variable with echocardiography and CMR-derived T1-mapping. Mean age was 71 ± 9, 93% of patients were women and median NT-proBNP was 195 pg/mL, with 35% of patients below the diagnostic cut-off value (<125 pg/mL). Patients with high NT-proBNP had comparable LV systolic function and LV relaxation but significantly worse LV stiffness and left atrial function compared with patients with low NT-proBNP. Higher NT-proBNP was significantly associated with higher LV stiffness and extracellular volume fraction (ECV) (β = 1.82, 95% CI: 0.19;3.44, p = 0.029). Higher NT-proBNP levels identify HFpEF patients with worse LV stiffness because of more severe myocardial extracellular matrix remodeling, representing an advanced stage of HFpEF.

Abstract 14862: Development and Validation of a Phenomapping Tool to Identify Patients With Diuretic Resistance in Acute Decompensated Heart Failure: A Multi-Cohort Analysis

Introduction: Individuals presenting with acute decompensated heart failure (ADHF) have varying response to diuretic therapy and short- and long-term prognosis. Hypothesis: If machine learning can risk stratify patients with ADHF and identify subgroups at risk for diuretic resistance. Methods: Participants with ADHF from the ROSE-AHF and CARRESS-HF clinical trials were included (n=451) and clustered using multivariable finite-mixture models based on diuretic efficiency (fluid output over first 72 hours per total intravenous loop diuretic dose). Differences in diuretic efficiency, in-hospital length of stay, and in-hospital mortality were assessed using linear and logistic regression models. Phenogroups were externally validated in trial (DOSE/ESCAPE, ATHENA-HF) and real-world (GWTG-HF) cohorts. Results: Clustering identified 3 phenogroups. Participants in phenogroup 1 (n=271, 60%) had worse diuretic efficiency [median(IQR) = 11.6(6.6-17.9) mL/mg) compared with phenogroups 2 (n=145, 32%) and 3 (n=35, 8%) [median(IQR) = 16.3(11.2-23.9) and 20.2(12.3-49.9) mL/mg, respectively; p&lt;0.001]. An integer-based risk score to predict phenogroup 1 (lowest diuretic efficiency) was created: BAN-ADHF ( Fig. ). Net urine output was 2600 vs. 1090mL per 24 hours in patients with scores of 5 and 15, respectively ( Fig ). In the external validation cohorts, participants with scores ≥11 vs. &lt;11 had significantly lower global well-being, higher natriuretic peptide levels on discharge, longer length of stay, and higher risk of in-hospital mortality. Conclusions: We developed and validated a phenomapping strategy and risk score for individuals with ADHF and differential response to diuretic therapy, which was associated with length of stay and mortality.

Elevated Natriuretic Peptides in Patients With Severe or Critical COVID-19: A Meta-Analysis.

The worldwide COVID-19 pandemic caused by SARS-CoV-2 has resulted in an extraordinary increase in the number of patients who are severely critically ill. For many of these patients, cardiovascular risk factors are key contributors to the development of severe illness. Laboratory markers for cardiac damage and failure, such as natriuretic peptides, are reported to be elevated in patients with severe COVID-19. We conducted a systematic review and meta-analysis to compare natriuretic peptide levels in patients with severe COVID-19 vs those with nonsevere COVID-19. PubMed and medRxiv were searched through April 7, 2020. The outcome of interest was the difference in B-type natriuretic peptide (BNP) or N-terminal-proBNP levels in patients with severe vs nonsevere COVID-19. We identified 9 retrospective cohort studies that had a total of 1,575 patients with COVID-19 who had their natriuretic peptides measured and were classified by disease severity. All studies were conducted in China. Patients with severe COVID-19 had significantly higher BNP levels than patients with nonsevere COVID-19 (mean difference, 69.56 pg/mL; 95% CI, 1.77-137.35 pg/mL; P = .04, I2 = 83%). Similarly, patients with severe COVID-19 had significantly higher N-terminal-proBNP levels than patients with nonsevere COVID-19 (mean difference, 518.65 pg/mL; 95% CI, 152.40-884.90 pg/mL; P = .006, I2 = 86%). In this study, Chinese patients with severe COVID-19 had higher natriuretic peptide levels than those with nonsevere COVID-19. Studies from all countries affected by the virus will help to further delineate whether the cause is directly or indirectly of cardiac origin and whether preexisting heart failure has an influence on this disparity.

