NT-proBNP Research Articles

Is pulmonary vascular remodeling an intermediate link between hyperglycemia and adverse outcomes in patients with idiopathic pulmonary arterial hypertension? Insights from a multi-center cohort study

BackgroundHyperglycemia upon admission is associated with poor prognosis of many cardiovascular diseases. However, the relationship of stress hyperglycemia ratio (SHR), admission blood glucose (ABG), and hemoglobin A1c (HbA1c) with pulmonary hypertension has not been reported. This study aimed to explore the association of hyperglycemia indices with disease severity and long-term adverse outcomes in patients with idiopathic pulmonary arterial hypertension (IPAH).MethodsThis multi-center cohort study included 625 consecutive patients diagnosed with or treated for IPAH between January 2015 and June 2023. SHR was calculated using the followings: ABG (mmol/L)/(1.59 × HbA1c [%] − 2.59). The primary endpoint was defined as clinical worsening events. Multivariable Cox regression and restricted cubic spline analyses were employed to evaluate the association of SHR, ABG, and HbA1c with endpoint events. The mediating effect of pulmonary hemodynamics was evaluated to investigate the potential mechanism between hyperglycemia and clinical outcomes.ResultsDuring a mean follow-up period of 3.8 years, 219 (35.0%) patients experienced all-cause death or clinical worsening events. Hyperglycemia indices correlated with well-validated variables that reflected the severity of IPAH, such as the World Health Organization functional class, 6-min walk distance, and N-terminal pro-brain natriuretic peptide levels. Multivariable Cox regression analyses indicated that SHR (hazard ratio [HR] 1.328, 95% confidence intervals [CI]: 1.185, 1.489 per 0.1-unit increment, P < 0.001) and ABG (HR 1.317, 95% CI: 1.134, 1.529 per 1.0-unit increment, P < 0.001) were independent predictors of primary endpoint events. Mediation analysis indicated that pulmonary vascular resistance mediated 5.65% and 14.62% of the associations between SHR and ABG and clinical worsening events, respectively. The addition of SHR significantly improved reclassification, discrimination ability, and model fit beyond the clinical risk prediction model.ConclusionsSHR is positively associated with clinical worsening in patients with IPAH. The association appeared to be partially mediated through the pathway of pulmonary vascular remodeling, indicating that SHR may serve as a valuable indicator for providing additional risk information.

The dynamics of urine sodium concentration after intra-venous furosemide in patients with acute heart failure

Abstract Background The urine sodium concentration measured at 2 hours after the administration of intravenous (IV) furosemide in patients with acute heart failure (AHF) is recommended as a marker to assess the responsiveness to IV furosemide. However, little is known regarding the dynamics of natriuresis in the very acute phase after IV furosemide and its association with prognosis in patients with AHF. Purpose The aim of this study is to investigate the dynamics of natriuresis in the very acute phase after IV furosemide and its prognostic implication in patients with AHF. Methods DIURESIS-AHF (Diuretic Resistance Measured by Sodium Excretion and Urine Output in Acute Heart Failure) is a multicenter, prospective, and observational study that evaluated the urine samples at the time of 0h, 1h, 2h, 6h, and 24h after the first administration of IV furosemide in hospitalized patients with AHF. Results After excluding 20 patients who needed additional IV furosemide within the first 6 hours, and 9 patients with missing data about 1h-spot urine sample, 84 patients with AHF (79±8 years, 55% men) were analyzed. Median N-terminal pro-brain natriuretic peptide levels at admission were 4722 [interquartile: 2616-8095] pg/mL, and median first IV furosemide doses were 20 [interquartile:20-20] mg. 29 combined event of all-cause death and heart failure rehospitalization were observed during a 1-year follow-up after registration. Urine sodium concentration corrected for urine creatinine concentration peaked 1 hour and decreased at 2 hours after IV furosemide. Kaplan-Meier curve analysis indicated that 1h urine sodium concentration below 50 mEq/L was significantly associated with a high incidence of composite endpoint (Log-rank P=0.033), and this association was retained even after adjusting for age and sex (hazard ratio, 2.37 [95% CI, 1.03-5.45]; P=0.042), but 2h urine sodium below 50 mEq/L was not associated with a poor prognosis (Log-rank; P=0.630). Conclusions Urinary sodium excretion after IV furosemide administration peaked at 1 hour after IV furosemide and decreased at 2 hours in patients with AHF. The urine sodium concentration below 50 mEq/L at 1 hour, but not 2 hours, was associated with adverse events.Urine Na trajectoriesKaplan Meier curves

