N-terminal pro-B Natriuretic Peptide Research Articles

The effect of sustained-release CARvedilol in patients with hypErtension and heart failure with preserved ejection fraction: a study protocol for a pilot randomized controlled trial (CARE-preserved HF).

Although beta-blockers improve clinical outcomes in heart failure with reduced ejection fraction, the benefit of beta-blockers in heart failure with preserved ejection fraction (HFpEF) is uncertain. Global longitudinal strain (GLS) is a robust predictor of heart failure outcomes, and recent studies have shown that beta-blockers are associated with improved survival in those with low GLS (GLS <14%) but not in those with GLS ≥14% among patients with LVEF ≥40%. Therefore, the objective of this trial is to evaluate the effect of sustained-release carvedilol (carvedilol-SR) on the outcome [N-terminal pro-B-natriuretic peptide (NT-proBNP) concentration] in patients with hypertension and HFpEF and will assess the differential effects of these drugs on the outcome, according to the GLS categories. This prospective randomized double-blind multicenter trial (CARE-preserved HF) will include 100 patients with HFpEF from three tertiary hospitals in South Korea. Patients with HFpEF and hypertension aged ≥20 years who have evidence of functional and structural heart disease on echocardiography and elevated natriuretic peptide will be enrolled. Eligible participants will be randomized 1:1 to either the carvedilol-SR group (n = 50) or the placebo group (n = 50). Patients in the carvedilol-SR group will receive 8, 16, 32, or 64 mg carvedilol-SR once daily for 6 months, and the dose of carvedilol will be up-titrated at the discretion of the treating physicians. The primary efficacy outcome was the time-averaged proportional change in N-terminal pro-B-natriuretic peptide concentration from baseline to months 3 and 6. We will also evaluate the differential effects of carvedilol-SR on primary outcomes according to GLS, using a cut-off of 14% or the median value. This randomized controlled trial will investigate the efficacy and safety of carvedilol-SR in patients with HFpEF and hypertension. ClinicalTrial.gov, identifier NCT05553314.

Prognostic Factors for Cardiotoxicity among Children with Cancer: Definition, Causes, and Diagnosis with Omics Technologies.

Improvements in the treatment of childhood cancer have considerably enhanced survival rates over the last decades to over 80% as of today. However, this great achievement has been accompanied by the occurrence of several early and long-term treatment-related complications major of which is cardiotoxicity. This article reviews the contemporary definition of cardiotoxicity, older and newer chemotherapeutic agents that are mainly involved in cardiotoxicity, routine process diagnoses, and methods using omics technology for early and preventive diagnosis. Chemotherapeutic agents and radiation therapies have been implicated as a cause of cardiotoxicity. In response, the area of cardio-oncology has developed into a crucial element of oncologic patient care, committed to the early diagnosis and treatment of adverse cardiac events. However, routine diagnosis and the monitoring of cardiotoxicity rely on electrocardiography and echocardiography. For the early detection of cardiotoxicity, in recent years, major studies have been conducted using biomarkers such as troponin, N-terminal pro b-natriuretic peptide, etc. Despite the refinements in diagnostics, severe limitations still exist due to the increase in the above-mentioned biomarkers only after significant cardiac damage has occurred. Lately, the research has expanded by introducing new technologies and finding new markers using the omics approach. These new markers could be used not only for early detection but also for the early prevention of cardiotoxicity. Omics science, which includes genomics, transcriptomics, proteomics, and metabolomics, offers new opportunities for biomarker discovery in cardiotoxicity and may provide an understanding of the mechanisms of cardiotoxicity beyond traditional technologies.