Dapagliflozin and New York Heart Association functional class in heart failure with mildly reduced or preserved ejection fraction: the DELIVER trial.

This pre-specified analysis of the DELIVER trial examined whether clinical benefits of dapagliflozin in heart failure (HF) with left ventricular ejection fraction (LVEF) >40% varied by baseline New York Heart Association (NYHA) class and examined the treatment effects on NYHA class over time. Treatment effects of dapagliflozin by baseline NYHA class II (n=4713) versus III/IV (n=1549) were examined on the primary endpoint (cardiovascular death or worsening HF event) and key secondary endpoints. Effects of dapagliflozin on change in NYHA class at 4, 16, and 32 weeks were also evaluated. Higher baseline NYHA class was associated with older age, female sex, greater comorbidity burden, lower LVEF, and higher natriuretic peptide levels. Participants with baseline NYHA class III/IV, as compared with II, were independently more likely to experience the primary endpoint (adjusted hazard ratio [HR] 1.16 [95% confidence interval, 1.02-1.33]) and all-cause death (adjusted HR 1.22 [1.06-1.40]). Dapagliflozin consistently reduced the risk of the primary endpoint compared with placebo, irrespective of baseline NYHA class (HR 0.81 [0.70-0.94] for NYHA class II vs. HR 0.80 [0.65-0.98] for NYHA class III/IV; pinteraction =0.921). Participants with NYHA class III/IV had greater improvement in Kansas City Cardiomyopathy Questionnaire total symptom scores between baseline and 32 weeks (+4.8 [2.5-7.1]) versus NYHA class II (+1.8 [0.7-2.9]; pinteraction =0.011). Dapagliflozin was associated with higher odds of any improvement in NYHA class (odds ratio [OR] 1.32 [1.16-1.51]), as well as improvement to NYHA class I (OR 1.43 [1.17-1.75]), versus placebo at 32 weeks, with benefits seen as early as 4 weeks. Among symptomatic patients with HF and LVEF >40%, treatment with dapagliflozin provided clinical benefit irrespective of baseline NYHA class and was associated with early and sustained improvements in NYHA class over time.

Plasma Levels of Proprotein Convertase Subtilisin/Kexin Type 9 Are Inversely Associated with N-Terminal Pro B-Type Natriuretic Peptide in Older Men and Women.

Background and Aims: Cardiac natriuretic peptides (NPs) exert several metabolic effects, including some on lipid metabolism. Higher NPs levels are likely to be associated with a favorable lipid profile. In in vitro studies, NPs have been found to modulate low-density lipoprotein receptor (LDLR) trafficking by preventing proprotein convertase subtilisin/kexin type 9 (PCSK9) overexpression. The aim of our study is to investigate a possible association between plasma levels of PCSK9 and N-terminal pro B-type natriuretic peptide (NT-proBNP) in vivo. Methods: We performed a cross-sectional study on 160 consecutive older male and female patients hospitalized for medical conditions. Patients taking lipid-lowering drugs and patients with an admission diagnosis of acute heart failure were excluded. Fasting blood samples were collected after clinical stabilization of the acute illness, the day before discharge. Results: The mean age was 87.8 ± 6.4 years with a female prevalence (62.5%). The median NT-proBNP was 2340 (814–5397) pg/mL. The mean plasma PCSK9 was 275.2 ± 113.2 ng/mL. We found an inverse correlation between plasma PCSK9 and NT-proBNP (r = −0.280; p = 0.001). This association was confirmed after taking into account NT-proBNP tertiles (plasma PCSK9 levels: 317.4 ± 123.6 ng/mL in the first tertile, 283.3 ± 101.8 ng/mL in the second tertile, 231.3 ± 99.0 ng/mL in the third tertile, p = 0.001) and even after an adjustment for confounding factors (beta = −0.361, p = 0.001 for ln(NT-proBNP); beta = −0.330, p = 0.001 for NT-proBNP tertiles). The strength of the correlation between plasma PCSK9 and NT-proBNP was likely greater in patients affected by type 2 diabetes mellitus (r = −0.483; p = 0.006) and in male patients (r = −0.431, p = 0.001). Conclusion: The inverse association found between PCSK9 and NT-proBNP plasma levels in our real-life clinical study supports the hypothesis that NPs may play a role in cholesterol metabolism, possibly through an inhibitory action on circulating PCSK9 concentrations, thus increasing the availability of LDLR.

