Higher B-type Natriuretic Peptide Levels Research Articles

Prognostic role of high-sensitivity cardiac troponin T in patients with cardiac sarcoidosis: insights from ILLUMINATE-CS.

The prognostic role of high-sensitivity cardiac troponin T (hs-cTnT) as a biomarker in patients with cardiac sarcoidosis (CS) has yet to be fully determined, especially when compared with B-type natriuretic peptide (BNP). In this post-hoc analysis of the ILLUMINATE-CS (ILLUstration of the Management and prognosIs of JapaNese pATiEnts with Cardiac Sarcoidosis), which is a multicentre retrospective observational study, we analysed 103 patients (62.2±10.9years old, 31.1% male) diagnosed as CS and with available data for hs-cTnT measured at the time of diagnosis. The primary outcome was the combined outcomes of all-cause death, fatal ventricular arrhythmia events and heart failure hospitalization. During a median follow-up period of 2.6 (inter-quartile range, 1.6-5.7) years, 24 primary outcomes were observed. Patients with a high hs-cTnT level, defined as a level above the median value (>0.016ng/mL), were associated with a higher incidence of adverse events than those with a low hs-cTnT level (log-rank, P=0.017). In Cox regression analysis, a high log-transformed hs-cTnT level and a high log-transformed BNP level were significant risk factors for primary outcome [hazard ratio (HR), 4.368 (95% confidence interval, CI, 1.032-18.480), P=0.045. and HR, 3.127 (95% CI, 1.029-9.499), P=0.044, respectively]. Patients with both high hs-cTnT and high BNP (>140pg/mL: above the median value) levels had a 3.49 (95% CI, 1.23-9.88)-fold increased risk of the primary outcome compared with patients with both low hs-cTnT and low BNP levels. In patients with CS, a high hs-cTnT level is a useful predictor of adverse events, and combined measurement of hs-cTnT and BNP further improves the prognostic value.

Predictors and clinical impact of worsening left ventricular ejection fraction after mitral transcatheter edge-to-edge repair.

Little is known about the effects of left ventricular ejection fraction (LVEF) worsening after transcatheter edge-to-edge valve repair (TEER) for mitral regurgitation (MR). This study investigated the predictors and clinical impact of LVEF worsening after TEER for primary MR (PMR) and secondary MR (SMR). This study included 2,019 patients (493 with PMR and 1,526 with SMR) undergoing successful TEER (postprocedural MR grade ≤2+) in the OCEAN-Mitral registry. The patients were categorised into worsened LVEF (wEF), defined as a relative decrease of >12.9% in LVEF at discharge, and preserved LVEF (pEF). The serial changes in left ventricular (LV) function at 1 year were also evaluated. Following TEER, 657 (32%) patients demonstrated wEF. The pEF group demonstrated both decreased left ventricular end-diastolic volumes (LVEDV) and end-systolic volumes (LVESV), and the wEF group showed significantly increased LVESV at discharge. Higher LVEF, larger LVEDV, higher B-type natriuretic peptide levels, and moderate/severe aortic regurgitation predicted wEF. Compared with baseline, the wEF group still demonstrated lower LVEF (46% to 43%; p<0.001) but significantly increased stroke volume (48 mL to 53 mL; p=0.001) at 1 year. The incidence of death or heart failure hospitalisation was similar between the wEF and pEF groups (hazard ratio 1.14, 95% confidence interval: 0.72-1.80; p=0.84) and also in patients with PMR and SMR. LVEF worsening after TEER was not uncommon and was caused by the increased LVESV. LV volumes and some patient-specific factors predicted worsened LVEF which was not associated with long-term clinical outcomes. OCEAN-Mitral registry: UMIN-CTR ID: UMIN000023653.

Low levels of apolipoprotein M are associated with increased risk of ventricular arrhythmias