Comparison of medical care and long-term mortality in two cohorts of patients 10 years apart with chronic coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Bundesministerium für Bildung und Forschung. Background and introduction Cardiovascular diseases (CVD) remain the most common cause of death, although mortality due to CVD in Germany has decreased continuously over the past 20 years. The reasons for this decline are manifold. Besides the identification of risk factors, the application of algorithms for risk stratification, and the promotion of preventive means, the improvement in treatment strategies was of crucial importance [1, 2]. The ABC-CHD risk model combines novel biomarkers such as N-terminal pro-B-natriuretic peptide (NT-proBNP) and cardiac troponin T (hs-cTnT) with conventional factors in a unifying risk score which has been shown to reliably assess risk for CV mortality in patients with chronic coronary syndrome (CCS) [3]. However, data from the tertiary prevention setting, comparing its performance during different time periods, are scarce. Aims This study aimed to describe the characteristics and mortality of two cohorts of patients with CCS with identical study designs recruited in the same rehabilitation clinics approximately 10 years apart. Methods The KAROLA cohorts included patients with CCS participating in an inpatient cardiac rehabilitation programme in Germany (KAROLA-I: 1999/2000, KAROLA-II: 2009-2011) [details in 4]. Blood samples and information on sociodemographic factors, lifestyle, and medical treatment were collected at baseline, at the end of rehabilitation, and after 1-year follow-up. A biomarker-based risk model (ABC-CHD model) [3] and Cox regression analysis were used to predict cardiovascular (CV) and non-CV mortality risk during 10 years of follow-up. Results We included 1130 patients from KAROLA-I (mean age 58.7 years, 84.4% men) and 860 from KAROLA-II (mean age 60.4 years, 83.4% men). Patients in the KAROLA-I cohort had significantly higher concentrations of CV biomarkers and fewer patients were taking CV medications, except for statins. The ABC-CHD model which also included age, current smoking, history of diabetes, peripheral arterial disease, as well as hs-cTNT, NT-proBNP, and LDL-cholesterol provided a higher estimate of CV death risk for patients in the KAROLA-I cohort (mean 3-year risk, 3.8%) than for patients in the KAROLA-II cohort (mean 3-year risk, 2.7%, p for difference &amp;lt;0.001). After 10 years of follow-up, 91 (8.1%) patients in KAROLA-I and 45 (5.2%) in KAROLA-II had died from a CV event. Non-CV mortality was quite similar among the two cohorts. Notably, when statin medication upon discharge was included as an exposure variable in the Cox model that included age, sex, biomarkers, and clinical variables for the combined analysis with both cohorts, the HR for CV mortality was 0.54 (95% CI 0.31-0.93) in patients taking high-potency statins compared with patients not on statin medication. Conclusions Advances in disease management including pharmacological treatment over the past 20 years may have led to modest improvement of long-term prognosis of patients with CCS.

NT-ProBNP and mortality across the spectrum of glucose tolerance in the general US population

BackgroundEven though hyperglycemia is a well-known cardiovascular risk factor, the absolute risk of cardiovascular events varies to a great extent within each glycemic category. The aim of this study is to evaluate whether N-terminal pro-B natriuretic peptide (NT-ProBNP) could help identify subjects at higher cardiovascular risk, independently of blood glucose levels.MethodsSerum NT-ProBNP levels were measured in 5502 people aged 45–79 years without heart failure from the general population (3380 with normoglycemia, 1125 with pre-diabetes and 997 with diabetes) that participated in the 1999–2004 cycles of the National Health and Nutrition Examination Survey. We applied Cox and Fine Gray models adjusted for cardiovascular risk factors to evaluate the association between NT-ProBNP levels and all-cause and cardiovascular mortality through December 2015.ResultsAfter a median follow-up of 13 years, 1509 participants died, 330 of cardiovascular causes. In the multivariable-adjusted models, compared with participants with NT-ProBNP < 100 pg/ml, those with levels 100–300 pg/ml and ≥ 300 pg/ml had a higher incidence of both all-cause mortality (HR 1.61, 95% CI 1.12–2.32, p = 0.012 and HR 2.96, 95% CI 1.75–5.00, p < 0.001, respectively) and cardiovascular mortality (HR 1.57, 95% CI 1.17–2.10, p = 0.011 and HR 2.08, 95% CI 1.47–2.93, p < 0.001, respectively). The association was consistent in subgroup analyses based on glycemic status, obesity, age and sex.ConclusionsElevated NT-ProBNP is independently associated with all-cause and cardiovascular mortality in the general population and could help identify patients at the highest risk. Further studies are needed to evaluate whether intensification of treatment based on biomarker data might lead to improvements in cardiovascular risk reduction.

