Brain Natriuretic Peptide Levels Research Articles

Empagliflozin protects the heart from atrial fibrillation in rats through inhibiting the NF-κB/HIF-1α regulatory axis and atrial remodeling

Atrial fibrillation (AF) is the most common form of sustained cardiac arrhythmia. The current study aimed to investigate the potential of empagliflozin (EMPA) to protect against acetylcholine (ACh)/calcium chloride (CaCl2)-induced AF in rats and elucidate the possible underlying mechanism of action. Rats were randomly assigned to five groups, as follows: CTRL group: received 1 ml/kg isotonic saline; AF group: received 1 ml/kg induction mixture of ACh/CaCl2 (60 µg ACh and 10 mg CaCl2 per ml); EMPA group: received 30 mg/kg EMPA; AF + EMPA10 group: received the induction mixture concurrent with 10 mg/kg EMPA; AF + EMPA30 group: received the induction mixture concurrent with 30 mg/kg EMPA. Our results showed that EMPA administration inhibited the AF-related electrocardiographic abnormalities and decreased the serum brain natriuretic peptide levels. EMPA treatment maintained the cardiac redox balance, as indicated by reduced levels of the lipid peroxidation biomarker malonaldehyde while enhancing the antioxidant glutathione levels. Moreover, EMPA markedly repressed ACh/CaCl2-induced C-reactive protein, tumor necrosis factor, and interleukin-6 production. Interestingly, EMPA administration strongly suppressed cardiac transforming growth factor beta1, collagen type I, and alpha-smooth muscle actin expression levels in the AF rats. These results were consistent with our histopathological findings, which revealed the ameliorative effect of EMPA on AF-induced inflammatory and fibrotic lesions. Mechanistically, EMPA dose-dependently downregulated nuclear factor-kappa B (NF-κB) and hypoxia-inducible factor (HIF)-1α expressions. Besides, it attenuated the pro-apoptotic active caspase-3 while augmenting the anti-apoptotic B-cell lymphoma 2 expressions. Furthermore, EMPA dose-dependently suppressed cardiac phosphatidylinositol 3-kinase (PI3K)/Akt signaling. In conclusion, this study demonstrates that EMPA intervention, within AF induction, protects against ACh/CaCl2-induced AF in rats, exerting powerful antioxidant, anti-inflammatory, anti-fibrotic, and anti-apoptotic effects. These effects are mainly mediated through the targeting of the NF-κB/HIF-1α regulatory axis in a dose-dependent manner.

The outcomes of electronic personal health records in patients with heart failure or coronary artery disease.

There are limited data on the efficacy of smartphone-based personal health records (PHRs) in patients with cardiovascular disease. This study aimed to examine the processes, outcomes and challenges associated with the implementation of integrated PHRs in patients with heart failure (HF) or coronary artery disease (CAD). This prospective single-group study evaluated the effects of a PHR system with the capability to capture electronic health records and vital signs in patients with HF or CAD. The outcomes measured were the 6-month changes in blood pressure (BP), body weight (BW), brain natriuretic peptide (BNP) levels, lipid profiles and haemoglobin (Hb) A1c levels. Between June 2021 and March 2022, we enrolled 111 patients (median age: 61years and 47% women) with CAD and/or HF. Over 6months, the PHR review count distribution was skewed: median 749 times (lowest 2, highest 5724)/180days, suggesting both low and excessive PHR users. After 3days, 23% of the patients discontinued inputting their vital signs and medication status. At 6months, compared with patients who discontinued, those who continued to input their vital signs (N=86) showed a significant decrease in their systolic BP and LDL-C levels but not in the diastolic BP, BW, BNP, HDL-C, triglyceride or HbA1c levels. The implementation of smartphone-based PHRs in daily practice is challenging for patients with HF or CAD. However, we observed positive indications of the benefits of PHR in these patients. UMIN000044369.

Validation of Left Ventricular Filling Pressure Evaluation by Order of Tricuspid and Mitral Valve Opening in Patients With Atrial Fibrillation.

Accurate assessment of left ventricular filling pressure in patients with atrial fibrillation or flutter (AF) remains difficult. A novel 2-dimensional scoring system, visually assessing time difference between mitral valve and tricuspid valve opening (VMT) score, based on temporal analysis of early diastolic valve opening, could be applied to these patients. We aimed to determine the usefulness of the VMT score in patients with AF. We analyzed 119 consecutive patients with AF who underwent cardiac catheterization as a derivation cohort. The diagnostic performance of the VMT score was further evaluated in an external data set containing 189 patients with AF. Elevated left ventricular filling pressure was defined as a mean pulmonary arterial wedge pressure ≥15 mm Hg. The time sequence of atrioventricular valve opening was visually assessed and scored (0, tricuspid valve first; 1, simultaneous; 2, mitral valve first). When the inferior vena cava was dilated, 1 point was added, and the VMT score was finally graded as 0 to 3. Conventional Doppler parameters to estimate left ventricular filling pressure were also measured. Pulmonary arterial wedge pressure was elevated with an increase in the VMT score (0: 10±3, 1: 13±5, 2: 22±7, 3: 27±6 mm Hg; P<0.001), resulting in a significant rise in pulmonary arterial wedge pressure from VMT score 1 to 2. VMT≥2 predicted elevated pulmonary arterial wedge pressure with an accuracy of 87%, and the diagnostic accuracy of the VMT score was significantly higher than that of conventional Doppler parameters (C index, 0.88 versus 0.54-0.68; P<0.001). In addition, VMT ≥2 showed an incremental predictive value over plasma brain natriuretic peptide levels (C index, 0.79-0.93; P<0.001). In the external validation cohort, VMT≥2 demonstrated acceptable accuracy of 72%. VMT scoring was a useful echocardiographic marker of elevated left ventricular filling pressure and had an incremental benefit over practical biomarkers in patients with AF.