Comparison of Hepatic Tissue Characterization between T1-Mapping and Non-Contrast Computed Tomography.

Background: Non-contrast computed tomography (CT) is frequently used to assess non-alcoholic/metabolic fatty liver disease (NAFLD/MAFLD), which is associated with cardiovascular risk. Although liver biopsy is considered the gold standard for diagnosis, standardized scores and non-contrast computed tomography (CT) are used instead. On standard cardiac T1-maps on cardiovascular imaging (CMR) exams for myocardial tissue characterization hepatic tissue is also visible. We hypothesized that there is a significant correlation between hepatic tissue T1-times on CMR and Hounsfield units (HU) on non-contrast CT. Methods: We retrospectively identified patients undergoing a non-contrast CT including the abdomen, a CMR including T1-mapping, and laboratory assessment within 30 days. Patients with storage diseases were excluded. Results: We identified 271 patients (62 ± 15 y/o, 49% female) undergoing non-contrast CT and CMR T1-mapping within 30 days. Mean hepatic HU values were 54 ± 11 on CT and native T1-times were 598 ± 102 ms on CMR and there was a weak, but significant, correlation between these parameters (r = −0.136, p = 0.025). On age and sex adjusted regression analysis, lower liver HU values indicated a dismal cardiometabolic risk profile, including higher HbA1C (p = 0.005) and higher body mass index (p < 0.001). In contrast, native hepatic T1-times yielded a more pronounced cardiac risk profile, including impaired systolic function (p = 0.045) and higher NT-proBNP values (N-Terminal Brain Natriuretic Peptide) (p = 0.004). Conclusions: Hepatic T1-times are easy to assess on standard T1-maps on CMR but only weakly correlated with hepatic HU values on CT and clinical NAFLD/MAFLD scores. Liver T1-times, however, are linked to impaired systolic function and higher natriuretic peptide levels. The prognostic value and clinical usefulness of hepatic T1-times in CMR cohorts warrants further research.

Combined Role of Troponin and Natriuretic Peptides Measurements in Patients With Covid-19 (from the Cardio-COVID-Italy Multicenter Study)

Data concerning the combined prognostic role of natriuretic peptide (NP) and troponin in patients with COVID-19 are lacking. The aim of the study is to evaluate the combined prognostic value of NPs and troponin in hospitalized COVID-19 patients. From March 1, 2020 to April 9, 2020, consecutive patients with COVID-19 and available data on cardiac biomarkers at admission were recruited. Patients admitted for acute coronary syndrome were excluded. Troponin levels were defined as elevated when greater than the 99th percentile of normal values. NPs were considered elevated if above the limit for ruling in acute heart failure (HF). A total of 341 patients were included in this study, mean age 68 ± 13 years, 72% were men. During a median follow-up period of 14 days, 81 patients (24%) died. In the Cox regression analysis, patients with elevated both NPs and troponin levels had higher risk of death compared with those with normal levels of both (hazard ratio 2.94; 95% confidence interval 1.31 to 6.64; p = 0.009), and this remained significant after adjustment for age, gender, oxygen saturation, HF history, and chronic kidney disease. Interestingly, NPs provided risk stratification also in patients with normal troponin values (hazard ratio 2.86; 95% confidence interval 1.21 to 6.72; p = 0.016 with high NPs levels). These data show the combined prognostic role of troponin and NPs in COVID-19 patients. NPs value may be helpful in identifying patients with a worse prognosis among those with normal troponin values. Further, NPs’ cut-point used for diagnosis of acute HF has a predictive role in patients with COVID-19.

Body Composition and Incident Heart Failure in Older Adults: Results From 2 Prospective Cohorts.