Abstract Background Ventricular arrhythmia (VA) is a frequent cause of sudden cardiac death (SCD). Treatment to prevent SCD includes device therapy with implantable cardioverter defibrillator (ICD). Although the electrophysiology underlying VA have been described, the molecular understanding of VA risk remains unclear. Purpose To identify proteins that are associated with higher and lower risk of VA. Methods SMASH 1 Study was a prospective observational study of 490 patients treated with ICD. The plasma proteome was analyzed with the Olink Explore 384 Cardiometabolic platform at study inclusion, and patients were followed for mean 3.1± 0.7 years. VA events were defined as adjudicated ventricular fibrillation or sustained ventricular tachycardia registered from ICD recordings and clinical events were recorded from electronic health records. Protein concentrations were quantified relatively as normalized protein expression on a log2-transformed concentrations where a large number represents higher protein level in the sample. Results The mean age was 66±12 years, 83% were male and 51% had a primary prevention ICD-indication. Episode(s) of VA occurred in 137 patients (28%) during follow-up. In total, 353 distinct proteins were successfully analyzed in all patients. Among these, high B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) levels were associated with a higher risk of VA, while Apolipoprotein M (APOM) was the only protein significantly associated with a lower risk of VA after multiple testing using Benjamini-Hochberg correction (Figure, Panel A). After adjusting for age, sex, body mass index, coronary artery disease, heart failure, renal function, left ventricular ejection fraction and antiarrhythmic medication, only low APOM levels remained significantly associated with VA: HR 0.51 (95%CI 0.32-0.79] per log unit increase, p=0.003. Patients in the lowest quartile of APOM had a particularly high risk of incident VA: HR 2.26 (95%CI 1.60-3.19), p=3.61x10-6, compared to quartile 2-4 (Figure, Panel B). High APOM levels were also associated with a lower risk of HF hospitalizations (HR 0.25 [95%CI 0.16-0.40], p&amp;lt;0.001) and all-cause mortality (HR 0.36 [95%CI 0.22-0.60], p&amp;lt;0.001), and these associations remained significant in adjusted models. Conclusions Low levels of APOM are associated with a greater risk of incident VA, independently of established risk factors. Low APOM also predicted risk of HF hospitalizations and mortality in our cohort, which suggest protective cardiovascular effects of APOM. Figure: Association of individual proteomic measures with risk of ventricular arrhythmias (VA).A:Volcano plots of the associations of individual plasma proteins with incident VA. The dotted line represents the significance level at false discovery rate &amp;lt;0.05 and the red dots are significant proteins after multiple testing using Benjamini-Hochberg correction.B: Risk of VA by quartile of Apolipoprotein M.

Impact of beta-blocker uptitration on patients after transcatheter edge-to-edge mitral valve repair for secondary mitral regurgitation: The OCEAN-mitral registry

BackgroundOptimal medical therapy for patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge mitral valve repair (M-TEER) remains unclear. This study aimed to investigate the association between beta-blocker uptitration and clinical outcomes after M-TEER. MethodsUsing data from the Japanese multicenter registry, we examined 1474 patients who underwent M-TEER for SMR between April 2018 and June 2021. Beta-blocker uptitration was defined as an increased dose of beta-blockers 1 month after M-TEER compared with that before M-TEER. The 2-year clinical outcomes were compared between patients with and without beta-blocker uptitration, utilizing multivariable Cox regression analyses and propensity score matching (PSM). ResultsOf the 1474 patients who underwent M-TEER, 272 (18.4 %) were receiving increasing doses of beta-blockers at the 1-month follow-up. These patients had lower left ventricular ejection fraction (LVEF) and higher B-type natriuretic peptide levels. Most patients in the beta-blocker uptitration group received less than the target dose of beta-blockers. Multivariable Cox regression analyses showed that beta-blocker uptitration was significantly associated with a lower risk of all-cause (adjusted hazard ratio [HR]: 0.55; 95 % confidence interval [CI]: 0.36–0.84; P = 0.006) and cardiovascular mortalities (adjusted HR: 0.45, 95 % CI: 0.26–0.79, P = 0.006). PSM analyses revealed consistent findings. Subgroup analyses revealed a significant interaction between beta-blocker uptitration and LVEF≤40 % (interaction P = 0.018). ConclusionsIn patients with SMR, beta-blocker uptitration after M-TEER was associated with better clinical outcomes, especially in the group with an LVEF≤40 %. Efforts to uptitrate guideline-directed medical therapy after M-TEER for SMR may be necessary, even if reaching the target dose proves challenging.

Relationship between initial B-type natriuretic peptide levels and detection of atrial fibrillation with an insertable cardiac monitor in cryptogenic stroke: CRYPTON-ICM registry.