Sodium nitroprusside in acute heart failure: A multicenter historic cohort study

AimsDespite evidence of hemodynamic benefit of sodium nitroprusside (SNP) treatment for acute heart failure (AHF), there are limited data about its efficacy and safety. This study aimed to assess the effectiveness and safety of SNP treatment, to explore the impact of N-terminal pro-B natriuretic peptide (NT-proBNP) reduction on clinical endpoints and to identify possible predictors of clinical response. Methods and resultsMulticenter retrospective cohort study of 200 patients consecutively admitted for AHF in 2 Italian Centers. Primary endpoint was the reduction of NT-proBNP levels ≥25% from baseline values within 48 h from the onset of SNP infusion. Secondary and safety endpoints included all-cause mortality, rehospitalization for HF at 1, 3 and 6 months, length of hospital stay (LOS) and severe hypotension. 131 (66%) patients experienced a NT-proBNP reduction ≥25% within 48 h from treatment onset, irrespective of initial systolic blood pressure (SBP). Left ventricular end diastolic diameter (LVEDD) was the only independent predictor of treatment efficacy. Patients who achieved the primary endpoint (i.e., ‘responders’) had lower LOS (median 15 [IQR:10–27] vs 19 [IQR:12–35] days, p-value = 0.033) and a lower incidence of all-cause mortality and rehospitalization for HF at 1 and 3 months compared to “non responders” (p-value <0.050). Severe hypotension was observed in 10 (5%) patients, without any adverse clinical consequence. ConclusionSNP is a safe and effective treatment of AHF, particularly in patients with dilated left ventricle. Reduced NT-proBNP levels in response to SNP is associated to shorter LOS and lower risk of 1- and 3-month re-hospitalizations for HF.Clinical trial registration.http://www.clinicaltrials.gov. Unique identifier: NCT05027360

Independent and joint association of N-terminal pro-B-type natriuretic peptide and left ventricular mass index with heart failure risk in elderly diabetic patients with right ventricular pacing.

BackgroundElevated levels of N-terminal pro-B natriuretic peptide (NT-proBNP) and left ventricular hypertrophy (LVH) are independent risk factors for heart failure (HF). In addition, right ventricular pacing (RVP) is an effective treatment strategy for bradyarrhythmia, but long-term RVP is associated with HF. However, there is limited evidence on the independent and combined association of NT-proBNP and left ventricular mass index (LVMI) with HF risk in elderly diabetic patients with long-term RVP.MethodsBetween January 2017 and January 2018, a total of 224 elderly diabetic patients with RVP at Fuwai Hospital were consecutively included in the study, with a 5-year follow-up period. The study endpoint was the first HF readmission during follow-up. This study aimed to explore the independent and joint relationship of NT-proBNP and LVMI with HF readmission in elderly diabetic patients with long-term RVP, using a multivariate Cox proportional hazards regression model.ResultsA total of 224 (11.56%) elderly diabetic patients with RVP were included in the study. During the 5-year follow-up period, a total of 46 (20.54%) patients suffered HF readmission events. Multivariate Cox proportional hazards regression analysis showed that higher levels of NT-proBNP and LVMI were independent risk factors for HF readmission [NT-proBNP: hazard risk (HR) = 1.05, 95% confidence interval (CI): 1.01–1.10; LVMI: HR = 1.14, 95% CI: 1.02–1.27]. The optimal cut-off point of NT-proBNP was determined to be 330 pg/ml by receiver operating characteristic (ROC) curve analysis. Patients with NT-proBNP > 330 pg/ml and LVH had a higher risk of HF readmission compared to those with NT-proBNP ≤ 330 pg/ml and non-LVH (39.02% vs. 6.17%; HR = 7.72, 95% CI: 1.34–9.31, P < 0.001).ConclusionIn elderly diabetic patients with long-term RVP, NT-proBNP and LVMI were associated with the risk of HF readmission. Elevated NT-proBNP combined with LVH resulted in a significantly higher risk of HF readmission.

Coronary microvascular dysfunction and findings of heart failure with preserved ejection fraction in patients with microvascular angina.

Coronary microvascular dysfunction (CMD) may cause symptoms of myocardial ischemia (microvascular angina [MVA]), but recent studies suggested that it might also contribute to the syndrome of heart failure with preserved ejection fraction (HFpEF). In this study we assessed the relation of CMD with findings of HFpEF in MVA patients. We enrolled 36 consecutive patients with MVA, in whom we assessed: 1) coronary blood flow (CBF) response to adenosine and cold pressor test (CPT) by color-Doppler echocardiography of the left anterior descending coronary artery; 2) complete echocardiographic examination; 3) N-terminal-pro-B-natriuretic peptide (NT-proBNP); 4) grade of dyspnea by the modified Medical Research Scale. Among patients, 15 had definite HFpEF findings (group 1), 12 had equivocal HFpEF findings (group 2) and 9 had no evidence of HFpEF findings (group 3). Group 1 patients were older, had more cardiovascular risk factors and higher NT-proBNP levels (P=0.018), and showed a higher prevalence of diastolic dysfunction. Left ventricle dimensions and systolic function, however, did not differ among groups. Dyspnea was also not significantly different among groups (P=0.19). CBF to adenosine was 1.85±0.47, 1.78±0.40 1.49±0.32 in group 1, 2 and 3, respectively (P=0.13). Similarly, CBF response to CPT was 1.57±0.4, 1.49±0.2 and 1.45±0.3 in the 3 groups, respectively (P=0.74). Both CBF response to adenosine and CPT showed no relation with the severity of dyspnea symptoms. Our data suggest that in patients with MVA there is no relation between the grade of impairment of coronary microvascular dilatation and findings of HFpEF.