Metoprolol therapy in patients with Eisenmenger syndrome (MINES) study. A single-centre, double-blinded, randomised, placebo-controlled trial

Abstract Background Prevalence of Eisenmenger syndrome is still common in developing countries where early neonatal screening and referral for surgery is seldom possible. Limited number of drugs are available for treatment of this condition. Beta-blockers may improve functional status in these patients. Observational study has shown beta blockers to be safe and effective in improving effort intolerance in patients with Eisenmenger syndrome. Purpose To study the safety and efficacy of metoprolol succinate therapy in patients with Eisenmenger syndrome. Methods In this double-blind, placebo-controlled study, we randomly assigned 60 patients with Eisenmenger syndrome to receive placebo or to receive 25 mg of metoprolol succinate once daily for 2 weeks followed by 25 mg twice daily for 14 weeks (total of 16 weeks). The primary outcome was mean difference in 6-minute walk test (6MWT) distance. Secondary outcomes were clinical composite outcome (all-cause death, heart failure hospitalization, worsening of heart failure, change in WHO functional class, and new onset syncope), change in resting saturation, Tricuspid Annular Plane Systolic Excursion (TAPSE) and NT Pro BNP level at 16 weeks. Results At 16 weeks, the mean difference in 6MWT distance between treatment group and placebo group as per protocol analysis was 6 meters (95% confidence interval, - 7.43 to 19.49; P 0.37), and the mean difference in 6MWT distance as per intention to treat analysis was -1.1 meters (95% confidence interval, - 16.97 to 14.77; P 0.89). Clinical composite outcome occurred more in the treatment group 5(17%) as compared to the placebo group 1(3%) (P 0.197) though it did not reach statistical significance. This was primarily driven by worsening of heart failure in the treatment group. Compared to baseline metoprolol group had 37% increase in NT pro BNP level while placebo group had 13% (-313.69, 88.80) reduction in NT Pro BNP level. There was no difference in TAPSE 0.05 (95% confidence interval -0.62 to 0.72; P 0.88) or resting saturation -0.06 (95% confidence interval -0.88 to 0.75; P 0.87) between the two groups at 16 weeks Conclusion Metoprolol succinate therapy did not improve 6-minute walk distance at 16 weeks among patients with Eisenmenger syndrome compared to placebo. Metoprolol succinate therapy was associated with increased clinical composite outcomes, primarily driven by worsening of heart failure.Graphic Abstract of MINES study

5-year valve academic research consortium-3 outcomes and predictors of mortality in a 10-year Asian transcatheter aortic valve implantation registry