Abstract 4138545: Mitral Valve Replacement is associated with favourable Functional and Clinical Outcome as compared with Restrictive Mitral Annuloplasty in Patients with Severe Ischemic Mitral Regurgitation. A prospective longitudinal analysis

Background: Restrictive mitral annuloplasty (RMA) and chordal-sparing mitral valve replacement (MVR) are common options for treatment of chronic severe ischemic mitral regurgitation. Research question: in patients with severe ischemic mitral regurgitation the most effective surgical approach remains controversial Aim: to test whether MVR provides superior clinical and functional outcomes compared with RMA. Methods: a prospective longitudinal analysis on 187 patients (age: 66 ± 9 year; EF:35 ± 8 %) undergoing MVR or RMA and CABG for severe ischemic mitral regurgitation. Six-minute walking test and echocardiography were performed at preoperative baseline, at 1 year and at a median FU of 5 year (interquartile range: 2.9). Brain natriuretic peptide levels were also obtained. Mitral regurgitation was defined through a comprehensive and integrative approach. Recurrent mitral regurgitation was defined as a vena contracta ≥ 3 mm at follow-up, in patients with no persistent regurgitation at discharge. The primary outcome was a 5-year composite of all-cause mortality and rehospitalization for heart failure. Survival analysis was performed with Kaplan-Meier method. Cox regression analysis was used to verify any independent predictor of composite end-point Results: Baseline preoperative data were similar between the two group. Mitral valve replacement was performed in 49% of patients (n=92) and RMA in 51 % (n=95). At 5 year patients referred to prostheses showed significant improvement in six-minute walking test as compared to RMA (MVR: 290 ± 70 meters vs MRA: 165± 56 meters) (p &gt; 0.01) ( Figure 1 ). The brain natriuretic peptide values did not differ between the two group at 1 year whereas were significantly lower in the MVR group at 5 years (MVR: 135 pg/ml; interquartile range:100 vs RMA: 486 pg/ml; interquartile range: 68 (p&lt;0.01) ( Figure 2 ). At 5 years freedom from all-cause death and rehospitalization for heart failure was higher in the MVR group as compared to RMA (84 ±8.9% vs 61 ±12%, p&lt;0.01) ( Figure 3 ). According to the Cox analysis recurrent mitral regurgitation was found to be a predictor of clinical outcome (HR:5.4, 95% CI:1.3-23.2, p= 0.023). Conclusions: In patients with severe ischemic mitral regurgitation referred for surgery, chordal- sparing MVR and CABG may improve functional capacity, clinical outcome and brain natriuretic peptide levels, compared with RMA and CABG. The impact of these findings remains to be defined by larger studies on longer term

Abstract 4121812: Longitudinal Trajectory-Based Classification of Heart Failure with preserved Ejection Fraction: A Machine Learning Approach

Background: Heart failure (HF) with preserved ejection fraction (HFpEF) is a complex syndrome characterized by heterogeneous pathophysiology and dynamic changes in cardiac structure and function. Current research predominantly focuses on left ventricular ejection fraction (LVEF) or left ventricular structures with predefined categories. This study hypothesized that applying unsupervised methodologies to longitudinal echocardiography will reveal distinct trajectory patterns in cardiac structure and function related to clinical outcomes in HFpEF patients. Methods: This retrospective cohort study, conducted at UC Davis Medical Center (2014 to 2022), consisted of adult patients with HFpEF. The inclusion criteria included ICD HF codes, a left ventricular ejection fraction (LVEF) ≥50%, and a Brain natriuretic peptide (BNP) ≥100 pg/ml or N-terminal-pro BNP (NT-proBNP) ≥225 pg/ml. Longitudinal data were analyzed using unsupervised machine learning, including UMAP for dimensionality reduction and Gaussian Mixture Models for clustering. Primary and secondary outcomes included all-cause mortality and changes in BNP levels, respectively. Results: The study included 1,626 patients. The cohort had a median age of 69 years, was 57.5% female, and 51.8% white. Three distinct echocardiographic trajectory patterns emerged (p&lt;.05) among the HFpEF cohort. Trajectory #1 (n=568) exhibited a high-stable pattern with the highest mortality rates, Trajectory #2 (n=512) showed a high-decreasing pattern with high mortality rates, and Trajectory #3 (n=546) had a low-increasing pattern with the lowest mortality rates. Trajectories varied significantly in baseline characteristics and longitudinal echocardiographic changes, with Trajectory #3 having a lower baseline left ventricular mass index (p&lt;.001) and a higher mean arterial pressure ( p =.001) compared to the other trajectories. Kaplan-Meier survival analysis indicated significant differences in survival among the trajectories ( p =.004). Conclusion: The study utilized unsupervised analysis of longitudinal echocardiographic data to identify three distinct HFpEF trajectories, each associated with unique clinical features and outcomes. These findings underscore the heterogeneity of HFpEF and highlight the potential trajectory-based patient stratification to improve targeted intervention strategies. Future validation in larger, multicenter cohorts is warranted to enhance HFpEF management and patient prognosis.