Association between lipoprotein (a) and heart failure with reduced ejection fraction development.

BackgroundThe current study aimed to evaluate the relationship between baseline serum lipoprotein (a) [Lp(a)] level and heart failure with reduced ejection fraction (HFrEF) development.MethodsThis was a retrospective study, and participants were enrolled from the outpatient clinic. All data were extracted from the electronic health record of the outpatient clinic system. The follow‐up was performed through reviewing the clinical notes at the outpatient clinic system, and study outcome of the current study was the first diagnosis of HFrEF. Participants were divided into low Lp(a) (<30 mg/dl, n = 336) and high Lp(a) (≥30 mg/dl, n = 584) groups.ResultsIndividuals in the high Lp(a) group were more likely to be men and have diabetes mellitus (DM) and dyslipidemia. Increased Lp(a) at baseline was positively associated with serum N‐terminal pro‐B natriuretic peptide level while negatively associated with left ventricular ejection fraction (LVEF) at follow‐up. After adjusting for covariates, per 10 mg/dl increase in baseline Lp(a) remained significantly associated with HFrEF, with odds ratio of 1.17 (95% confidence interval of 1.05, 1.46). The magnitude of association between baseline Lp(a) level and HFrEF was greater in men and in individuals with DM or coronary heart disease (CHD), while it was weaker in individuals treated with beta‐blocker at baseline.ConclusionIncreased Lp(a) at baseline was associated with HFrEF development. The adverse effects of Lp(a) were greater on men and individuals with DM or CHD, which were mitigated by beta‐blocker therapy. These findings together underscore the possibility and usefulness of Lp(a) as a new risk factor to predict HFrEF.

Increase in Ischemia-Modified Albumin and Pregnancy-Associated Plasma Protein-A in COVID-19 Patients.

This study was undertaken due to the urgent need to explore reliable biomarkers for early SARS-CoV-2 infection. We performed a retrospective study analyzing the serum levels of the cardiovascular biomarkers IL-6, TNF-α, N-terminal pro-B natriuretic peptide, cardiac troponin T (cTnT), ischemia-modified albumin (IMA) and pregnancy-associated plasma protein-A (PAPP-A) in 84 patients with COVID-19.Patients were divided into three groups according to their RT-qPCR and IgG values: acute infection (n = 35), early infection (n = 25) or control subjects (n = 24). Levels of biomarkers were analyzed in patient serum samples using commercially available ELISA kits. Results showed a significant increase in IMA and PAPP-A levels in the early infected patients. Moreover, multivariate analysis and receiver operating characteristic (ROC) curve showed that IMA and PAPP-A had excellent discrimination value for the early stage of COVID-19. For IMA, the area under the ROC curve (AUC) had a value of 0.94 (95% confidence interval (CI): 0.881–0.999). Likewise, the serum level of PAPP-A was significantly higher in patients with early infection than in the control subjects (AUC = 0.801 (95% CI: 0.673–0.929)). The combined use of IMA and PAPP-A enhanced the sensitivity for total SARS-CoV-2-infected patients to 93%. These results suggest that the increased levels of PAPP-A and IMA shed light on underlying mechanisms of COVID-19 physiopathology and might be used as efficient biomarkers with high sensitivity and specificity for the early stage of COVID-19. Importantly, when monitoring pregnancy and cardiovascular diseases using PAPP-A or IMA levels, a SARS-CoV-2 infection should be discarded for proper interpretation of the results.