BackgroundAging is associated with central fat redistribution and skeletal muscle decline, yet the relationships of tissue compartments with heart failure (HF) remain incompletely characterized. We assessed the contribution of body composition to incident HF in elders.Methods and ResultsParticipants from 2 older cohorts who completed dual‐energy X‐ray absorptiometry (DEXA) and, in one cohort, computed tomography were included. We evaluated associations with incident HF for DEXA principal components (PCs) and total lean, appendicular lean, total fat and trunk fat mass; and for computed tomography measures of abdominal visceral and subcutaneous fat, thigh muscle, intermuscular fat area and thigh muscle density. DEXA analysis included 3621, and computed tomography analysis 2332 participants. During median follow‐up of 11.8 years, 927 participants developed HF. DEXA principal components showed no relationship with HF. After adjustment for height, weight, and cardiovascular risk factors, total lean mass was near significantly associated with higher HF (hazard ratio [HR], 1.25 per SD [1.00–1.56]), whereas total fat mass and thigh muscle density were significantly related to lower HF (HR, 0.82 [0.68–0.99] and HR, 0.87 [0.78–0.97], respectively). Patterns were similar for HF subtypes. The relationships with HF for total lean and fat mass were attenuated after adjusting for intercurrent atrial fibrillation or excluding high natriuretic peptide levels.ConclusionsTotal lean mass was positively associated, while total fat mass and thigh muscle density were inversely associated, with incident HF. These findings highlight the limitations of DEXA for assessment of HF risk in elders and support the preeminence of computed tomography–measured skeletal muscle quality over mass as a determinant of HF incidence.

Abstract 10147: Temporal Change and Its Determinants of Psychological Symptoms During Hospitalization in Patients with Heart Failure

Introduction: Patients with heart failure (HF) could suffer from psychological symptoms such as anxiety and depression. However, these symptoms are rarely evaluated in hospitalized patients with HF, and may be underrecognized in daily practice. Methods: We prospectively evaluated consecutive hospitalized patients with HF at our institution between October 2019 and January 2021 using Hospital Anxiety and Depression Scale (HADS) on admission and at discharge. The HADS consists of 7 questions each for anxiety (HADS-A) and depression (HADS-D), both of which are graded by 0-3. Total scores were categorized as follows; 0-7 indicating no symptoms, 8-10 indicating mild, and 11-21 indicating significant anxiety or depression. Worsening symptoms during hospitalization was defined as that category of HADS at discharge was poorer than that on admission. Results: Of 224 (mean age: 77.5±12.4 years, median N-terminal pro B-type natriuretic peptide: 4527 pg/mL and mean left ventricular ejection fraction: 44%), 35 (16%) and 62 (28%) had significant symptoms of anxiety and depression, respectively. During hospitalization, HADS-A significantly decreased, whereas HADS-D did not improve ( Figure ). Worsening anxiety and depression during hospitalization occurred in 19 (10%) and 40 (21%), respectively. In multivariable logistic regression analysis, advanced age (odds ratio [OR]: 1.41, 95% confidence interval [CI]: 1.02-1.94; P=0.02), higher natriuretic peptide level (OR: 1.89, 95% CI: 1.23-2.90; P&lt;0.01) and acute on chronic HF (OR: 3.70, 95% CI: 1.25-11.00; P=0.01) were associated with worsening anxiety, and longer hospitalization length (OR: 2.17, 95% CI: 1.08-4.35; P=0.03) was associated with worsening depression. Conclusions: Anxiety and depression were common and depression persisted during hospitalization for HF. We found several risk factors for worsening these symptoms, providing the optimal candidate for psychological care in hospitalized patients with HF.

Severe tricuspid regurgitation worsens prognosis outcome after edge-to-edge mitral valve repair