Abstract 4137396: Evolution of Tricuspid Regurgitation and Clinical Outcomes in Patients with Heart Failure with Preserved Ejection Fraction: Insights from the PURSUIT-HFpEF Registry

Background: Tricuspid regurgitation (TR) is prevalent in patients with heart failure with preserved ejection fraction (HFpEF). However, due to its high vulnerability to hemodynamic loads, the long-term observation may heighten its prognostic values. Purpose: To investigate the evolution of TR and its impact on clinical outcomes in patients with HFpEF. Methods: An analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 1238 patients hospitalized for acute heart failure (HF) (diagnosed by using Framingham criteria) met the inclusion criteria: an LVEF ≥50% and brain natriuretic peptide level ≥100 pg/ml. After excluding patients who died within 1 year, we included 761 patients (age 82 ± 9 years; men, 45%; atrial fibrillation, 37%) whose echocardiographic data at discharge and 1 year were available. Results: At discharge, 165 patients (21.7%) had moderate to severe TR, which increased to 185 patients (24.3%) at 1 year. Patients were categorized into 4 groups based on the TR evolution: no or mild TR that remained unchanged (n = 522 [69%]), no or mild TR that worsened to moderate to severe (n = 74 [9.7%]), moderate to severe TR that improved to no or mild (n = 54 [7.1%]), and moderate to severe TR that remained unchanged (n = 111 [15%]). During a subsequent follow-up of 33 months, patients with persistent moderate to severe TR had significantly higher mortality rates than the other groups (25.7% vs. 27.0% vs. 27.8% vs. 44.1%, log-rank p &lt; 0.001). Even after adjusting for age, sex, body mass index, left atrial diameter, and left ventricular filling pressure, persistent moderate to severe TR was independently associated with subsequent mortality (hazard ratio, 2.06, 95% confidence interval 1.42-2.99, p &lt; 0.001) Conclusions: During a one-year follow-up, changes in the TR severity were not rare in patients with HFpEF. Persistent moderate to severe TR alone was associated with subsequent mortality, highlighting the need to address persistent TR to improve the prognosis.

Abstract 4125729: Elevated Pre-Procedural Serum Natriuretic Peptide Levels Are Associated with All-Cause Mortality in Patients Undergoing Transcatheter Edge-to-Edge Mitral Valve Repair: A Systematic Review and Meta-Analysis

Background: Transcatheter edge-to-edge mitral valve repair (TEER) is an established procedure in patients with severe mitral regurgitation (MR) and elevated surgical risk on optimal medical therapy. However, there remains considerable mortality in this patient population. Some studies have shown that serum brain natriuretic peptide (BNP) and N-terminal pro b-type natriuretic peptide (NT-proBNP) predict all-cause mortality after TEER, whereas other studies have shown mortality to be independent of these markers. To address this gap in knowledge, we sought to examine the existing literature to determine whether there is an association between pre-procedural serum natriuretic peptides and mortality after TEER. Hypothesis: Among patients undergoing TEER, elevated pre-procedural BNP and NT-proBNP are associated with increased all-cause mortality. Methods: Databases including MEDLINE, Embase, and Cochrane Library were searched from inception through September 2023 for studies assessing pre-procedural serum natriuretic peptide levels and mortality among patients undergoing TEER. Pooled hazard ratios (HR) and standardized mean differences (SMD) were calculated using a random-effects model estimated by restricted maximum likelihood with the Hartung-Knapp modification. Results: A total of 30 studies comprising 10259 patients undergoing TEER met inclusion criteria. 25 studies measured NT-proBNP and 5 studies measured BNP. Elevated pre-procedural NT-proBNP (&gt;5000 or &gt;10000 pg/mL) was associated with increased all-cause mortality in both adjusted (HR = 2.94; 95% CI = 1.75 - 4.95; I2 = 46.8%) and unadjusted (HR = 5.16; 95% CI = 1.85 - 14.40; I2 = 0.0%) analyses (Figures 1 and 2). Pre-procedural BNP and NT-proBNP were also significantly lower among survivors at 12 months compared to non-survivors (SMD = 0.82; 95% CI = 0.37 - 1.27; I2 = 78.3%) (Figure 3). This association was demonstrated in patients with primary or secondary MR. Conclusions: Pre-procedural BNP and NT-proBNP levels are significant predictors of all-cause mortality in patients undergoing TEER for primary or secondary MR. This supports the inclusion of BNP or NT-proBNP in pre-procedural assessments to help inform patient discussions and guide post-procedural follow-up and monitoring.

Abstract 4127345: National Cohort Study on Hypertensive Disorders of Pregnancy Among Women with Congenital Heart Disease: Insights from Multiple Centers

Background: Hypertensive disorders of pregnancy (HDP) are among the primary reasons for maternal and perinatal deaths globally. Encompassing chronic hypertension, pregnancy induced hypertension (PIH), and preeclampsia, HDP are among the most frequent complications encountered during pregnancy. Considering the emerging congenital heart disease (CHD) population globally, research on HDP in pregnancies with CHD is urgently needed. Methods: Outcomes for 2220 pregnant women with CHD were evaluated retrospectively from 1993 to 2016 and prospectively from 2017 to 2019 from 7 tertiary hospitals. Maternal death, cardiac complications, obstetric and offspring complications of completed pregnancies and their demographics, cardiac characteristics, and comorbidities were collected. To identify the risk factors for HDP, univariate and multivariate analysis were performed through logistic regression. Results: Of 2220 completed pregnancies with CHD from 7 tertiary institutions, 77 women had PIH, and 76 women had preeclampsia. The main CHD diagnosis of patients with PIH was shunt lesion (including ASD, VSD, and PDA), left heart abnormality (including AS/AI, BAV, and COA), and single ventricle (SV). The main CHD diagnosis of patients with preeclampsia was shunt lesion (including ASD, VSD, and PDA), left heart abnormality (including AS/AI and MS/MI), and right heart abnormality (including TOF, PS/PAS/PI, DORV and DCRV). In parturients with PIH, the mortality and incidence of heart failure were 2.60% and 15.58%, respectively. In parturients with preeclampsia, the mortality and incidence of heart failure were 6.58% and 23.68%, respectively. Pregnancies with HDP had a significantly higher incidence of adverse maternal and offspring events than pregnancies without HDP. Independent risk factors for HDP included multiple gestation, use of medically assisted reproduction, having elevated brain natriuretic peptide (BNP) level, delayed first ANC visit, and absence of strict antenatal supervision. Conclusion: In summary, the presence of HDP in women with CHD significantly increased the risk of mortality and morbidity for both the mother and the child, particularly in cases involving preeclampsia.

