Higher B-type Natriuretic Peptide Research Articles

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<0.001) and all-cause mortality (HR 0.36 [95%CI 0.22-0.60], p<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 <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.

Contemporary implantation protocols enable markedly lower pacemaker rate for selfexpandable TAVR

Abstract Background Even in a low-risk cohort, the Evolut low-risk trial has reported a still rather high pacemaker implantation rate over 20%. In the recent years, contemporary implantation protocols have been introduced aiming on a higher implantation position. Purpose Data on a reduction of pacemaker rate in contemporary implantation practice is still limited. Methods We retrospectively analyzed baseline-characteristics and pacemaker-implantation rates after TAVR in patients being treated with a Medtronic Evolut Prosthesis for aortic valve stenosis in our center in the years 2018 (conventional implantation in 3-cusp view) vs. 2023 (contemporary implantation in cusp overlap technique). Results 160 Patients were retrospectively included. We found out, that contemporary implantation lead to a marked reduction of pacemaker rate (8.7 vs. 20.9%, p=0.047; HR 0.36[IQR 0.14-0.96; p=0.041]). While most baseline-parameters including age (83.5 (79.2/87.3) vs. 82.8 (79.4/86.2), p=0.654), LVEF (55.0 (54.3/57.8) vs. 55.0 (51.0/59.0), p=0.992) and overall risk score (Euroscore II 3.5 (2.5/4.7) vs. 3.6 (2.3/5.7), p= 0.726) had no relevant impact on pacemaker rate, female patients were less prone to receive a pacemaker (8.6% vs. 21.3%, p=0.030). Of all conduction disturbances before procedure, a pre-existing RBBB was strongly associated with a relevantly higher pacemaker rate (50.0% vs. 11.3% (p<0.001), HR 7.88 (IQR 2.73/22.74; p<0.001)). Furthermore, more severe leaflet calcification (p=0.049), a deeper implantation depth (6.0 (5.0/6.5) vs. 5.0 (4.0/60.), p=0.042), larger annular dimensions (perimeter 79.7 (75.2/87.7) 76.8 (71.9/80.7), vs. p=0.047) and prostheses sizes (Evolut 34 vs. smaller sizes 28.1 vs. 12.5%, p=0.053), higher BNP (547 (314/1488) vs. 396 (208/856)), p=0.039 and body weight (78.0 (71.3/90.0) vs. 73.0 (63.5/84.5), p=0.030) were attributed to a higher pacemaker rate. Conclusions In our retrospective database we demonstrated that a contemporary implantation protocol enabling higher implantation position leads to a significant reduction in pacemaker rate, even in the high-risk collective of patients with pre-existing RBBB (58.3 vs. 15.2%, p=0.002 compared to 33.3 vs. 6.3%, p=0.081).

Association between BNP and all-cause mortality in critically ill children: a cohort study.

There is evidence that a high level of BNP is associated with poorer outcomes in patients with cardiac diseases, but few data are available concerning BNP and all-cause mortality in pediatric population. Using the 2010-2018 pediatric intensive care database, we conducted a retrospective study on patients aged 28 days to 18 years, analyzing post-admission BNP measurements. Through two-piecewise regression to identify inflection points, and multivariable logistic regression, we investigated BNP's association with all-cause mortality. We also developed a multivariable-adjusted restricted cubic spline model to explore BNP's non-linear correlation with mortality. In a study of 3220 patients, the overall all-cause mortality rate was 6.7%, with rates across BNP quartiles (Q1-Q4) significantly differing, highlighting a notable increase in mortality at higher BNP levels (P < 0.001). Specifically, patients with BNP ≥ 10,170 pg/ml had an adjusted mortality odds ratio (OR) of 2.017 (95% CI 1.265-3.217; P = 0.0032). Analysis confirmed a non-linear relationship between BNP levels and mortality, with log2 BNP associated with increased risk (OR1.28, 95% CI 1.19-1.38; P < 0.001). Subgroup analyses further revealed that very high BNP levels, especially in infants, with lactate ≥2.0 mmol/L, or CKMB ≥ 45 μ/L. BNP level was associated with all-cause mortality, especially for the patients with BNP ≥ 10,170 pg/ml. This study explored the non-linear association between BNP levels and all-cause mortality in the PICU, finding a significant association among patients with BNP levels above 10,170 pg/ml. The study revealed that higher BNP levels are associated with increased mortality in critically ill children, including those with non-cardiac diseases. This research provides new data on a Southern Chinese population, previously unstudied, enriching the existing body of knowledge. While most studies have focused on adult cardiac patients, this research highlights the importance of BNP as a prognostic tool in the PICU, including non-cardiac cases, adding to the literature. This study furnishes novel clinical evidence supporting the monitoring of BNP concentrations within the PICU, aiding in prognostic predictions and the development of tailored treatment plans for patients.