High B-type natriuretic peptide (BNP) levels are associated with new atrial fibrillation (AF). This study investigated the distribution of AF detection rates according to BNP levels in patients with cryptogenic stroke (CS) using an insertable cardiac monitor (ICM). We enrolled consecutive patients with CS who underwent ICM implantation between October 2016 and September 2020 at eight stroke centers in Japan. Those with BNP levels were divided into three groups by tertiles. We evaluated the association of BNP levels with AF detection. Youden's index was calculated to identify the optimal cutoff for BNP. Of 417 patients, we analyzed 266 patients with BNP data. The tertile range of BNP level was 19.0 to 48.5 pg/mL. AF detection rate was 13.3%/year, 12.8%/year, and 53.7%/year in the low-BNP (≤19.0), mid-BNP (19.1-48.4), and high-BNP (≥48.5) groups, respectively (log-rank trend p < 0.01). Compared with low-BNP group, the adjusted hazard ratios for AF detection in mid-and high-BNP groups were 0.91 [95% confidence interval (CI) 0.46-1.78] and 2.17 (95% CI 1.14-4.13), respectively. Receiver operating characteristic curve analysis showed the optimal cutoff value was 43.4 pg/mL. The area under curve using BNP to predict AF detection was 0.69. The BNP level was associated with AF detection in patients with CS. This relationship changed around the BNP levels of 40-50 pg/mL.

Differential Expression of Circulating miRNAs and Carfilzomib-Related Cardiovascular Adverse Events in Patients with Multiple Myeloma.

This study investigates the association between circulating microRNA (miRNA) expression and cardiovascular adverse events (CVAE) in multiple myeloma (MM) patients treated with a carfilzomib (CFZ)-based regimen. A cohort of 60 MM patients from the Prospective Observation of Cardiac Safety with Proteasome Inhibitor (PROTECT) study was analyzed. Among these, 31 patients (51.6%) developed CVAE post-CFZ treatment. The Taqman OpenArray Human microRNA panels were used for miRNA profiling. We identified 13 differentially expressed miRNAs at baseline, with higher expressions of miR-125a-5p, miR-15a-5p, miR-18a-3p, and miR-152-3p and lower expression of miR-140-3p in patients who later developed CVAE compared to those free of CVAE, adjusting for age, gender, race, and higher B-type natriuretic peptide levels. We also identified three miRNAs, including miR-150-5p, that were differentially expressed in patients with and without CVAE post-treatment. Additionally, five miRNAs responded differently to CFZ treatment in CVAE vs. non-CVAE patients, including significantly elevated post-treatment expression of miR-140-3p and lower expressions of miR-598, miR-152, miR-21, and miR-323a in CVAE patients. Pathway enrichment analysis highlighted the involvement of these miRNAs in cardiovascular diseases and vascular processes. These findings suggest that specific miRNAs could serve as predictive biomarkers for CVAE and provide insights into the underlying mechanisms of CFZ-CVAE. Further investigation is warranted before these findings can be applied in clinical settings.

Paradoxical prognostic impact of severe aortic stenosis following trans-catheter aortic valve implantation

BackgroundAortic valve replacement is recommended for patients with “very severe” aortic stenosis (AS), irrespective of symptomatic manifestation. Nonetheless, the prognostic ramifications of “very severe” AS, as opposed to “severe” AS, subsequent to trans-catheter aortic valve implantation (TAVI) remain enigmatic. MethodsWe enrolled consecutive patients who received TAVI at our institute between May 2015 and April 2021. We scrutinized the impact of baseline “very severe” AS upon 3-year all-cause death or heart failure hospitalization following TAVI, in comparison to “severe” AS. ResultsA total of 239 patients (84.8 ± 5.4 years old, 58 men) were included. Baseline “very severe” AS was observed in 65 (27 %) patients, who exhibited more advanced hypertrophy and higher B-type natriuretic peptide levels compared to those with “severe” AS (p < 0.05 for both). Baseline “very severe” AS was paradoxically associated with higher freedom from the primary endpoint following TAVI compared to those with “severe” AS (p = 0.01). ConclusionsThe presence of baseline “very severe” AS was paradoxically associated with improved clinical outcomes subsequent to TAVI, in contrast to the cases of “severe” AS.

Intrahepatic Transcriptomics Differentiate Advanced Fibrosis and Clinical Outcomes in Adults With Fontan Circulation

BackgroundThe molecular mechanisms underlying Fontan-associated liver disease (FALD) remain largely unknown. ObjectivesThis study aimed to assess intrahepatic transcriptomic differences among patients with FALD according to the degree of liver fibrosis and clinical outcomes. MethodsThis retrospective cohort study included adults with the Fontan circulation. Baseline clinical, laboratory, imaging, and hemodynamic data as well as a composite clinical outcome (CCO) were extracted from medical records. Patients were classified into early or advanced fibrosis. RNA was isolated from formalin-fixed paraffin-embedded liver biopsy samples; RNA libraries were constructed with the use of an rRNA depletion method and sequenced on an Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were performed with the use of DESeq2 and Metascape. ResultsA total of 106 patients (48% male, median age 31 years [IQR: 11.3 years]) were included. Those with advanced fibrosis had higher B-type natriuretic peptide levels and Fontan, mean pulmonary artery, and capillary wedge pressures. The CCO was present in 23 patients (22%) and was not predicted by advanced liver fibrosis, right ventricular morphology, presence of aortopulmonary collaterals, or Fontan pressures on multivariable analysis. Samples with advanced fibrosis had 228 upregulated genes compared with early fibrosis. Samples with the CCO had 894 upregulated genes compared with those without the CCO. A total of 136 upregulated genes were identified in both comparisons and were enriched in cellular response to cytokine stimulus or oxidative stress, VEGFA-VEGFR2 signaling pathway, TGF-β signaling pathway, and vasculature development. ConclusionsPatients with FALD and advanced fibrosis or the CCO exhibited upregulated genes related to inflammation, congestion, and angiogenesis.