High Sensitivity Troponin T and NT-proBNP in Patients Receiving Chimeric Antigen Receptor (CAR) T-Cell Therapy

Retrospective studies suggest that chimeric antigen receptor T-cell (CAR T) therapy may lead to cardiac injury, but this has not been assessed systematically or prospectively. In this prospective study of 40 patients who received CAR T, we systematically measured high-sensitivity troponin T (hsTropT) and N-terminal pro-B natriuretic peptide (NTproBNP) at baseline and on day 1, days 7, and 21 after CAR T. Biomarker elevations with respect to timepoint and cytokine release syndrome (CRS) status were examined using repeated measure analysis of variance. hsTropT did not differ with time or with the presence of grade 2 CRS. Median hsTropT was 12.1 ng/L [interquartile range (IQR): 9.2, 20.1] at baseline, 13.1 ng/L (IQR: 9.6, 24.2) at day 1, 11.9 ng/L (IQR: 9.6, 18.0) at day 7, and 15.3 ng/L (10.8, 20.2) at day 21. In contrast, NTproBNP rose on day 1 (PWilcox = 0.0002) and day 7 (PWilcox = 2.7 × 10−5), and the degree of elevation differed by the presence of grade 2 CRS (Pinteraction = 0.002). Median NTproBNP was 179 pg/mL (IQR: 116, 325) at baseline, 357 pg/mL (IQR: 98, 813) at day 1, 420 pg/mL (IQR: 239, 1242) at day 7, and 177 pg/mL (IQR: 80, 278) at day 21. In conclusion, hsTropT l did not differ across timepoints after CAR T therapy, but NTproBNP rose at day 7, the prognostic implications of which should be the target of future research, as the indications for this therapy expand.

Subannular repair for functional mitral regurgitation type IIIb in patients with ischaemic versus dilated cardiomyopathy.

Functional mitral regurgitation (FMR) is a sequel of left ventricular (LV) remodelling in heart failure patients. Relocation of both papillary muscles aims to specifically address mitral leaflet tethering to improve long-term durability of modern FMR repair. Nevertheless, the prognostic impact of the underlying cardiomyopathy on the outcome after FMR repair is unknown. We analysed 84 consecutive heart failure patients with severe FMR, LV ejection fraction <40%, LV end-diastolic diameter ≥55 mm and tenting height >10 mm, who underwent ring annuloplasty and simultaneous bilateral papillary muscles relocation between June 2016 and March 2019. One-year outcome of 54 patients with ischaemic cardiomyopathy ('ICM group') was prospectively compared to the remaining 30 patients with dilated cardiomyopathy ('DCM group'). One-year survival was similar in both groups (96% in the 'ICM group' vs 97% in the 'DCM group'; P = 0.93). Furthermore, primary composite outcome (i.e. freedom from death or mitral regurgitation ≥ 2) at 1-year postoperatively was comparable between the study groups (94%in the 'ICM group' vs 87% in the 'DCM group'; P = 0.10). LV end-diastolic diameter 1-year after surgery was significantly reduced, as compared to preoperative values, in the 'DCM group' (P = 0.018), but not in the 'ICM group' (P = 0.058). Improvement of New York Heart Association functional class and reduction of serum levels of N-terminal pro-B natriuretic peptide at 1 year was comparable in both study groups. Standardized relocation of both papillary muscles to correct FMR resulted in very satisfactory in-hospital and 1-year outcomes, in both ICM and DCM. DCM patients showed similar improvement in heart failure symptoms and LV re-remodelling compared to ICM patients. Subannular repair is developing towards a valid therapeutic option in heart failure patients presenting with severe FMR.

NT-proBNP levels in preeclampsia, intrauterine growth restriction as well as in the prediction on an imminent delivery.

Studies of cardiovascular function in pregnancy have shown inconsistent and, in some cases, contradictory results, particularly regarding cardiac output. While some studies report preeclampsia associated with high cardiac output, other studies suggest that preeclampsia should be further subdivided into women with high or low cardiac output. This study was conducted to examine the NT-proBNP levels in preeclampsia, intrauterine growth restriction, and hypertensive pregnancies without preeclampsia. We also examined N-terminal pro-B natriuretic peptide (NT-proBNP) levels three to four months after delivery, in preeclamptic women as well as the prediction of delivery within 10days. In a reduced number of preeclamptic women and controls we performed echocardiograms to study their diastolic function. We investigated the NT-proBNP levels in 213 subjects with preeclampsia only, 73 with intrauterine growth restriction, 44 with preeclampsia and intrauterine growth restriction, 211 who were hypertensive and 662 unaffected pregnancies (controls). We also performed echocardiograms on 36 preeclampsia and 19 controls before delivery and three to five months after delivery. NT-proBNP levels are higher in early onset preeclampsia than in late onset preeclampsia. Intrauterine growth restriction pregnancies showed a NT-proBNP levels similar to hypertensive and unaffected pregnancies. Compared with healthy pregnancies, women with preterm preeclampsia (<37 gestational weeks) had altered left atrial segments. We observed that NT-proBNP levels are higher in early onset preeclampsia than in late onset. Moreover, diastolic dysfunction is higher in early onset than in late-onset term preeclampsia. An NT-proBNP value >136pg/mL has a high positive predictive value for an imminent delivery within 10days.