Abstract Introduction MitraClip has been well established for treatment of severe mitral regurgitation (MR). MR and tricuspid regurgitation (TR) often occur simultaneously and symptoms of biventricular heart failure can overlap. While it has been shown that TR grade regression can be achieved through repair of MR1, presence of moderate to severe TR can increase all-cause mortality after MitraClip2. There is currently no consensus on the management of combined MR and TR. We evaluated the impact of TR on echocardiographic and functional outcome after MitraClip. Methods 370 patients underwent MitraClip for moderate to severe MR at our center from 2010 to 2018. Patients were dichotomized into low grade TR (grade &amp;lt;I - I (trace - mild)) and high grade TR (grade III - V (severe - torrential)). Moderate TR (grade II) was excluded. After MitraClip for MR, patients were followed up for 12 months and their echocardiographic and functional outcome was evaluated. Use of diuretic drugs throughout 12 month follow-up was registered. Results Low grade TR (&amp;lt;I - I) occurred in 225 patients (67.0%), high grade TR (III - V) was present in 111 patients (33.0%). 34 patients (9.2%) with moderate TR (II) were excluded. Patients with high grade TR had an increased morbidity (higher age, worse renal function, higher prevalence of atrial fibrillation, higher levels of natriuretic peptides, increased left atrial and right heart diameters, higher TR gradient). These patients also received significantly higher doses of torasemid (33.5±36.7 mg vs. 21.6±20.9 mg, p=0.003) and furosemid (163.4±155.5 mg vs. 75.8±72.3 mg, p=0.01). Average grade of MR at baseline was similar in both groups (2.9±0.46 vs. 2.8±0.5, p=0.66). Procedural success of MR repair was achieved similarly in both groups (96.4% vs. 96.9%, p=0.82) and residual MR grade immediately after device implantation was comparable (p=0.61). However, recurrent MR in the high grade TR group increased during follow up, while MR further decreased in the low grade TR group (3 months: 1.24±0.7 vs. 1.16±0.7, p=0.5; 12 months: 1.46±0.93 vs. 1.12±0.61, p=0.04). Accordingly, use of diuretic drugs after 12 months rose in the high grade TR group while it did not change or even decreased in the low grade TR group (torasemid: 40.2±48.4 mg vs. 24.1±30.0 mg, p=0.04; furosemid: 197.5±251.0 mg vs. 67.1±81.8 mg, p=0.22). Kaplan-Meier-Analysis showed significantly higher mortality (24.9 vs. 14.1%, p=0.01), higher risk for heart failure induced rehospitalisation (25,4 vs. 12,5%, p=0.005) and for major adverse cardiac and cerebrovascular events (MACCE: 42.3 vs. 29.1%, p=0.008) in the high grade TR group after 12 months. Conclusion MitraClip patients for MR with concomitant high grade TR (≥ III) had an increased morbidity at baseline compared to low grade TR patients. By MitraClip comparable reduction of MR was achieved. However, during 12 month follow-up in the high grade TR group recurrent MR occurred more often while use of diuretics increased. Funding Acknowledgement Type of funding sources: None.

Impact of cardiac rehabilitation on inflammation in patients with ischaemic cardiomyopathy

Abstract Introduction The benefits of cardiac rehabilitation (CR) in patients with ischaemic cardiomyopathy are well-known. However, inflammatory states have been associated to an increased risk of cardiovascular events. Purpose Evaluate the impact of CR in the serum levels of inflammatory biomarkers and identify potential predictors of that effect. Methods We retrospectively studied consecutive patients with ischaemic cardiomyopathy who completed a CR programme between 2011 and 2017. Patients underwent a supervised exercise training protocol, twice a week during a period of 8 to 12 weeks. Functional capacity was evaluated by metabolic equivalents assessed prior the beginning and 3 months after the programme with a symptom limited exercise treadmill test. Patients without levels of serum C-reactive protein at beginning and at the end of CR programme were excluded. Median variation of serum C-reactive protein was assessed and two groups were defined: one with levels above that and one with levels below. Results Of 250 patients (60.3±11.1 years, 84% male), 67% were admitted after an acute myocardial infarction. Left ventricular ejection fraction ≤40% before CR was present in 32% of individuals. Median levels of serum C-reactive protein before CR were 8.8 (3.1–21.7) mg/L and median variation after CRP was a decrease of 5.1 (0.9–17.7) mg/L (p&amp;lt;0.001). Before CR, higher levels of serum C-reactive protein were seen in obese (15.7 [8–52.7] versus 8.8 [3.2–27.8], p=0.04) and those with higher NT-proBNP (p&amp;lt;0.001). Patients with decrease of &amp;gt;5.1mg/L of serum C-reactive protein had lower prevalence of hypertension (18% versus 30%, p=0.02), higher prevalence of obesity (16% versus 7%, p=0.03), lower levels of HDL cholesterol (38.3 [11.1] versus 43.2 [12.6], p&amp;lt;0.001) and higher levels of NT-proBNP (1079 [610.3–1988] versus 488 [215–777], p&amp;lt;0.001) at baseline. An increase of at least of 10% of functional capacity after CR was reached in 65% of patients, similar between groups. Patients with decrease of serum C-reactive protein &amp;gt;5.1mg/L had also higher reduction of NT-proBNP after CR comparing to baseline (491.1 [142.7–948.5] versus 162.0 [30.9–295.2], p&amp;lt;0.001). Conclusions Serum levels of inflammatory biomarkers decreased after CR in patients with ischaemic cardiomyopathy. Normotension, obesity, lower HDL and higher levels of natriuretic peptides are associated to a better response. Funding Acknowledgement Type of funding sources: None.