The significance of early-onset malignant arrhythmias in ST-elevation myocardial infarction patients treated with primary percutaneous coronary intervention and their relationship with biomarkers

Background/Aim. Patients who were treated with primary percutaneous coronary intervention (pPCI) and survived ventricular tachycardia (VT) and ventricular fibrillation (VF) in the first 48 hrs after ST-elevation myocardial infarction (STEMI) had, in most investigations, a similar long-term prognosis of the outcome, compared to those patients who did not have VT and VF during the first 48 hrs after STEMI. The aim of the study was to determine the association of myocardial infarction markers: creatine kinase-MB fraction (CK-MB), heart failure marker ? B-type natriuretic peptide (BNP), and systemic inflammation factor ? C-reactive protein (CRP) with early VT and VF onset, in relation to patient mortality during the first six months after STEMI. Methods. The retrospective study included 971 patients with STEMI treated with pPCI for ten years. VF and sustained VT (sVT) were detected outside of the hospital and during the first 48 hrs of hospitalization. Results. During the first 4 8 hrs from admission, 1 08 ( 11.1%) patients had life-threatening arrhythmias, of which 75 (69.4%) had VF, and 33 (30.6%) had sVT and were treated with direct current ? DC shock and intravenous amiodarone. Intrahospital mortality was significantly higher in patients with VF/sVT in the first 48 hrs compared to patients without VF/sVT (14.8% vs. 5.7%, p = 0.001). BNP level had higher accuracy in the prediction of six-month death than the maximum blood level of CRP in patients without VF/sVT after 48 hrs. However, in patients with early-onset malignant arrhythmias, BNP showed a lower level of accuracy in predicting the six-month mortality, a s did the CRP values, which had almost the same level of accuracy. Admission glycemia had a much lower predictive value in both groups of patients compared to BNP and C RP [ 0.705 ( 0.628? 0.781), p &lt; 0.001 and 0.662 (0.521?0.803), p = 0.046, respectively]. In either of the groups, maximum CK-MB levels were not significant in predicting the six-month all-cause mortality. Conclusion. Our study indicates that STEMI patients with early onset of VF and sVT, treated with pPCI, with a high BNP level, have a statistically significantly higher mortality rate compared to patients with a lower BNP level.

Abstract 12043: Neutrophil Extracellular Traps in Heart Tissue Drive Cardiac Dysfunction and Adverse Outcomes in Dilated Cardiomyopathy

Background: Neutrophil extracellular traps (NETs) have emerged as crucial contributors to cardiovascular diseases, but the significance of NETs in heart failure remains unclear. Aims: We aimed to clarify the relevance of NETs in myocardial tissue in heart failure. Methods and Results: We studied consecutive 62 patients with idiopathic dilated cardiomyopathy (DCM) who underwent endomyocardial biopsy. Using immunohistochemistry, NETs were identified in heart tissue by detecting the colocalization of citrullinated histone H3, neutrophil elastase, and DAPI. DCM patients had significantly higher numbers of NETs per tissue area and per neutrophil compared to control subjects without heart failure (n=11, Figure A ) (P &lt; 0.05 and P &lt; 0.05, respectively). When categorizing DCM patients based on the presence or absence of NETs, patients with NETs (n=32) had lower left ventricular ejection fraction and higher B-type natriuretic peptide levels than those without NETs (P &lt; 0.05 and P &lt; 0.05, respectively). Kaplan-Meier analysis revealed that NETs-positive DCM patients had lower event-free survival rates from the composite of cardiac events including cardiac deaths, decompensated heart failure, and left ventricular assist device implantation over a median 768-day follow-up ( Figure B ). In a multivariable Cox proportional hazard model, the presence of NETs independently associated with the risk of adverse cardiac events (hazard ratio, 5.96; P &lt; 0.05). Ex vivo analysis revealed that NETs-containing conditioned medium from wild-type neutrophils impaired mitochondrial oxygen consumption in mouse adult cardiomyocytes (P &lt; 0.05), while genetic ablation of peptidyl arginine deiminase 4, a molecule essential for NETs formation, abolished this effect. Conclusion: NETs in myocardial tissue contribute to cardiac dysfunction and adverse outcomes in DCM patients, potentially through mitochondrial dysfunction of cardiomyocytes.