High-Sensitivity Cardiac Troponin, Natriuretic Peptide, and Long-Term Risk of Acute Kidney Injury: The Atherosclerosis Risk in Communities (ARIC) Study.

Cardiac markers such as high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B natriuretic peptide (NTproBNP) are predictors of developing acute kidney injury (AKI) during hospitalization for surgery or revascularization. However, their associations with the long-term risk of AKI in the general population are uncharacterized. We conducted a prospective cohort study in 10669 participants of the Atherosclerosis Risk in Communities Study (visit 4, 1996-1998, mean age, 63 years, 56% female, 22% black race) to examine the association of plasma concentrations of hs-cTnT and NTproBNP with the incident hospitalization with AKI. We used multivariable Cox regression analysis to estimate hazard ratios (HRs). During follow-up, 1907 participants had an incident hospitalization with AKI. Participants with higher concentrations of hs-cTnT had a higher risk of hospitalization with AKI in a graded fashion (adjusted HR, 1.88 [95%CI , 1.59-2.21] for ≥14 ng/L, 1.36 [1.18-1.57] for 9-13 ng/L, and 1.16 [1.03-1.30] for 5-8 ng/L compared to <5 ng/L). The graded association was also observed for NTproBNP (HR, 2.27 [1.93-2.68] for ≥272.7 pg/mL, 1.67 [1.45-1.93] for 142.4-272.6 pg/mL, and 1.31 [1.17-1.47] for 64.0-142.3 pg/mL compared to <64.0 pg/mL). The addition of hs-cTnT and NTproBNP to a model with established predictors significantly improved 10-year risk prediction for hospitalization with AKI (Δc-statistic, 0.015 [95%CI, 0.006-0.024]). In middle-aged to older black and white adults in the community, higher concentrations of hs-cTnT and NTproBNP were robustly associated with an increased risk of hospitalization with AKI. These results suggest the usefulness of hs-cTnT and NT-proBNP to identify people at risk of AKI in the general population.

Endocrine and Mechanical Cardiacfunction Four Months after Radiofrequency Ablation of Atrialfibrillation.

Radiofrequency ablation (RFA)is an important treatment option for patients with atrial fibrillation (AF). During RFA, a significant amount of energy is delivered into the left atrium (LA), resulting in considerable LA-injury. The impact of this damage on mechanical and endocrine LA-function, however, is often disregarded.We therefore aimed to evaluate the endocrine- and mechanical function of the heart 4-months after RFA of AF. In total 189 patients eligible for RFA of AF were studied. The levels of the N-terminal pro-B-natriuretic peptide (NT-proBNP) and the mid-regional fragment of the N-terminal pro-atrial natriuretic peptide (MR-proANP)were measured. The maximum LAvolume (LAVmax),the LAejection fraction (LAEF) and the LA peak longitudinal strain (PALS), were measured usingtransthoracic echocardiography. The measurements were performed before and 4-months after the intervention. 87 patients had a recurrence during a mean follow-up of 143±36 days.NT-proBNPand MR-proANPdecreased significantly at follow-up. This reduction was greater in patients who did not suffer any recurrence after RFA.The LAVmax decreased significantly, whereasthe PALS only improved in patients who did not suffer from any recurrence. On the other hand, LAEF did not change significantly after RFA of AF. Despite extensiveablation during RFA of AF, the endocrine function of the heart improved 4-months after the index procedure. Patients with no arrhythmia recurrence showed a more pronounced improvement in their endocrinal function. Mechanically, the LAVmax was reduced, and the LA strain improved significantly.

Speckle tracking echocardiography for the evaluation of left ventricular function in children with systemic lupus erythematosus.