Elevated B-Type Natriuretic Peptide Level as a Residual Risk Factor for Ventricular Arrhythmias Among Patients Undergoing Cardiac Resynchronization Therapy With Improved Left Ventricular Ejection Fraction.

Patients who achieve improved left ventricular ejection fraction (LVEF >35%) with cardiac resynchronization therapy (CRT) are at a lower risk of ventricular arrhythmia (VA). Little is known about the significance of the B-type natriuretic peptide (BNP) level for the risk of VA. This study investigated the risk factors for VA in CRT and the risk stratification of VA with BNP in CRT with improved LVEF. This study evaluated 352 CRT patients from 2012 to 2020. Patients were categorized into 2 groups: improved LVEF (impEF; LVEF >35%), and low LVEF (lowEF; LVEF ≤35%). The serum BNP levels 6 months after CRT device implantation were measured. The primary endpoint was defined as VA requiring treatment with anti-tachycardia pacing or shock or persisting for ≥30 s. Overall, 102 patients had improved LVEF. The impEF group had a significantly lower VA risk than the lowEF group. Patients with low BNP had a lower VA risk than those with high BNP; however, no significant difference was observed between patients with high BNP and those in the lowEF group. Univariate analysis revealed that high BNP was a predictor of VA in the impEF group. The VA risk is reduced with improved LVEF after CRT but not with high BNP levels. The post-BNP level after CRT implantation is a useful marker for predicting VA in patients with improved LVEF.

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.

The Relative Apical Sparing Strain Pattern in Severe Aortic Valve Stenosis: A Marker of Adverse Cardiac Remodeling.

The presence of a relative apical sparing (RAS) echocardiographic strain pattern raises a suspicion of underlying cardiac amyloidosis (CA). However, it is also increasingly observed in patients with aortic stenosis (AS). We aimed to evaluate the prevalence, dynamics, and clinical characteristics of the RAS strain pattern in severe AS patients who had been referred for surgical aortic valve replacement (SAVR). A total of 77 patients with severe AS and without CA were included with a mean age of 70 (62-73) years, 58% female, a mean aortic valve area index of 0.45 ± 0.1 cm2/m2, and a mean gradient of 54.9 (45-70) mmHg. An RAS strain pattern was detected in 14 (18%) patients. RAS-positive patients had a significantly higher LV mass index (125 ± 28 g/m2 vs. 91 ± 32, p = 0.001), a lower LV ejection fraction (62 ± 12 vs. 68 ± 13, p = 0.040), and lower global longitudinal strain (-14.9 ± 3 vs. -18.7 ± 5%, p = 0.002). RAS strain pattern-positive patients also had higher B-type natriuretic peptide (409 (161-961) vs. 119 (66-245) pg/L, p = 0.032) and high-sensitivity troponin I (15 (13-29) vs. 9 (5-18) pg/L, p = 0.026) levels. Detection of an RAS strain pattern was strongly associated with increased LV mass index (OR 1.03, 95% CI 1.01-1.06, p < 0.001). The RAS strain pattern had resolved in all patients by 3 months after SAVR. Our findings suggest that the RAS strain pattern can be present in patients with severe AS without evidence of CA. The presence of an RAS strain pattern is associated with adverse LV remodeling, and it resolves after SAVR.

Neutrophil Extracellular Traps in Myocardial Tissue Drive Cardiac Dysfunction and Adverse Outcomes in Patients With Heart Failure With Dilated Cardiomyopathy.