Abstract 4118949: Factors Influencing Left Ventricular Function Recovery Following Left Ventricular Assist Device Implantation in Pediatric Dilated Cardiomyopathy: Insights from Single-Cell RNA Sequencing Analysis

Background and Objective: Heart transplantation is a recognized treatment for pediatric severe heart failure, but long-term issues necessitate alternative treatments. Some dilated cardiomyopathy (DCM) cases show left ventricular function recovery after LVAD implantation. This occurrence could lead to new treatments, but mechanisms are unclear. This study explores preoperative molecular factors interacting with LVAD's effects using single-cell transcriptomics on clinical samples. Methods: Twenty-five pediatric DCM patients underwent Berlin Heart EXCOR (BHE) implantation at our institution since 2013. Those with left ventricular ejection fraction (LVEF) improving by &gt;20% were in the Recovery group (R), others in Non-Recovery (NR). Single-cell RNA-sequence was performed on myocardial tissue from six patients (three per group). Differential gene expression and pathway analysis were conducted for each cell type. Findings were validated by comparing them with histological evaluation or clinical examination in all 25 cases. Results: R: 10 patients; NR: 15. R's weight was 6.3 kg, NR's 9.9 kg (p=0.049); LVEF: R 23%, NR 16.5% (p=0.61). In pseudobulk analysis of cardiomyocytes, upregulated genes in R included NPPB, MYL7, PCDH9. KEGG analysis indicated activation of Tight Junction and ECM receptor pathways in R. In fibroblasts, major extracellular matrix proteins were higher in R, GSL gene expression in NR. Plasma Brain Natriuretic Peptide (BNP) at BHE implantation was significantly higher in R; 2913 [1836-3990 (95% CI)] vs 1278 [667-1888] pg/ml (Image1,2). No differences in tissue fibrosis rates were found between the groups. Conclusion: Alterations in gene expression patterns in some cell clusters, including cardiomyocytes, may contribute to left ventricular function recovery post-BHE implantation in pediatric DCM patients. Plasma BNP levels correlated with gene expression alterations, suggesting both a potentially protective effect on cardiomyocytes and a useful marker of LV functional recovery. Further validation of these candidate genes may elucidate intracellular molecular mechanisms.

Abstract 4138793: Impact of diabetes mellitus on the severity and long-term outcomes of chronic thromboembolic pulmonary hypertension: a retrospective cohort study

Background: Previous studies have indicated that diabetes mellitus (DM) is linked to the severity and mortality of both pulmonary thromboembolism and pulmonary arterial hypertension. But the relationships between diabetes and chronic thromboembolic pulmonary hypertension (CTEPH) have not been discussed. This study aims to investigate the relationships of DM with disease severity and clinical worsening events in patients with CTEPH. Methods: We analysed data of patients with CTEPH from the National Center for Cardiovascular Diseases in China between January 1, 2013 and August 31, 2023. A 2-group propensity score matching was conducted to adjust for differences between CTEPH patients with and without DM, employing a 1:1 pairing algorithm. The association between DM and long-term adverse outcomes was appraised utilizing multivariable Cox regression models. Subgroup analyses, predicated on age, sex, World Health Organization functional class (WHO-FC) and body mass index, were carried out to evaluated interaction effects. Results: In total, 489 consecutive CTEPH patients were included in the study, with 25.97% diagnosed with DM. Subsequent matched analysis comprised 127 patients with DM and 127 without DM. CTEPH patients with DM exhibited inferior WHO-FC as well as cardiac index, elevated N-terminal pro–brain natriuretic peptide levels, pericardial effusion, tricuspid annular plane systolic excursion / systolic pulmonary arterial pressure ratio and pulmonary vascular resistance. After adjusting for confounding factors, DM remained independently associated with adverse outcomes in patients with CTEPH. In addition, further subgroup analyses disclosed a more robust association in patients without overweight or obesity. Conclusions: DM correlates with heightened severity of CTEPH and serves as an autonomous predictor of long-term prognosis in CTEPH. Moreover, this correlation is more pronounced in individuals devoid of overweight or obesity.

Persistently low tricuspid annular plane systolic excursion and its prognosis in Japanese hospitalized patients with heart failure with reduced ejection fraction.