Clinical characteristics and prognostic impact of immune checkpoint inhibitor-associated myocarditis in advanced non-small cell lung cancer.

Myocarditis is a rare immune-related adverse events (irAEs) with high mortality rates, with few reports on its clinical characteristics and prognostic impact. This study designed to explore the associations between cardiac parameters and outcomes of myocarditis in advanced non-small cell lung cancer (NSCLC) who treated with immune checkpoint inhibitor (ICI). Fourteen patients diagnosed with ICI-associated myocarditis by clinicians were admitted to the study analysis. By Cox univariate and multivariate survival analyses, potential risk factors for the development of severe myocarditis were identified. Survival analysis was also performed to explore the prognosis of patients with myocarditis. Among patients with myocarditis, higher B-type natriuretic peptide (BNP) levels (P= 0.04) and conduction block (P= 0.03) were associated with progression to severe myocarditis. In addition, high lactate dehydrogenase (LHD) levels (P= .04) and myocarditis onset within 2 months (P= 0.02) were prognostic factors of severe myocarditis. The median progression-free survival (PFS) time and median overall survival (OS) time for all patients were 5.9 months and 18.5 months, respectively. However, there were no statistical differences between mild and severe cohorts in terms of PFS and OS (PFS: 4.5 vs. 8.5 months, P= 0.17; OS: 21.3 vs. 18.5months, P= 0.36). And we found that the earlier occurrence of myocarditis, worse PFS prognosis (4.5 months vs. 10.5 months, P= 0.008), while no difference in OS (18.5 months vs. 21.3 months, P= 0.35). Compared to mild myocarditis, severe myocarditis presented with higher BNP levels and cardiac conduction abnormalities. In addition, patients with mild and early myocarditis tended to have better survival rates.

Role of NT-pro B-type Natriuretic Peptide in Anemic Patients Presenting with High-output Cardiac Failure

ABSTRACT Background: Anemia commonly contributes to cardiovascular alterations, including heart failure (HF). High-output cardiac failure is a less common form of HF, characterized by heart’s inability to provide sufficient blood for the body’s demand. However, anemia sometimes remains undetected because the superficial cardiac function does not precisely reflect the adverse impact of anemia. Plasma B-type natriuretic peptide (BNP) is comes into role in these cases. Material and Method: This cross sectional study was conducted between August 2020 to September 2022 on 40 severe anaemic cases with Hb &lt; 8g/dl according to WHO classification irrespective of etiology with clinical signs of heart failure, age group- above 14 years. Results: Out of total 40 patients, 24 were male and 16 were female. In our study, among the anemic females, 9 (56%) belonged to the age group of &lt;30 years of age. In our study, out of 40 patients, 14 patients presented with high BNP and 26 patients presented with BNP within normal limits. The mean BNP range in patients with high BNP level was 290.6. Conclusion: Understanding the mechanisms of association between anemia and NT-proBNP may improve our understanding of cardiac pathophysiology and help target potential therapies to prevent the development and progression of HF.

Impact of Baseline Heart Failure on Acute Pulmonary Embolism Risk Stratification and Clinical Outcomes

Among patients with acute pulmonary embolism (PE), abnormal cardiac biomarkers and elevated right ventricular to left ventricular (RV/LV) diameter ratio are associated with increased morbidity and mortality. However, subjects with baseline heart failure (HF) have abnormalities in cardiac chamber dimensions and biomarkers. We sought to describe risk stratification variables in a cohort with acute PE and categorized HF status as no HF, HF with reduced ejection fraction (HFrEF), or HF with preserved ejection fraction (HFpEF). In total, 182 subjects were identified for this study, of whom 142 were categorized as having no HF, 16 as having HFrEF, and 24 as having HFpEF. The median age was 65 years [interquartile range 51 to 75 years], and 43% were male. Subjects with HFrEF had significantly greater LV diameters and significantly lower RV/LV diameter ratio (no HF 0.94, HFrEF 0.65, HFpEF 0.89, p=0.002). Subjects with HFrEF also had significantly higher B-type natriuretic peptide levels (no HF 112 pg/mL, HFrEF 835 pg/mL, HFpEF 241 pg/mL, p <0.001) and higher 90-day mortality rates. Among subjects with acute PE, those with baseline HFrEF had significantly greater LV diameter and lower RV/LV diameter ratio than those of patients with HFpEF or no HF. In addition, subjects with HFrEF had significantly higher B-type natriuretic peptide levels and worse survival at 90days. In conclusion, these results indicate that PE risk stratification using current guidelines, especially reliance on RV/LV ratio, is inaccurate among subjects with baseline HFrEF.