The immune systems and chronic inflammation are implicated in the pathogenesis of dilated cardiomyopathy (DCM) and heart failure. However, the significance of neutrophil extracellular traps (NETs) in heart failure remains to be elucidated. We enrolled consecutive 62 patients with heart failure with idiopathic DCM who underwent endomyocardial biopsy. Biopsy specimens were subjected to fluorescent immunostaining to detect NETs, and clinical and outcome data were collected. Ex vivo and in vivo experiments were conducted. The numbers of NETs per myocardial tissue area and the proportion of NETs per neutrophil were significantly higher in patients with DCM compared with non-DCM control subjects without heart failure, and the numbers of NETs were negatively correlated with left ventricular ejection fraction. Patients with DCM with NETs (n=32) showed lower left ventricular ejection fraction and higher BNP (B-type natriuretic peptide) than those without NETs (n=30). In a multivariable Cox proportional hazard model, the presence of NETs was independently associated with an increased risk of adverse cardiac events in patients with DCM. To understand specific underlying mechanisms, extracellular flux analysis in ex vivo revealed that NETs-containing conditioned medium from wild-type neutrophils or purified NET components led to impaired mitochondrial oxygen consumption of cardiomyocytes, while these effects were abolished when PAD4 (peptidyl arginine deiminase 4) in neutrophils was genetically ablated. In a murine model of pressure overload, NETs in myocardial tissue were predominantly detected in the acute phase and persisted throughout the ongoing stress. Four weeks after transverse aortic constriction, left ventricular ejection fraction was reduced in wild-type mice, whereas PAD4-deficient mice displayed preserved left ventricular ejection fraction without inducing NET formation. NETs in myocardial tissue contribute to cardiac dysfunction and adverse outcomes in patients with heart failure with DCM, potentially through mitochondrial dysfunction of cardiomyocytes.

Quantifying Hemodynamic Cardiac Stress and Cardiomyocyte Injury in Normotensive and Hypertensive Acute Heart Failure.

The characterization of the different pathophysiological mechanisms involved in normotensive versus hypertensive acute heart failure (AHF) might help to develop individualized treatments. The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring the B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT) concentrations in 1152 patients presenting with centrally adjudicated AHF to the emergency department (ED) (derivation cohort). AHF was classified as normotensive with a systolic blood pressure (SBP) of 90-140 mmHg and hypertensive with SBP > 140 mmHg at presentation to the ED. Findings were externally validated in an independent AHF cohort (n = 324). In the derivation cohort, with a median age of 79 years, 43% being women, 667 (58%) patients had normotensive and 485 (42%) patients hypertensive AHF. Hemodynamic cardiac stress, as quantified by the BNP and NT-proBNP, was significantly higher in normotensive as compared to hypertensive AHF [1105 (611-1956) versus 827 (448-1419) pg/mL, and 5890 (2959-12,162) versus 4068 (1986-8118) pg/mL, both p < 0.001, respectively]. Similarly, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF [41 (24-71) versus 33 (19-59) ng/L, p < 0.001]. A total of 313 (28%) patients died during 360 days of follow-up. All-cause mortality was higher in patients with normotensive AHF vs. patients with hypertensive AHF (hazard ratio 1.66, 95%CI 1.31-2.10; p < 0.001). Normotensive patients with a high BNP, NT-proBNP, or hs-cTnT had the highest mortality. The findings were confirmed in the validation cohort. Biomarker profiling revealed a higher extent of hemodynamic stress and cardiomyocyte injury in patients with normotensive versus hypertensive AHF.

Clinical Features and Multimodality Diagnostic Tools of Pulmonary Hypertension

Pulmonary hypertension (PH) is defined as an increase in mean pulmonary arterial pressure (mPAP) above normal (&gt; 20 mmHg) and an increase in pulmonary vascular resistance (pulmonary vascular resistance / PVR) above normal in resting settings. The pathophysiology of PH involves remodeling of the pulmonary vessels, from the main pulmonary arteries, lobar arteries, segmental arteries, distal arteries, pulmonary arterioles, capillaries to the postcapillary pulmonary veins. In general, the epidemiological figures for PH are not known with certainty. The United Kingdom reported a PH prevalence of 97 cases per one million people, with a female-to-male ratio of 1.8. The diagnostic strategy for PH focuses primarily on two issues. The primary objective is to improve the early detection of PH and expedite the transfer of patients at high risk for PAH, CTEPH, or other forms of severe PH to a PH center. The second objective is to identify the underlying disease, including left heart disease (Group 2 PH) and lung disease (Group 3 PH), as well as comorbidities, in order to assure proper classification, risk assessment, and therapy. The gold standard for detecting and categorizing pulmonary hypertension is right heart catheterization (RHC). Clinical scoring in the form of shortness of breath without any obvious cause accompanied by physical examination, ECG and Thorax X-ray images which depict an enlarged right heart have good specificity and sensitivity for the diagnosis of pulmonary hypertension in patients with congenital heart disease. A high right ventricular pressure, mean PAP, and BNP values during observation, as well as heart size on chest X-ray can be predictors of a poorer prognosis in this population. Keyword: Clinical Risk Scoring, Pulmonary Hypertension, Right Heart Catheterization.