Abstract Background Transaortic valvular implantation (TAVI) has revolutionised the management of aortic stenosis (AS). Uptake in Asia has caught up in recent years, after an initial lag due to expensive cost, limited subsidies, and scarce accessibility. Hence, longitudinal outcomes of TAVI remain largely unknown in Asian patients. Purpose This study aims to present the 5-year mortality endpoints in an Asian cohort followed up over a decade. Methods 253 patients with symptomatic severe aortic stenosis status post TAVI were retrospectively enrolled at a tertiary academic hospital from 2010-2021. The main outcomes were defined as short-term (30-day), mid-term (1-year) and long-term (5-year) all-cause mortality. Baseline demographics, procedural findings and clinical outcomes were analysed. Kaplan-Meier curves and multiple Cox regression analyses were constructed. Results The mean age was 75.2 + 10.2 years. 120 (47.4%) patients were female and 167 (66%) were Chinese. 168 patients (66.7%) received balloon-expandable valves, 80 patients (31.7%) underwent self-expandable valves, and 4 patients (1.6%) had mechanical-expandable valves. Malignancy was associated with worse short-term mortality at 30-days (HR 3.65, p = 0.054), while pulmonary disease and previous stroke were associated with worse long-term mortality at 5-years (HR 2.27, p = 0.012 and HR 2.02, p = 0.064). Worse all-cause mortality at 30-days, 1-year and 5-years were associated with high NT-Pro BNP levels (HR 1.04, p = 0.046; HR 1.05, p = 0.002 and HR 1.04, p &amp;lt; 0.001), the presence of peripheral arterial disease (PAD) (HR 4.32, p = 0.056; HR 4.48, p = 0.006 and HR 2.43, p = 0.023) and chronic kidney disease (CKD) (HR 6.19, p = 0.006; HR 6.77, p &amp;lt; 0.001 and HR 2.09, p = 0.008). Society of Thoracic Surgery (STS) score (HR 1.11, p = 0.001; HR 1.13, p &amp;lt; 0.001 and HR 1.12, p &amp;lt; 0.001) and Valve Academic Research Consortium (VARC) III endpoints of acute kidney injury (AKI) (HR 6.68, p = 0.047, HR 10.8, p &amp;lt; 0.001 and HR 6.99, p &amp;lt; 0.001), cardiogenic shock (HR 26.3, p &amp;lt; 0.001, HR 12.0, p &amp;lt; 0.001 and HR 4.29, p = 0.011) and structural complications (HR 40.3, p &amp;lt; 0.001, HR 18.1, p &amp;lt; 0.001 and HR 5.18, p = 0.008) were associated with worse all –cause mortality at time-points of 30-days, 1-year and 5-years respectively. On multivariate analyses adjusted for comorbidities and outcomes, STS score and structural complications were independent predictors of 30-day, 1-year, and 5-year all-cause mortality (HR 1.16; p = 0.003, HR 1.09, p = 0.003 and HR 1.10, p &amp;lt; 0.001) and (HR 62.7, p &amp;lt; 0.007; HR 18.9, p &amp;lt; 0.001 and HR 10.6, p = 0.001) respectively. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) use was protective of survival within 1-year (HR 0.37, p = 0.022). Conclusions STS score and VARC III endpoints of structural complications were reliable predictors of all-cause mortality in Asian patients with TAVI. ACE inhibitor and ARB use was protective against mortality at 1-year.Cox regression analysesKaplan-Meier curves

The impact of exogenous ketone body suppletion on energy and pH balance in skeletal muscle during exercise in chronic heart failure patients: a prospective randomized double-blind cross-over study

Abstract Background Heart Failure (HF) is characterized by impediments in exercise capacity. Disruptions in the energy metabolism of skeletal muscle contribute to this condition. Pre-clinical and clinical evidence showed that reductions in carbohydrate and FA metabolism in HF may be partially overcome by a compensatory increase in ketone body oxidation and suggest that suppletion of ketone bodies (KB) may improve energy metabolism in HF. Purpose We tested the effect of exogenous KB suppletion on energy and pH balance during cycling exercise using 31P Magnetic Resonance (MR) Spectroscopy of the exercising quadriceps muscle in patients with HF. Methods In a randomized, double-blind, placebo-controlled cross-over study, 14 stable HF patients with reduced ejection fraction and diminished exercise capacity underwent maximal exercise testing in a MR scanner fitted with a cycling ergometer after KB or placebo treatment. Phosphocreatine (PCr) and inorganic phosphate (Pi) resonance amplitudes and frequencies were measured continuously in the quadriceps muscle during rest, exercise and recovery using in-vivo 31P MR spectroscopy (Figure 1). Results Patients had a median age of 66 [53 – 75] years, were 14% female, had a median LVEF of 37% [27 – 40] and circulating NT-pro BNP levels of 411 [182 – 946] pg/mL. Peak oxygen uptake (VO2) was 18.2 [15.2 – 20.3] ml/kg/min, which is 68% [62 – 78%] of predicted. After treatment, exercise performance in terms of cycling duration and workload were comparable between treatment arms (Figure 2). Quadriceps acidification during exercise was larger after KB suppletion compared to placebo (ΔpH: -0.2 [-0.3 - -0.1] vs -0.1 [-0.3 - -0.1] respectively; p=0.041) while quadriceps energy depletion during exercise was not altered by treatment (ΔPi/PCr 0.77 [0.55 – 2.51] vs 0.66 [0.46 – 0.81] respectively; p=0.087). Post-exercise mitochondrial oxidative function was similar between treatment arms (KB: PCr resynthesis rate 48 sec [25 – 59] versus placebo: 42 sec [36 – 63]; p=0.767). Conclusions Ketone body suppletion increased acidification and did not improve energy balance in skeletal muscle during exercise or mitochondrial function during recovery in patients with chronic HF. These results question the value of ketone bodies as treatment to boost muscular energy metabolism during exercise in HF.31P MRS Spectrum during exercise in HFExercise and energy parameters