In patients with heart failure (HF) with reduced left ventricular ejection fraction (HFrEF), low tricuspid annular plane systolic excursion (TAPSE) on echocardiography is associated with poor prognosis. The significance of TAPSE changes post-HF treatment among HFrEF patients remains unclear. We evaluated the factors associated with persistently low TAPSE and its prognostic impact in Japanese hospitalized patients with HFrEF. We prospectively examined 260 HFrEF patients from the prospective observational HIJ-HF III study of HF patients hospitalized at Tokyo Women's Medical University between 2015 and 2019. Persistently low TAPSE was defined as TAPSE < 17mm on both pre- and 1-year post-discharge echocardiography. The primary endpoint of the study was all-cause mortality or re-hospitalization due to HF. Prognosis and characteristics were compared between patients with and without persistently low TAPSE. Using characteristics and echocardiography data, factors associated with persistently low TAPSE were assessed using logistic regression analysis. We identified the prognostic impact of persistently low TAPSE in HFrEF patients using Cox proportional hazards models. Seventy-eight (30%) of the 260 patients had persistently low TAPSE. They had higher New York Heart Association functional class; lower baseline TAPSE and left ventricular ejection fraction; and fewer angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Significant factors associated with persistently low TAPSE included higher brain natriuretic peptide level at 1year after discharge, lower baseline levels of TAPSE and septal s'. Over a follow-up period of 32months (range 12-69months) after the 1-year echocardiography, the rate of the primary endpoint was significantly higher among patients with persistently low TAPSE than that among others (n = 31 (40%) vs. n = 39 (21%), respectively, log-rank p < 0.001). Cox multivariate analysis revealed that persistently low TAPSE was independently associated with adverse events (Hazard ratio, 1.975; 95% confidence interval 1.183-3.295; p = 0.009). Exactly 30% of hospitalized patients with HFrEF had low TAPSE both pre- and 1-year post-discharge. Persistently low TAPSE had independent predictive value of prognosis in these patients.

Ferric carboxymaltose reduces the burden of arrhythmic events in heart failure with reduced ejection fraction: the role of the non-invasive arrhythmic biomarkers

BackgroundTreating iron deficiency (ID) with ferric carboxymaltose (FCM) in patients with heart failure with reduced ejection fraction (HFrEF) enhances morbidity, quality of life (QoL), and exercise capacity. MethodsThis single center, prospective follow-up study aims to assess FCM's impact on arrhythmic events and non-invasive markers in HFrEF patients with cardiac implantable electronic devices (CIEDs) and ID. Symptomatic HFrEF patients with ID and CIEDs scheduled for IV FCM were followed for 12-months. Arrhythmic activity was evaluated from CIEDs and non-invasive markers from Holter recordings pre- and post-FCM. Ventricular tachycardia/ventricular fibrillation (VT/VF) episodes, non-sustained VT (nsVT), late potentials (LPs), Microvolt T-wave alternans (MTWA), heart rate variability, turbulence (HRT) QTc, and premature ventricular contractions (PVCs, number and Lown and Wolf classification) were assessed. Left ventricular EF (LVEF), global longitudinal strain (LV GLS), QoL (KCCQ, EQ-5D-5L), six-minute walking distance (6MWD), peak oxygen consumption, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels were also recorded. ResultsNinety-six patients in optimal medical treatment participated (median age 71.9 [12.3] years, 83% male). Post-FCM treatment, VT/VF (P=0.043) and nsVT (P<0.001) frequency decreased significantly. The Lown and Wolf classification improved (P=0.002) and predicted VT/VF episodes better than other markers (AUC 0.737, P=.001). MTWA, LPs and HRT improved statistically significantly post-FCM. Hospitalization rates and NT-proBNP levels decreased, while LVEF, LV GLS, 6MWD, QoL and peak VO2 improved statistically significantly (P<0.001). ConclusionsOur study provides real-world evidence that IV FCM led to statistically significant reduction in ventricular arrhythmic episodes, as well as an improvement in non-invasive arrhythmic markers.

Long-term outcomes after transcatheter aortic valve implantation: derivation and validation of the long-TAVI prediction model

Abstract Background Identification of high-risk individuals after transcatheter aortic valve implantation (TAVI) is essential to personalized care. Established risk models require a plethora of variables, fail to account for biomarker dynamics and imaging parameters, mostly focus on the short term, and offer limited predictive performance. Purpose We aimed to develop an easily applicable prediction model for long-term mortality or heart failure (HF) admission following TAVI. Methods Patients undergoing TAVI at a high-volume university centre in the United Kingdom (n = 990) were recruited into a prospective cohort study. Enrolled patients were divided into a development cohort (07/2007 – 12/2016) and a validation cohort (01/2017 – 11/2018) and followed for up to 15.1 (median 5.3, interquartile range [IQR] 2.8 – 7.4) years. Patient characteristics along with pre- and post-procedural imaging results and brain natriuretic peptide (BNP) levels before the procedure and at 3 months were recorded. A clinical risk score for long-term mortality and HF admission (i.e., Long-TAVI risk score) was derived using Cox regression and evaluated using time-dependent area under the receiver operating characteristics curve (AUC). Results Age at presentation was 79.8 (standard deviation [SD] 8.9) years, 961 (99.0%) patients had signs of heart failure, left ventricular ejection fraction was 52 (SD 11.2), and pre-TAVI BNP levels were 298.0 (interquartile range [IQR] 159.0 – 571.5) pg/mL. High BNP levels at presentation (higher vs. lower than 400 pg/mL: HR 1.50, 95% CI 1.17 – 1.92, P &amp;lt; 0.001) and dynamic changes in BNP with the first 3 months (low/high vs. low/low: 2.61, 95% CI 1.17 – 5.86, P = 0.020; high/high vs. low/low: 2.41, 95% CI 1.26 – 4.64, P = 0.008) were independent predictors mortality or HF admission. The simple 8-item Long-TAVI score accounts for periprocedural BNP dynamics and shows good discrimination (AUC 0.76, 95% CI 0.72 – 0.79) and calibration in the development cohort performing similarly well in the external validation cohort (AUC 0.70, 95% CI 0.63 – 0.77). Long-TAVI significantly outperformed the logistic EURO score (AUC 0.56, 95% CI 0.52 – 0.59, P &amp;lt; 0.001). Conclusion Both pre-TAVI BNP levels and periprocedural BNP trajectories are independently associated with long-term outcomes after TAVI. Accounting for clinical characteristics, imaging parameters, and circulating BNP levels, the newly developed Long-TAVI risk score achieves high performance and provides the first prediction model for long-term mortality or HF admission. Long-TAVI represents a novel tool for personalized risk assessment in patients undergoing TAVI.Correlation at baseline A) and FUP B)Score performance A) and risk groups B)