Patterns of atrial fibrillation, relevant cardiac structural and functional changes predict functional and cognitive outcomes in patients with ischemic stroke and atrial fibrillation

BackgroundAtrial fibrillation (AF) pattern, relevant cardiac changes are important predictors of outcomes in AF, but their impact on patients with ischemic stroke and AF remained unclear. We aimed to explore the impact of AF patterns, cardiac structural and functional markers on long-term functional and cognitive outcomes in ischemic stroke patients with AF. MethodsIschemic stroke patients diagnosed with AF were enrolled in this retrospective cohort study. AF pattern was defined by both traditional and novel classification, in which patients were divided into AF diagnosed after stroke (AFDAS) and known before stroke (KAF). Left atrial (LA) diameter, left ventricular ejection fraction (LVEF), natriuretic peptide (BNP) and cardiac troponin (cTnI) were dichotomized according to the median value. Outcomes include poor functional outcome and cognitive impairment at the 1-year follow-up. Multivariable logistic regression was performed to validate the association between AF pattern, parameters of cardiac change and functional and cognitive outcome. ResultsA total of 377 patients were included. Non-paroxysmal AF patients had a higher risk of poor functional outcome (OR = 3.59, P < 0.0001) and cognitive impairment (OR = 2.38, P = 0.019) than paroxysmal AF patients, while there were no differences between AFDAS and KAF. Lower LVEF (OR = 1.83, P = 0.045) and higher BNP (OR = 2.66, P = 0.001) were associated with poor functional outcome. Lower LVEF (OR = 2.86, P = 0.004), higher LA diameter (OR = 2.72, P = 0.008) and BNP (OR = 2.31, P = 0.023) were associated with cognitive impairment. ConclusionsAF type and related cardiac markers can serve as predictors for poor functional and cognitive outcomes. Comprehensive cardiac assessment and monitoring should be strengthened after stroke.

Urinary Immunoglobulin G Is a Novel Biomarker for Atherosclerotic Burden in Mild Acute Ischemic Stroke Patients.

Urinary immunoglobulin G (IgG) may be a stronger marker of atherosclerosis than microalbuminuria are because urinary IgG reflects proteinuria level and size-selectivity loss. Microalbuminuria-not urinary IgG-is associated with mild acute ischemic stroke (MAIS). Using the Jikei University School of Medicine Stroke Registry, we selected and screened patients with symptomatic acute ischemic stroke (onset-to-door time ≤ 24 h). The exclusion criteria were (1) on-admission NIHSS scores ＞10, (2) a modified Rankin Scale (mRS) score ≥ 2 prior to stroke onset, (3) incomplete data (no urinalysis ≤ 3 days after admission or no mRS score at 90 days from stroke onset), and (4) an active malignancy. Patients at 90 days post-discharge were divided into those with favorable mRS scores of 0-1 and those with unfavorable mRS scores of 2-6. Clinical backgrounds were compared for (1) patients with positive and negative urinary IgG results, and (2) patients with favorable and unfavorable outcomes. Of our study's 210 patients (164=male, median age=68, median eGFR=53.2 ml/min/1.73 m2), 30 (14%) presented with positive urinary IgG, which was associated with cardiovascular risk factors. Higher BNP, higher D-dimer, lower eGFR, and higher CAVI were associated with higher positive urinary IgG. The favorable group, comprising 155 (74%) patients, had higher negative urinary IgG than the unfavorable group (89% vs 76%, P=0.026). No statistical difference emerged regarding microalbuminuria (29% vs 29%, P=1.000). In MAIS, urinary IgG was associated with both the presence of atherosclerosis and an unfavorable outcome at 90 days after stroke onset.

A new staging system using right atrial strain in patients with immunoglobulin light-chain cardiac amyloidosis.