Many studies in adult patients with systemic lupus erythematosus (SLE) have demonstrated that myocardial dysfunction was significantly associated with enhanced disease activity. However, similar studies in paediatric patients with SLE are limited. The aim of this study was to evaluate the role of speckle tracking echocardiography (STE) to detect left ventricular dysfunction in children with active and inactive SLE. This prospective case-control study was carried out on 50 children with SLE. Thirty healthy age- and sex-matched children comprised the control group. The patients were further subdivided into two subgroups: active SLE and inactive SLE. Laboratory investigations undertaken included complete blood count, renal function, C3, C4, ANA, anti-dsDNA and serum N-terminal pro-B type natriuretic peptide. Echocardiographic examinations were performed on all children and included conventional echocardiography, tissue Doppler imaging (TDI) and two- and three-dimensional STE. There was no statistically significant difference in N-terminal pro B natriuretic peptide between the studied groups. The myocardial performance index by TDI was statistically significantly higher in SLE patients compared to controls. STE parameters were statistically significantly lower in SLE patients compared to controls. There was no correlation between STE parameters and disease activity. STE could be a promising technique in the early detection of subclinical left ventricular dysfunction in children with SLE.

Cardiac Biomarkers and Subsequent Risk of Hospitalization With Bleeding in the Community: Atherosclerosis Risk in Communities Study.

Backgroundhs‐cTnT (high‐sensitivity cardiac troponin T), but not NT‐proBNP (N‐terminal pro–B natriuretic peptide), has been shown to predict bleeding in patients with atrial fibrillation. Whether these biomarkers are independently associated with bleeding in the general population is unknown.Methods and ResultsWe used Cox proportional hazards models to examine the association of hs‐cTnT and NT‐proBNP with incident bleeding (defined by International Classification of Diseases, Ninth Revision [ICD‐9] codes) among 9550 middle‐aged men and women without a history of cardiovascular disease or bleeding. There were 847 hospitalizations with bleeding (92% from gastrointestinal bleeding) during a median follow‐up of 9.0 years. Serum levels of hs‐cTnT were associated with bleeding in a graded fashion, with a hazard ratio of 1.28 (95% CI, 1.06–1.59) for 6 to <9 ng/L, 1.52 (1.21–1.91) for 9 to <14, and 2.05 (1.56–2.69) for ≥14 versus <3 ng/L. For NT‐proBNP, the highest category (≥264 versus <42 pg/mL) showed a hazard ratio of 2.00 (1.59–2.61), and the remaining 3 categories had hazard ratios ranging from 1.2 to 1.3. Individuals in the highest category of both hs‐cTnT and NT‐proBNP had a hazard ratio of 3.03 (1.97–4.68) compared with those in the lowest categories.ConclusionsIn a community‐based population, elevated hs‐cTnT and NT‐proBNP were associated with bleeding‐related hospitalizations. These biomarkers may have a high utility in identifying people at high risk for bleeding. There is a need for research on the underlying mechanisms linking subclinical cardiac abnormalities and bleeding.

Representativeness of the PIONEER-HF Clinical Trial Population in Patients Hospitalized with Heart Failure

Introduction In the PIONEER-HF trial, the in-hospital initiation of sacubitril/valsartan in patients hospitalized for acute decompensated heart failure (ADHF) was well-tolerated and led to a greater reduction in N-terminal pro-B natriuretic peptide compared with enalapril, and reduced HF hospitalizations. In this study, we aimed to: (1) determine eligibility for the PIONEER-HF trial among patients in a contemporary registry population with ADHF and HF with reduced ejection fraction (”all HFrEF”), (2) determine eligibility for sacubitril/valsartan using criteria most relevant to daily clinical practice (“actionable” cohort), and (3) compare long-term outcomes between the all HFrEF, PIONEER-HF trial eligible, and actionable cohorts using linked Medicare claims data. Methods The initial study population was derived from all patients discharged alive in the Get With The Guidelines-HF(GWTG-HF) registry between January 2006 and June 2018 with a left ventricular ejection fraction ≤40%. We derived cohorts meeting PIONEER-HF trial eligibility criteria and a set of clinically relevant criteria. Rates of HF-readmissions and all-cause mortality 1-year post index discharge were obtained linking the GWTG-HF registry with Medicare fee-for-service claims. Results Total of 99,767 patients in GWTG-HF were hospitalized for ADHF and HFrEF. PIONEER-HF inclusion criteria were met by 71,633 (71.8%) patients, and both inclusion and exclusion criteria were met by 20,704 (20.8%). 68,739 (68.9%) patients met the criteria for the actionable cohort (Figure). Among the CMS-linked patients, the 1-year all-cause mortality was 36.7% for all HFrEF patients, 32.2% for the actionable cohort and 31.6% for the PIONEER-HF trial eligible cohort (Log rank test P Conclusions Patient characteristics and clinical outcomes in participants enrolled in PIONEER-HF only modestly differ compared with those encountered in routine practice, suggesting the findings of this trial may be broadly generalizable.