Residual congestion in acute decompensated heart failure: A novel approach through microvascular imaging of renal circulation

Abstract Background In patients admitted for acute decompensated heart failure (ADHF), residual congestion at discharge is associated with adverse clinical outcomes. Traditionally, the extent of congestion has been inferred from central venous pressure, but it has also been highlighted that this is insufficient for a comprehensive evaluation of residual congestion. On the other hand, renal congestion is an important finding of organ congestion, and Superb Microvascular Imaging (SMI), a technique that reveals minute flow details, is promising for assessing renal circulation. We hypothesized that in patients with ADHF, assessment of renal circulation using SMI may be superior to conventional methods in assessing residual congestion. Methods In this prospective study, we enrolled 45 consecutive patients admitted with ADHF. We performed comprehensive evaluations including blood tests, echocardiography, and renal ultrasonography using SMI. The vascular index (VI), as measured by SMI, was calculated as the percentage of blood flow signal area in the region of interest. Subsequently, we calculated the intra-renal perfusion index (IRPI), representing cyclic variation in VI, as (maximum VI - minimum VI) within one cardiac cycle, divided by the maximum VI (Figure). Brain Natriuretic Peptide (BNP) levels were utilized to evaluate the state of decongestion. Results At discharge, the mean IRPI was 0.61±0.04, while the median BNP levels were 204.9 pg/ml (interquartile range: 102.7, 428.2). Patients exhibiting elevated log BNP levels at discharge (&amp;gt;2.31, based on median value) displayed significantly higher IRPI values [0.61(0.49, 0.86) vs 0.53(0.35, 0.59), p=0.02] and were older (80.8±8.5 vs 70.3±14.9 years, p=0.010). However, no significant differences were observed regarding laboratory parameters including hematocrit and creatinine levels, as well as echocardiographic parameters such as ejection fraction, E/e' ratio, and estimated right atrial pressure (RAP). Moreover, at discharge, creatinine levels (p=0.56) and estimated RAP (p=0.06) exhibited no significant correlation with IRPI. Conclusion Renal circulation evaluated by SMI may serve as a useful indicator of the extent of residual congestion at discharge compared to blood tests and echocardiographic estimates of right atrial pressure in patients admitted for ADHF.

Identifying heart failure dynamics using multi-point electrocardiograms and deep learning

Abstract Background Heart failure (HF) hospitalizations are related to poor survival outcomes, emphasizing the need for early detection and intervention. Recent studies have reported the potential of deep learning algorithms in identifying heart failure through electrocardiogram (ECG) with notable accuracy. However, evidence supporting their utility in the ongoing monitoring and follow-up of HF patients remains uncertain. Advanced diagnostic tools that can effectively track heart failure progression or improvement over time are needed. Purpose To address this challenge, we developed a deep learning model analyzing 12-lead ECG waveforms at two time points, aiming to detect HF deterioration or improvement, potentially revolutionizing HF management. Methods This study analyzed 32,045 ECGs from 6,892 unique adult patients (aged 18 years and older) visiting the Department of Cardiology at Kobe University Hospital. The participants were randomly assigned to training (4,284 patients), validation (1,034 patients), and test (1,034 patients) datasets. ElecTransformer was developed to classify HF status into deteriorated, improved, and no change classes based on ECG waveform signals at two different time points and to estimate brain natriuretic peptide (BNP) levels. Performance metrics, such as the area under the receiver operating characteristic curve (AUROC) and accuracy, were calculated, and attention mapping via gradient-weighted class activation mapping was utilized to interpret the model's decision-making ability. Results The patients had an average age of 65 years (±15.4 years) and BNP levels averaged 71.5 pg/mL (25.8 to 185.2 pg/mL). For HF status classification, ElecTransformer achieved an AUROC of 0.845 and an accuracy of 0.821, improving to an AUROC of 0.885 and an accuracy of 0.833 with baseline BNP integration. The ElecTransformer accurately estimated BNP levels from ECG data, evidenced by a correlation coefficient of 0.798. Averaged attention mapping showed that the QRS complex was the most important feature for determining model outputs with lesser effects seen for P waves and T waves variance Conclusions Harnessing a Transformer-based deep learning model to analyze multiple ECGs markedly improves the accuracy in detecting changes in heart failure status. This method offers a valuable non-invasive option for monitoring heart failure progression, potentially leading to better patient management and earlier intervention in heart failure treatment.Architecture and Performance of ModelsAveraged attention mapping

Basal inferior-septal segment is highly susceptible to deformation in the clinical spectrum of transthyretin-derived cardiomyopathy

Abstract Background The prevalence of transthyretin-derived cardiomyopathy (ATTR-CM) is increasing; however, understanding the morphological and functional manifestations within the left ventricle (LV) across the spectrum of heart failure (HF) remain limited. Purpose This study aims to assess the longitudinal strain (LS) using 2D speckle-tracking echocardiography in ATTR-CM patients and compared them with the features of magnetic resonance imaging (MRI). Methods 2D speckle-tracking echocardiography evaluated LS in 63 histology-confirmed ATTR-CM patients (median age: 78 years; male: 94%), with and without developing HF. Additionally, native T1 and extracellular volume (ECV) measured using MRI were compared with LS in 18-segments depicted on a Bull’s eye plot. Results Patients were grouped based on HF status: Group 1 (no HF symptoms, n=10), Group 2 (HF with preserved LV ejection fraction (LVEF), n=17), and Group 3 (reduced LVEF, n=36). Group 3 exhibited higher levels of brain natriuretic peptide and troponin T, and lower estimated glomerular filtration rate, compared with Group 1 and 2. Echocardiography revealed heightened LV thickness and decreased LVEF in Group 3. LS analysis revealed susceptibility to deformation in the basal inferior-septal segment, persisting even in Group 1. MRI revealed a high average native T1 level with minimal standard deviation (indicative of tissue homogeneity). However, this level increased as distance from the inferior-septal segment grew in the basal and mid-ventricular slices. Contrast images displayed maximal ECV in the basal and mid-ventricular inferior-septum, a phenomenon persisting in Group 1. Segmental LS decline, as assessed by echocardiography, correlated with ECV expansion but not with native T1 values. Conclusion 2D speckle-tracking echocardiography can identify segmental LS impairment in ATTR-CM patients, potentially reflecting amyloid burden and fibrosis extent. Our data suggest that amyloid deposition might be widespread from the basal inferior-septal segment to other areas.