Transient decrease in B-type natriuretic peptide level after liver transplantation does not ensure favorable post-transplant 30-day outcomes.

High B-type natriuretic peptide (BNP) levels within the first 3 postoperative days (postBNPPOD3) after liver transplantation (LT) are greatly predictive of the 30-day mortality. We evaluated clinical impact of transient decrease in postBNPPOD3 compared to pretransplant BNP (preBNP) level on mortality and major adverse cardiac event (MACE) within 30 days after LT. We retrospectively evaluated 3,811 LT patients who measured delta BNP (deltaBNP), defined by serial postBNPPOD3 minus preBNP. Thirty-day all-cause mortality and MACE were estimated in patients with deltaBNP < 0 (n = 594, 15.6%) and > 0 (n = 3,217, 84.4%), respectively. Kaplan-Meier survival and multivariable Cox regression analysis were used. Within 30 days, 100 (2.6%) of all patients died. Unexpectedly, 30-day mortality rate (6.1% [95% CI: 4.2-8.4%] vs. 2.0% [95% CI: 1.5-2.5%], P < 0.001) and MACE (24.2% [95% CI: 20.4-28.5%] vs. 15.3% [95% CI: 14.0-16.7%], P < 0.001) were higher in patients with deltaBNP < 0 compared to those with deltaBNP > 0, respectively. Patients with deltaBNP < 0 had higher preBNP level (median [interquartile range], 251 [118, 586] vs. 43 [21, 92] pg/ml, P < 0.001) and model for end-stage liver disease score (26 [14, 37] vs. 14 [9, 23], P < 0.001) and more transfused intraoperatively. DeltaBNP < 0 remained significant after adjustments for potential confounders in multivariable analysis of 30-day mortality and MACE. DeltaBNP < 0 within the first 3 postoperative days is mainly attributed to pre-LT severe liver and cardiac disease status, therefore, transient decrease in BNP level after LT does not ensure favorable post-LT 30-day outcomes.

Multimodality imaging methods and systemic biomarkers in classical low-flow low-gradient aortic stenosis: Key findings for risk stratification.

The aim of the present study is to assess multimodality imaging findings according to systemic biomarkers, high-sensitivity troponin I (hsTnI) and B-type natriuretic peptide (BNP) levels, in low-flow, low-gradient aortic stenosis (LFLG-AS). Elevated levels of BNP and hsTnI have been related with poor prognosis in patients with LFLG-AS. Prospective study with LFLG-AS patients that underwent hsTnI, BNP, coronary angiography, cardiac magnetic resonance (CMR) with T1 mapping, echocardiogram and dobutamine stress echocardiogram. Patients were divided into 3 groups according to BNP and hsTnI levels: Group 1 (n = 17) when BNP and hsTnI levels were below median [BNP < 1.98 fold upper reference limit (URL) and hsTnI < 1.8 fold URL]; Group 2 (n = 14) when BNP or hsTnI were higher than median; and Group 3 (n = 18) when both hsTnI and BNP were higher than median. 49 patients included in 3 groups. Clinical characteristics (including risk scores) were similar among groups. Group 3 patients had lower valvuloarterial impedance (P = 0.03) and lower left ventricular ejection fraction (P = 0.02) by echocardiogram. CMR identified a progressive increase of right and left ventricular chamber from Group 1 to Group 3, and worsening of left ventricular ejection fraction (EF) (40 [31-47] vs. 32 [29-41] vs. 26 [19-33]%; p < 0.01) and right ventricular EF (62 [53-69] vs. 51 [35-63] vs. 30 [24-46]%; p < 0.01). Besides, there was a marked increase in myocardial fibrosis assessed by extracellular volume fraction (ECV) (28.4 [24.8-30.7] vs. 28.2 [26.9-34.5] vs. 31.8 [28.9-35.5]%; p = 0.03) and indexed ECV (iECV) (28.7 [21.2-39.1] vs. 28.8 [25.4-39.9] vs. 44.2 [36.4-51.2] ml/m2, respectively; p < 0.01) from Group 1 to Group 3. Higher levels of BNP and hsTnI in LFLG-AS patients are associated with worse multi-modality evidence of cardiac remodeling and fibrosis.