Assessment of clinical effect and treatment quality of immediate-release carvedilol-IR versus SLOW release carvedilol-SR in Heart Failure patients (SLOW-HF): study protocol for a randomized controlled trial

BackgroundCarvedilol is a non-selective, third-generation beta-blocker and is one of the cornerstones for treatment for patients with heart failure and reduced ejection fraction (HFrEF). However, due to its short half-life, immediate-release carvedilol (IR) needs to be prescribed twice a day. Recently, slow-release carvedilol (SR) has been developed. The aim of this study is to evaluate whether carvedilol-SR is non-inferior to standard carvedilol-IR in terms of its clinical efficacy in patients with HFrEF.Methods/designPatients with stable HFrEF will be randomly assigned in a 1:1 ratio to the carvedilol-SR group (160 patients) and the carvedilol-IR group (160 patients). Patients aged ≥ 20 years, with a left ventricular ejection fraction ≤ 40%, N-terminal pro B-natriuretic peptide (NT-proBNP) ≥ 125 pg/ml or BNP ≥ 35 pg/ml, who are clinically stable and have no evidence of congestion or volume retention, will be eligible. After randomization, patients will be followed up for 6 months. The primary endpoint is the change in NT-proBNP level from baseline to the study end. The secondary endpoints include the proportion of patients with NT-proBNP increment > 10% from baseline, composite of all-cause mortality and readmission, mortality rate, readmission rate, changes in blood pressure, quality of life, and drug compliance.DiscussionsThe SLOW-HF trial is a prospective, randomized, open-label, phase-IV, multicenter study to evaluate the therapeutic efficacy of carvedilol-SR compared to carvedilol-IR in HFrEF patients. If carvedilol-SR proves to be non-inferior to carvedilol-IR, a once-daily prescription of carvedilol may be recommended for patients with HFrEF.Trial registrationClinicalTrials.gov, ID: NCT03209180. Registered on 6 July 2017.

Effects of long-term iloprost treatment on right ventricular function in patients with Eisenmenger syndrome

BackgroundRight ventricular (RV) function is an important prognostic factor of pulmonary arterial hypertension (PAH), but there is insufficient data regarding RV function after long-term inhaled iloprost treatment. We evaluated the effect of long-term iloprost treatment on RV function in patients with Eisenmenger syndrome (ES). MethodsEleven consecutive patients with ES associated with congenital heart disease underwent echocardiographic measurements at baseline and 48 weeks after iloprost therapy. In addition, we recorded World Health Organization (WHO) functional class, 6-minute walk distance (6MWD), systemic arterial oxygen saturation (SaO2), and laboratory values such as hemoglobin, serum creatinine, and N-terminal pro-B natriuretic peptide. ResultsAfter 48 weeks of iloprost therapy, mean pulmonary arterial pressure (mPAP), pulmonary arterial systolic pressure (PASP), and pulmonary vascular resistance (PVR) were significantly decreased [mPAP, 42.5 (38.5–61.0) to 36.5 (29.1–40.0)mmHg; PASP, 92.6±19.9 to 74.5±23.8mmHg; PVR, 23.4 (19.8–26.0) to 23.4 (19.8–26.0)Wood unit respectively, all p<0.05]. There was also significant improvement in RV myocardial performance index [0.68 (0.61–0.80) to 0.52 (0.51–0.62), p=0.003] and RV longitudinal strain (−15.7±1.6 to −18.1±1.5%, p<0.001). In clinical assessment, WHO functional class (p=0.006), 6MWD (310.6±44.7 to 399.7±80.8m, p<0.001), and SaO2 (90.9±6.0% to 92.5±6.0%, p=0.022) were significantly improved. ConclusionThe improvement in echocardiographic parameters of the RV function after 48 weeks of iloprost therapy may provide insight on the efficacy of long-term iloprost treatment for RV functional improvement, which is a prognostic factor in patients with ES.

Diagnostic performance and reference values of novel biomarkers of paediatric heart failure

ObjectiveBiomarkers play a pivotal role in heart failure (HF) management. Reference values and insights from studies in adults cannot be extrapolated to the paediatric population due to important differences in...