There are minimal data on the prognostic impact of right atrial strain during the reservoir phase (RASr) in patients with immunoglobulin light-chain (AL) cardiac amyloidosis. Among 78 patients who were diagnosed with AL cardiac amyloidosis at Kumamoto University Hospital from 2007 to 2022, 72 patients with sufficient two-dimensional speckle tracking imaging data without chemotherapy before the diagnosis were retrospectively analysed. During a median follow-up of 403days, 31 deaths occurred. Age and the rate of male sex were not significantly different between the all-cause death group and the survival group (age, 70.4±8.8years vs. 67.0±10.0years, P=0.14, male sex, 65% vs. 66%, P=0.91). The estimated glomerular filtration rate (eGFR) was significantly lower, and B-type natriuretic peptide (BNP) and high sensitivity cardiac troponin T (hs-cTnT) were significantly higher, in the all-cause death group versus the survival group (eGFR, 48.2±21.0mL/min/1.73m2 vs. 59.4±24.4mL/min/1.73m2, P<0.05, BNP, 725 [360-1312] pg/mL vs. 123 [81-310] pg/mL, P<0.01, hs-cTnT, 0.12 [0.07-0.18] ng/mL vs. 0.05 [0.03-0.08] ng/mL, P<0.01). Left ventricular (LV) global longitudinal strain (GLS) (LV-GLS), left atrial strain during the reservoir phase (LASr), right ventricular GLS (RV-GLS), and RASr were significantly lower in the all-cause death group versus the survival group (LV-GLS, 8.5±4.3% vs. 11.8±3.8%, P<0.01, LASr, 8.8±7.1% vs. 14.3±8.1%, P<0.01, RV-GLS, 11.6±5.1% vs. 16.4±3.9%, P<0.01, RASr, 10.2±7.3% vs. 20.7±9.5%, P<0.01). RASr was significantly associated with all-cause death after adjusting for RV-GLS, LV-GLS and LASr (hazard ratio [HR]: 0.91, 95% confidence interval [95% CI]: 0.83-0.99, P<0.05). RASr and log-transformed BNP were significantly associated with all-cause death after adjusting for log-transformed troponin T and eGFR (RASr, HR: 0.93, 95% CI: 0.87-1.00, P<0.05; log-transformed BNP, HR: 2.10, 95% CI: 1.17-3.79, P<0.05). The optimal cut-off values were RASr: 16.4% (sensitivity: 66%, specificity: 84%, area under curve [AUC]: 0.81) and BNP: 311.2pg/mL (sensitivity: 83%, specificity: 78%, AUC: 0.82) to predict all-cause mortality using ROC analysis. Kaplan-Meier analysis revealed that patients with low RASr (<16.4%) or high BNP (>311.2pg/mL) had a significantly high probability of all-cause death (both, P<0.01). We devised a new staging score by adding 1 point if RASr decreased or BNP levels increased more than each cut-off value. The HR for all-cause death using score 0 as a reference was 5.95 (95% CI: 1.19-29.79; P<0.05) for score 1 and 23.29 (95% CI: 5.37-100.98; P<0.01) for score 2. The new staging system using RASr and BNP predicted prognosis in patients with AL cardiac amyloidosis.

Baseline Echocardiography and Laboratory Findings in MIS-C and Associations with Clinical Illness Severity.

Children with COVID-associated multisystem inflammatory syndrome (MIS-C) may develop severe disease. We explored the association of admission echocardiographic and laboratory parameters with MIS-C disease severity.This retrospective, single center study of consecutive MIS-C patients (4/2020-12/2021) excluded those with preexisting cardiomyopathy, congenital heart disease, or prior cardiotoxic therapy. Our hypothesis was that worse admission echocardiographic and laboratory parameters were associated with more severe disease based on vasoactive medication use. Univariable and multivariable logistic regression models assessed the association between vasoactive medication use and baseline variables.Of 118 MIS-C patients, median age was 7.8 years (IQR 4.6, 11.8), 48% received vasoactive medication. Higher admission brain natriuretic peptide [OR 1.07 (95% CI 1.02,1.14), p = 0.019], C-reactive protein [OR 1.08 (1.03,1.14), p = 0.002], troponin [OR 1.05 (1.02,1.1), p = 0.015]; lower left ventricular ejection fraction [LVEF, OR 0.96 (0.92,1), p = 0.042], and worse left atrial reservoir strain [OR 0.96 (0.92,1), p = 0.04] were associated with vasoactive medication use. Only higher CRP [OR 1.07 (1.01, 1.11), p = 0.034] and lower LVEF [0.91 (0.84,0.98), p = 0.015] remained independently significant. Among those with normal admission LVEF (78%, 92/118), 43% received vasoactive medication and only higher BNP [OR 1.09 (1.02,1.19), p = 0.021 per 100 pg/mL] and higher CRP [OR 1.07 (1.02,1.14), p = 0.013] were associated with use of vasoactive medication.Nearly half of all children admitted for MIS-C subsequently received vasoactive medication, including those admitted with a normal LVEF. Similarly, admission strain parameters were not discriminatory. Laboratory markers of systemic inflammation and cardiac injury may better predict early MIS-C disease severity.