The Prognostic Value of B-Type Natriuretic Peptide in Patients With Cardiac Sarcoidosis Without Heart Failure: Insights From ILLUMINATE-CS.

Background The prognostic role of BNP (B-type natriuretic peptide) in patients with cardiac sarcoidosis without evident heart failure is unknown. Methods and Results This is a post hoc analysis of ILLUMINATE-CS (Illustration of the Management and Prognosis of Japanese Patients With Cardiac Sarcoidosis), a multicenter, retrospective, and observational study that evaluated the clinical characteristics and prognosis of cardiac sarcoidosis. We analyzed patients with cardiac sarcoidosis without evident heart failure at the time of diagnosis. The association between baseline BNP levels and prognosis was investigated. The primary end point was the combined end point of all-cause death, heart failure hospitalization, and fatal ventricular arrhythmia. In total, 238 patients (61.0±11.1 years, 37% men) were analyzed, and 61 primary end points were observed during a median follow-up period of 3.0 (interquartile range, 1.7-5.8) years. Patients with high BNP (BNP above the median value of BNP) were older and had a lower renal function and left ventricular ejection fraction than those with low BNP values. Kaplan-Meier curve analysis indicated that high BNP levels were significantly associated with a high incidence of primary end points (log-rank P=0.004), and this association was retained even in multivariable Cox regression (hazard ratio, 2.06 [95% CI, 1.19-3.55]; P=0.010). Log-transformed BNP as a continuous variable was associated with the primary end point (hazard ratio, 2.12 [95% CI, 1.31-3.43]; P=0.002). Conclusions High baseline BNP level was an independent predictor of future adverse events in patients with cardiac sarcoidosis without heart failure at the time of diagnosis. Registration URL: https://www.umin.ac.jp/english/; Unique Identifier: UMIN-CTR: UMIN000034974.

Clinical Features of Heart Failure in Patients With Hypertrophic Cardiomyopathy in a Regional Japanese Cohort - Results From the Kochi RYOMA Study.

The clinical features of heart failure (HF) in patients with hypertrophic cardiomyopathy (HCM) in Japan have not been fully elucidated.Methods and Results: In 293 patients with HCM (median age at registration, 65 (57-72) years) in a prospective cardiomyopathy registration network in Kochi Prefecture (Kochi RYOMA study), HF events (HF death or hospitalization for HF) occurred in 35 patients (11.9%) (median age, 76 (69-80) years), including 11 HF deaths during a median follow-up of 6.1 years. The 5-year HF events rate was 9.6%. Atrial fibrillation, low percentage of fractional shortening, and high B-type natriuretic peptide level at registration were predictors of HF events. The combination of these 3 factors had a relatively high positive predictive value (55%) for HF events and none of them had a high negative predictive value (99%). There were 4 types of HF profile: left ventricular (LV) systolic dysfunction (40%), severe LV diastolic dysfunction (34%), LV outflow tract obstruction (LVOTO) (20%), and primary mitral regurgitation (MR) (6%). HF deaths occurred in patients with LV systolic dysfunction or LV diastolic dysfunction, but none of patients with LVOTO or primary MR due to additional invasive therapies. In a Japanese HCM cohort, HF was an important complication, requiring careful follow-up and appropriate treatment.

Reverse Remodeling and Non-Contrast T1 Hypointense Infarct Core in Patients With Reperfused Acute Myocardial Infarction.

Non-contrast T1 hypointense infarct cores (ICs) within infarcted myocardium detected using cardiac magnetic resonance imaging (CMR) T1 mapping may help assess the severity of left ventricular (LV) injury. However, because the relationship of ICs with chronic LV reverse remodeling (LVRR) is unknown, this study aimed to clarify it. We enrolled patients with reperfused AMI who underwent baseline CMR on day-7 post-primary percutaneous coronary intervention (n=109) and 12-month follow-up CMR (n=94). Correlations between ICs and chronic LVRR (end-systolic volume decrease ≥15% at 12-month follow-up from baseline CMR) were investigated. We detected 52 (47.7%) ICs on baseline CMR by non-contrast-T1 mapping. LVRR was found in 52.1% of patients with reperfused AMI at 12-month follow-up. Patients with ICs demonstrated higher peak creatine kinase levels, higher B-type natriuretic peptide levels at discharge, lower LV ejection fraction at discharge, and lower incidence of LVRR than those without ICs (26.5% vs. 73.3%, P<0.001) at follow-up. Multivariate logistic regression analysis showed that the presence of ICs was an independent and the strongest negative predictor for LVRR at 12-month follow-up (hazard ratio: 0.087, 95% confidence interval: 0.017-0.459, P=0.004). Peak creatine kinase levels, native T1 values at myocardial edema, and myocardial salvaged indices also correlated with ICs. ICs detected by non-contrast-T1 mapping with 3.0-T CMR were an independent negative predictor of LVRR in patients with reperfused AMI.