The predisposing factors to heart failure diagnosis and early mortality among young adults in Africa: a narrative review

Abstract Introduction Heart failure (HF) is a major health concern mainly diagnosed among elderly individuals. Primarily, researchers have focused on this age group, nevertheless, compared to individuals from other regions of the world, Africans presents with HF two decades sooner (52 versus 79 years). Even though it manifests early, young persons (18–35 years old) are also diagnosed with HF with prognoses comparable to the older group. Less is known about how much study is concentrated on this age range, although globally, young adults of African origin make up the majority of those with an early onset of heart failure. Additionally, obtaining information about how HF impacts African youth remains challenging. Purpose To determine the cause of Africans' early HF diagnosis as well as the risk factors for HF diagnosis and early mortality among young adults. Methodology Three electronic databases— MEDLINE Ovid, Scopus, and CINAHL Plus—were searched using the Boolean operators. The first retrieved hits were checked for relevancy by titles and abstracts. Then, publications were fully screened for inclusion in the review based on the pre-established criteria. Also, reference lists of the articles were snowballed for pertinent studies. The scientific integrity of the studies was evaluated using a guided, in-depth peer-reviewed article on how to critically analyse clinical research and the Critical Appraisal Skill Programme (CASP) tool cohort checklist. Pertinent information regarding the study was analysed using a narrative review methodology. Eleven (11) articles out of the 135 pulled from the databases met the requirements for inclusion in the review after a thorough screening. One article was eliminated upon critical evaluation of the research's methodology, and an eligible article was discovered from snowballing reference lists. Therefore, only 11 articles qualified for this review study. Results Findings from the review show that HF is diagnosed earlier among Africans due to the early presentation of the major causes of HF before the age of 30 years. Rheumatic heart disease, cardiomyopathy, ischemic heart disease, HTN, and pulmonary illnesses (COPD, TB, and pulmonary arterial hypertension) are known aetiologies. More so, young adults who are diabetic, obese, have hyperlipidaemia or smoke cigarettes are more likely to develop HF. Furthermore, socioeconomic status, alcohol use, smoking, renal dysfunction, higher serum levels of brain natriuretic peptide (BNP) and creatine kinase (Isomer MB), cardiogenic shock, and decreased ejection fraction were the predictors of death with significant p-values (0.05). Conclusion Although HF affects young African adults disproportionately causing them to live lower quality of life and shorter lives, no research before this has been conducted. Therefore, further study is required to understand how HF affects this target age range (18 to 35 years) and to develop a long-term plan to fight this illness before it worsens.

Association of renal circulation at acute phase with decongestion level at discharge in patients admitted for acute decompensated heart failure

Abstract Background In patients admitted with acute decompensated heart failure (ADHF), renal hemodynamics may play an important role in the clinical course during hospitalization based on the close cardio-renal relationship. Superb Microvascular Imaging (SMI), distinguished by its advanced clutter suppression capabilities to reveal microflow details, holds promise for evaluating renal circulation. Consequently, our study aims to explore the association between renal circulation as assessed by SMI and the levels of brain natriuretic peptide (BNP) at discharge as an indicator of decongestion status. Methods In a prospective design, 45 ADHF patients were sequentially examined via renal ultrasound with SMI at discharge. The vascular index (VI) by SMI was calculated as the percentage of blood flow signal area in the region of interest. Then, the intra-renal perfusion index (IRPI) as an index of cyclic variation in VI, was calculated as the maximum VI minus the minimum VI within one cardiac cycle in the ROI divided by the Max.VI (Figure A). Results The values of IRPI were as follows: at 12h, 0.70±0.04; at 48h, 0.58±0.05; at 1W, 0.50±0.04; and at discharge, 0.61±0.04. The IRPI measured at 48h showed a stronger correlation with BNP at discharge (r = 0.57, p&amp;lt;0.001) than those at the other three points (Figure B). Patients with higher log BNP at discharge (&amp;gt; 2.31: determined by the median value) had significantly higher IRPI and age, and lower hemoglobin levels at 48h, however, there were no significant differences in estimated glomerular filtration rate, ejection fraction, or systolic pulmonary artery pressure at 48h. The area under the curve of IRPI at 48h for higher log BNP at discharge &amp;gt; 2.31 at discharge was 0.746 (sensitivity 100%, specificity 48%). Conclusion Early assessment of renal circulation by SMI around 48 hours after ADHF admission may predict congestion resolution at discharge. This underscores the potential utility of SMI in guiding more aggressive decongestive treatment strategies earlier in ADHF.