Sex differences in the nutritional status and its association with long-term prognosis in patients with heart failure with reduced ejection fraction: a prospective cohort study.

Many studies show the association between malnutrition and poor prognosis in heart failure (HF) patients. Our research aimed to analyse sex differences in patients with HF with reduced ejection fraction (HFrEF), emphasizing nutritional status and the influence of selected parameters on the prognosis. We enrolled 276 consecutive patients diagnosed with HFrEF. Nutritional status was assessed using Mini Nutritional Assessment (MNA), geriatric nutritional risk index (GNRI), and body mass index (BMI). The mean follow-up period was 564.4 ± 346.3 days. The analysed group included 81.2% of men. The median age was 58, interquartile range (IQR) 49-64 years. Among all patients, almost 60% were classified as NYHA III or IV. Half of the participants were at risk of malnutrition, and 2.9% were malnourished. During follow-up, 72 (26.1%) patients died. The female sex was not associated with a higher occurrence of malnutrition (P = 0.99) or nutritional risk (P = 0.85), according to MNA. Coherently, GNRI scores did not differ significantly between the sexes (P = 0.29). In contrast, BMI was significantly higher in males (29.4 ± 5.3 vs. 25.9 ± 4.7; P < 0.001). Impaired nutritional status assessed with any method (MNA, GNRI, BMI) was not significantly associated with a worse prognosis. In multivariable analysis, NYHA class, lower estimated glomerular filtration rate, higher B-type natriuretic peptide (BNP), higher N-terminal fragment of proBNP, and higher uric acid were independent of sex and age predictors of all-cause mortality. There were no sex differences in the nutritional status in the HFrEF patients, apart from lower BMI in females. Impaired nutritional status was not associated with mortality in both men and women.

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.

Phenogroups and Their Prognosis of Acute Decompensated Heart Failure with Preserved Ejection Fraction.

Acute heart failure is an important cause of unplanned hospitalizations and poses a significant burden through increased mortality and frequent hospitalizations. Heart failure with preserved ejection fraction (HFpEF) presents as a diverse condition characterized by complex cardiovascular and non-cardiovascular pathology. This study aimed to identify distinct clinical phenotypes in acute decompensated HFpEF (ADHF) using cluster analysis and assess their prognostic significance. We applied a latent class analysis to 1,281 ADHF patients admitted to a single cardiac intensive care unit between 2008 and 2022 with a left ventricular ejection fraction ≥ 50%. We used 83 factors obtained at hospitalization. We evaluated the association between phenogroups and clinical outcomes using either Cox regression model or Fine-Gray competing risk model. We identified 4 phenogroups: Phenogroup 1 (n = 133, 10%) included younger patients with metabolic disorders and a low level of B-type natriuretic peptide (BNP); Phenogroup 2 (n = 346, 27%) had systemic congestion and high BNP levels; Phenogroup 3 (n = 514, 40%) had multiple comorbidities and vascular disorders; Phenogroup 4 (n = 288, 22%) included older patients with bradyarrhythmia and atrial fibrillation. After adjusting for age, sex, and Get with the Guidelines-Heart Failure risk score, Phenogroup 2 had the highest risk of all-cause death and cardiac death. In conclusion, we identified 4 clinically relevant phenogroups of ADHF patients, each associated with different adverse outcomes. Phenotyping may provide a better understanding of the underlying mechanisms involved in the heterogeneity of ADHF and decompensation. Furthermore, it may facilitate the search for phenotype-specific therapeutic strategies.

Concurrent Negative Impact of Undernutrition and Heart Failure on Functional and Cognitive Recovery in Hip Fracture Patients.

Evidence on the effects of frailty, undernutrition, and heart failure (HF) on patients with hip fractures is scarce. This retrospective cohort study aimed to examine the effects of undernutrition and HF on outcomes in patients who underwent convalescent rehabilitation after hip fracture. Undernutrition was defined as body mass index (BMI) < 20.0 (Low BMI). Heart failure (HF) was defined as a B-type natriuretic peptide (BNP) > 100 (High BNP). The study outcomes included the Functional Independence Measure motor domain (FIM-motor) and cognitive domain (FIM-cognition) at discharge. To consider the effects of low BMI, high BNP, and the simultaneous presence of both ("low BMI and high BNP"), we used multivariate linear regression analyses to examine whether these were associated with the outcomes. A total of 110 (mean age 87.4 years, 24.8% male) were analyzed. As a result, low BMI (β = -0.088, p = 0.027) and high BNP (β = -0.053, p = 0.015), each alone, were significantly associated with the FIM motor at discharge, whereas the simultaneous presence of "low BMI and high BNP" was significantly associated with the FIM motor at discharge, while the strength of the association was greater than each association alone (β = -0.152, p = 0.010). Further, the simultaneous presence of "low BMI and high BNP" was significantly associated with FIM cognition at discharge (β = -0.109, p = 0.014). Comprehensive multidisciplinary management is needed, including preoperative or early postoperative nutritional support and rehabilitation, followed by rehabilitation nutrition care management, in patients with hip fracture.