β-Blockers are associated with increased B-type natriuretic peptide levels differently in men and women in heart failure with preserved ejection fraction.

β-Blocker (BB) use is a mainstay for the treatment of heart failure (HF) with reduced ejection fraction (HFrEF), whereas its efficacy for heart failure with preserved ejection fraction (HFpEF) remains controversial. Women outnumber men in HFpEF, whereas men outnumber women in HFrEF. Plasma B-type natriuretic peptide (BNP) is established as a biomarker for HF. We examined whether BB use is associated with plasma BNP levels differently in men and women with HFpEF. The study subjects comprised 721 patients with HFpEF [left ventricular ejection fraction (LVEF) ≥ 50%] (184 men, mean age 78.2 ± 9.2 yr and 537 women, mean age 83.1 ± 8.8 yr), 179 on BB (66 men and 113 women) and 542 no BB (118 men and 424 women), 583 in sinus rhythm (SR) and 138 in atrial fibrillation (AF). A multivariable logistic regression test was used. Plasma BNP levels were higher (P = 0.0005), systolic blood pressure and LVEF lower (P = 0.0003, and P = 0.0059, respectively) on BBs than on no BBs in women, whereas in men, plasma BNP levels, systolic blood pressure, and LVEF were not altered significantly (P = 0.0849, P = 0.9129, and P = 0.4718, respectively) on BBs compared with no BBs in patients with SR. Multivariable logistic regression analysis revealed that BB use and women were a positive and a negative predictor for high BNP levels (P = 0.003 and P = 0.032, respectively) in SR but not in AF. BB use was associated with high-plasma BNP levels and lower LVEF in women but not in men with HFpEF and SR, suggesting that the pathogenesis and treatment of HFpEF may differ in men and women in SR.NEW & NOTEWORTHY Pathogenesis and treatment for heart failure with preserved ejection fraction (HFpEF) may differ in men and women in sinus rhythm (SR).

The effect of subclinical thyroid dysfunction on B- type natriuretic peptide level

Thyroid hormones (THs) have a significant effect on the cardiovascular system. THs increase myocardium stretch, leading to the release of B-type Natriuretic Peptide (BNP), which is considered a diagnostic biomarker of heart failure (HF). Thyroid dysfunctions (subclinical hypothyroidism; SCH and subclinical hyperthyroidism; SCHyper) stimulate several changes in the heart by causing either diastolic or systolic left ventricular dysfunctions leading to HF. This study aims to measure the changes of B- type NP levels in cases of subclinical hypo and hyperthyroidism. The present study aims to measure the changes in B-type Natriuretic Peptide (BNP) levels in subclinical hypo and hyperthyroidism (SCH and SCHyper). A theoretical study was also conducted using a docking program to find the effectiveness of some drugs in inhibiting or promoting B-type Natriuretic Peptide (BNP). A case study was conducted in a private clinic, Mosul- Iraq, from (April 1st – Sep 1) 2021, with 25 healthy participants with normal functioning thyroids as a control group (EU). A newly diagnosed 25 SCH and 17 SCHyper patients participated in this study, considering that none of them have thyroid dysfunctions taking medicine, hypertension, heart diseases, renal failure, and pregnant women. They all were checked for Thyroid Function Tests (TFTs), Free Triiodothyronine (FT3), Free Thyroxin (FT4) and Thyroid Stimulating Hormone (TSH). The plasma level of BNP was measured in all participants of the three groups. The results showed that the plasma level of BNP was higher in SCHyper patients (10.97 pg/ml) as compared to that of SCH patients (8.09 pg/ml) and EU subjects (8.27 pg/ml). Hereby, we could state that subclinical hyperthyroidism, SCHyper, triggers BNP release. Therefore, it should be kept in mind that any high BNP levels due to SCHyper should be considered a reliable diagnostic biomarker of heart failure (HF). Keywords. Thyroid hormone(TH), Subclinical hypothyroidism(SCH), Subclinical hyperthyroidism(SCHyper), Chronic heart disease(CHD), Heart failure(HF), B-type natriuretic peptide(BNP), Docking Study.