Increased index of microcirculatory resistance, capillary rarefaction, elevated troponin levels, and their association with transthyretin amyloidosis cardiomyopathy

Abstract Background The pathophysiology of coronary microvascular disease (CMD) in patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM) remains unclear. Objective This study aims to functionally and pathologically assess coronary microvasculature to elucidate the underlying mechanisms of myocardial injury in patients with ATTR-CM. Methods Fifty patients (median age, 74 years; men, n=46, 92%) with echocardiographic evidence of left ventricular hypertrophy (≥12 mm) who underwent endomyocardial biopsy (EMB) and invasive coronary physiological assessments following coronary angiography were enrolled between October 2021 and September 2023 and divided into ATTR-CM (n=30) and non-cardiac amyloidosis (CA) (n=20) groups according to EMB results. All patients with ATTR-CM exhibited positive heart-to-contralateral (H/CL) ratios (&amp;gt;1.5) on technetium 99m pyrophosphate scintigraphy. Fractional flow reserve (FFR), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR) were measured using the PressureWire X guidewire in the left anterior descending artery. Capillary density (/mm2) was determined with EMB tissues by counting the number of CD31 immunopositive luminal structures, whereas the amyloid deposition burden was assessed by measuring the transthyretin immunopositive areas. Circulating cardiac troponin T (hs-cTnT) and brain natriuretic peptide (BNP) were measured. Results Compared to the non-CA group, the ATTR-CM group exhibited lower CFR (2.4±0.3 vs. 3.6±0.4, p=0.01), higher IMR (35.4±3.0 vs. 18.7±3.7, p=0.0009), lower capillary density (255.3±24.9 /mm2 vs. 408.6±29.5 /mm2 , p=0.0002), and elevated hs-cTnT levels (0.056±0.006 ng/mL vs. 0.036±0.004 ng/mL, p=0.01), with similar FFR (0.87±0.015 vs. 0.84±0.013, p=0.1) and BNP levels (229.6±38.1 pg/mL vs. 210.2±46.7 pg/mL, p=0.75). In the overall and ATTR-CM groups, capillary density had no significant correlation with IMR (r=0.16, p=0.41 and r=0.04, p=0.84, respectively) and a significant inverse correlation with hs-cTnT (r=-0.47, p=0.001, and r=-0.48, p=0.009, respectively). In the ATTR-CM group, capillary density was not significantly correlated with the H/CL ratio (r=-0.23, p=0.09); nevertheless, transthyretin immunopositive areas were positively correlated with the H/CL ratio (r=0.47, p=0.01). Conclusion Capillary rarefaction correlates with elevated hs-cTnT levels but not with elevated IMR, and H/CL ratios, suggesting that CMD is involved at the capillary level in ATTR-CM-related myocardial injury independent of the amyloid deposition burden.

Exploring the impact of coronary microvascular dysfunction on cardiac remodeling after st-elevation myocardial infarction

Abstract Background The complex interplay between Coronary Microvascular Dysfunction (CMD) and ST-segment Elevation Myocardial Infarction (STEMI) presents significant clinical hurdles. CMD, commonly seen as a complication following STEMI, is associated with adverse cardiovascular outcomes and persistent anginal symptoms. Despite its clinical relevance, the link between CMD post-STEMI and subsequent left ventricular (LV) diastolic dysfunction, along with functional LV remodelling (FLVR), is yet to be fully explored. Purpose Examine the link between CMD 3 months post-STEMI and its impact on FLVR and diastolic dysfunction. Methods This prospective, observational cohort study focused on STEMI patients. At 3-month post-STEMI, a comprehensive coronary physiology assessment of the culprit artery was conducted using the thermodilution method to measure fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR). CMD was identified with an IMR ≥ 25 or a CFR &amp;lt; 2.0, assuming an FFR &amp;gt; 0.80. Diastolic dysfunction was classified according to ASE/EACVI 2016 guidelines. FLVR was categorized as per Surenjav Chimed et al.'s criteria: Group I with no significant changes in LV size or function, Group II with a decrease in LV ejection fraction (LVEF) greater than 5% without LV dilatation, Group III with an increase in left ventricular end-diastolic volume (LVEDV) ≥ 20%, and Group IV showing both an increase in LVEDV ≥ 20% and a decrease in LVEF over 5%. The study aimed to elucidate the relationship between CMD and the progression of FLVR and diastolic dysfunction, tracked over a 12-month period. Results The study involved 210 patients, mostly men (59.5%), with a median age of 65 (IQR: 58–76). At the 3-month follow-up, CMD was observed in 57 (27.1%) patients. CMD patients had a higher female prevalence (63.2% vs. 32.0%; p &amp;lt; 0.001) and more diabetes (42.1% vs. 17.7%; p &amp;lt; 0.001) compared to non-CMD patients. Both groups shared similar body mass indices, medications, and other risk factors. Laboratory results were similar between groups, except brain natriuretic peptide levels were higher in CMD patients (70.0 vs. 37.0 ng/L; p &amp;lt; 0.001). After 12 months, CMD patients demonstrated significantly less recovery in LVEF (-10.00% vs. 8.00%; p &amp;lt; 0.001), higher prevalence of grade 2 LV diastolic dysfunction (73.08% vs. 1.32%; p &amp;lt; 0.001), and a higher incidence of advanced FLVR (notably in Groups 3 and 4) compared to non-CMD (11.32% vs. 7.28% and 22.64% vs. 1.99%, respectively; p &amp;lt; 0.001). In the adjusted multivariable logistic regression analysis, IMR values independently predicted more severe FLVR and diastolic dysfunction. Conclusions This study highlights that CMD 3 months after STEMI is linked to worse FLVR, diastolic dysfunction, and less recovery in LVEF, emphasizing the need for early CMD detection for better risk assessment. Further research is essential to explore underlying mechanisms and intervention opportunities.LVEF Changes at 12 Months by CMD StatusDiastolic Dysfunction and LV Remodeling