Impact of heart failure severity and major bleeding events after percutaneous coronary intervention on subsequent major adverse cardiac events

Abstract Background Heart failure (HF) is one of high bleeding risk after percutaneous coronary intervention (PCI). Furthermore, major bleeding events increase the risk of subsequent cardiovascular events. However, it is unknown whether HF severity and bleeding events are associated with major adverse cardiac events (MACE). Purpose The aim of this study was investigating the impact of HF severity or bleeding events on subsequent MACE. Methods Clinical Deep Data Accumulation System (CLIDAS), a multicenter database with 7 tertiary medical hospitals, was developed to collect data directly for patient characteristics, medications, laboratory test, physiological test, cardiac catheterization and PCI treatment in electronic medical records. This retrospective analysis included 7,160 patients with PCI between April 2014 and March 2020 and have completed 3-year follow-up. The patients were divided into two groups: HF with high BNP (HF-hBNP) (&amp;gt;100 pg/ml) (n=384) and non-HF-hBNP (HF with low BNP and non-HF) (n=6,776). Furthermore, both groups were re-classified into two groups according to presence of major bleeding events in 30 days: HF-hBNP with 30-day bleeding (n=14), without 30-day bleeding (n=370), non-HF-hBNP with 30-day bleeding (n=74) and without 30-day bleeding (n=6,702). Primary endpoint was defined as MACE. Results HF with high BNP was an independent risk factor of MACE (hazard ratio [HR], 2.21; 95% confidence interval [CI], 1.64-2.98) compared with non-HF. Among the HF-hBNP patients, MACE incidence tended to be increased by 30-day bleeding (p=0.075). In addition, among the non-HF-hBNP patients, the bleeding events increased the risk of MACE (p=0.003). The multivariable Cox regression model revealed that other three groups were associated with a high risk compared with non-HF-hBNP without 30-day bleeding group: non-HF-hBNP with 30-day bleeding (HR, 3.90; 95% CI, 1.59-9.54), HF-hBNP without 30-day bleeding (HR, 2.19; 95% CI, 1.56-3.07) and HF-hBNP with 30-day bleeding (HR, 8.33; 95% CI, 2.57-27.0). Conclusion The real-world database CLIDAS revealed that HF with high BNP and major bleeding events in 30 days might be associated with MACE. Those results suggest that management of HF and prevention of bleeding complication in early days after PCI could be important to prevent MACE.

Outcome of transcatheter mitral valve repair in heart failure patients with reduced ejection fraction and severe left ventricular dilatation

Abstract Introduction The COAPT trial demonstrated the benefit of transcatheter edge­to­edge mitral valve repair (TEER) for heart failure patients who had reduced ejection fraction (HFrEF) with symptomatic secondary mitral regurgitation (MR). However, patients with severe left ventricular (LV) dilatation were not included in the COAPT trial. Furthermore, disproportionate LV dilatation was suggested as a possible explanation for the lack of benefit in the MITRA­FR trial. Purpose The purpose of this study was to assess the safety and efficacy of TEER in HFrEF patients with severe LV dilatation. Methods We studied 75 HFrEF patients who underwent mitral valve repair between 2018-2021. Reduced LV ejection fraction (LVEF) was defined as LVEF of 40% or less. These patients were categorized with and without severe LV dilatation based on left ventricular end-diastolic volume index (LVEDVI) using a median cut­off value of &amp;gt;139ml/m2 in men and &amp;gt;128cm/m2 in women. Results There were 37 patients with severe LV dilatation (D) and 38 without (ND). Median LVEDVI was 172 [149-190] ml/m2 in the D group vs 120 [105-127] ml/m2 in the ND group. Compared to the ND patients, patients with severe LV dilatation were more treated with SGLT2-inhibitor (rate 24% vs 3%), had lower LVEF (30 [25-31] % vs 32 [30-36] %), and higher BNP (1160 [683-2586] vs 619 [396-1253] pg/ml). There was no significant difference in MR grade (4 [3-4] vs 4 [3-4]), EROA (0.32 [0.22-0.66] vs 0.34 [0.24-0.48] cm2), NYHA class (3 [2-4] vs 3 [2-3]) and mean systolic pulmonary pressure (31 [20-43] vs 34 [25-41] mmHg). Peri­procedural adverse events were rare in both groups. 1 patient had pseudoaneurysm in the ND group, and 1 patient had cardiogenic shock and 1 patient had stroke after the procedure in the D group. At discharge, there was marked improvement in MR grade (1 [1-2] vs 1 [1-2] for both). D group had a tendency of higher reduction in LVEDVI (-12 [-24--1] vs -5[-13-4] ml/m2) than ND group. BNP level of the D group had a significantly higher degree of decline before discharge (-458 [-141--1566] to -102 [+51--306] pg/ml) than that of ND group. No differences were noted in mortality between two groups (Figure). Conclusion TEER in HFrEF patients with severe LV dilatation seems to provide similar outcomes compared to patients with less severe dilatation. Further studies are needed to clarify the indication and establish the effectiveness of TEER in these patients.

Efficacy of bepridil as a periprocedural support drug in atrial fibrillation patients with left ventricular systolic dysfunction undergoing catheter ablation

Abstract We previously reported that sinus restoration either with drugs or DC cardioversion prior to catheter ablation (CA) was associated with a better outcome in persistent atrial fibrillation (AF). As an antiarrhythmic agent for persistent AF, amiodarone is recommended for patients with structural heart disease. Bepridil, a unique multichannel inhibitor, has a comparable defibrillation efficacy and fewer extracardiac complications than amiodarone, although safety and efficacy of bepridil has not been established in those with left ventricular (LV) systolic dysfunction. We compared the safety and efficacy of bepridil and amiodarone as periprocedural support drugs for CA in patients with persistent AF with LV systolic dysfunction. Method and result: Persistent AF patients with LVEF ≤50% taking bepridil or amiodarone as periprocedural support drugs for CA were retrospectively analyzed; 51 patients in the bepridil group and 17 patients in the amiodarone group. There were 20 (39%) in the bepridil group and 17 (100%) in the amiodarone group with LVEF less than 40%. The amiodarone group had more history of heart failure hospitalizations, higher BNP, and lower LVEF than the bepridil group (HF; Bep 35.8% vs Amio 94.1% [p&amp;lt;0.01], BNP; Bep 306.4±422.8 pg/ml vs Amio 645.2±456.3 [p&amp;lt;0.01], LVEF; Bep 39.9±8.4% vs Amio 26.7±7.9% [p&amp;lt;0.01]). Bepridil was used at a dose of 126±39 mg and amiodarone at 153±60 mg before CA. Successful pharmacological defibrillation before CA was more prevalent in the bepridil group (Bep; 15:29.4% vs Amio; 2:11.8%, p=0.14). The time from drug induction to CA was 41±38 days in the bepridil group and 66±59 days in the amiodarone group. At 1-year after CA, doses of both drugs could be reduced (Bep: 72±53mg, Amio: 67±49mg), and 12 (23.5%) in the bepridil group and 3 (17.6%) in the amiodarone group were able to discontinue the drug. AF recurred in 6 (11%) in the bepridil group, and 2 (11%) in the amiodarone group. QTc was the longest immediately before CA in the both groups (Bep: 462±36ms, Amio: 462±32ms), but was shortened at 1-year with the drug dose reduction (Bep: 435±40ms, Amio: 444±29ms). LVEF significantly improved following maintenance of sinus rhythm in the both groups (Bep: 39.9±8.4% to 52.6±10.2% [p&amp;lt;0.01], Amio: 26.7±7.9% to 49.5±14.5% [p&amp;lt;0.01]), which was comparable between the 2 groups. Fatal ventricular arrhythmia occurred in 1 (5%) in the amiodarone group but not in the bepridil group. Hospitalization for heart failure occurred in 2 (3.9%) in the bepridil group. Discussion: Bepridil could be used safely at a short-term high dose before ablation and then reducing the dose after ablation. There is also a trend toward selecting bepridil in patients with relatively preserved cardiac function and less severe conditions. Conclusion: Bepridil can be used rather safely in AF patients with LV systolic dysfunction undergoing CA as a periprocedural support drug.