Comparison of pulsed field ablation versus cryoballon and radiofrequency ablation for pulmonary vein isolation in atrial fibrillation patients with heart failure

Abstract Background Pulmonary vein isolation (PVI) is the gold standard for atrial fibrillation (AF) ablation and can be achieved by a variety of technical methodes. While thermal ablation modalities (TA), such as cryoballon (CB) and radiofrequency ablation (RF) have been established as the standard approaches, PFA has been introduced as a nvel non-thermal modality showing comparable safety and procedural efficiency. Despite the high incidence of AF in heart failure (HF) patients, data comparing outcomes of HF patients undergoing PVI by either PFA or thermal ablation (RFA/CB) are limited. Purpose This study’s aim was to compare the efficacy and safety of PFA for AF ablation versus CB/RFA in HF patients. Methods Consecutive HF patients with preserved (HFpEF), mildly reduced (HFmrEF) and reduced (HFrEF) ejection fraction undergoing PVI for AF by either PFA or CB/RFA at our institution were included. The primary end-point was time to death or recurrence of AF. Secondary end-points were periprocedural complications and clinical and echocardiographic parameters. Results We included 140 HF patients who underwent PVI either by PFA (PFA group, 76 patients) or thermal ablation approaches (TA group, 64 patients). Our patients had a mean age of 69 years and were predominantly male (62%). There was no significant difference in the baseline characteristics and in the type of AF between both groups (42% with ParAF, 45% with PersAF) and 13% LSPersAF). The distribution of heart failure types was similar between both groups: HFpEF (PFA: 71%, TA: 75%), HFmrEF (PFA: 21%, TA: 20%) and HFrEF (PFA: 8 %, TA: 5%). After the 365-days follow-up period we observed no significant difference for the primary end-point between both groups (HR: 0.79, 95% CI 0.35-1.78; p=0.575). In total 58% of the PFA patients and 59% of the TA group were still free from AF. While symptom improvement was documented in both groups, patients in the PFA group showed significant improvement of left atrial volume index (p = 0.014), NT-pro BNP levels (p = 0.046), and left ventricular ejection fraction (LVEF) (p = 0.005). Conclusion In this study, PFA and thermal ablation modalities showed comparable results in terms of safety and procedural efficiency in patients with heart failure. Since previous studies have shown that HF patients with AF benefit from PVI using thermal ablation modalities, our results suggest that PFA might also be a promising ablation method in this vulnerable population, inducing left atrial reverse remodeling and thereby contributing to improvement of left ventricular systolic function.

Latent cytomegalovirus infection associates with impairments in myocardial reperfusion, left-ventricular function, and quality of life after ST-elevation myocardial infarction

Abstract Introduction Cytomegalovirus (CMV) is a ubiquitous herpesvirus affecting the majority of adults in European countries. CMV influences T-lymphocyte biology throughout life. We have previously associated CMV status with adverse left ventricular (LV) remodeling after ST-elevation myocardial infarction (STEMI) in a single-centre study. In this study, we aimed to assess the external validity of these findings. Methods This study is a retrospective analysis of 354 patients presenting with STEMI, who were recruited to A Trial of Low-Dose Adjunctive Alteplase During Primary PCI (T-TIME) and had blood samples archived. The participants underwent immediate coronary angiography and percutaneous coronary intervention (PCI), serial cardiovascular magnetic resonance (CMR) imaging at 2-7 days and 3 months post-STEMI, and serial assessment of health-related quality of life with the standardised EQ-5D visual analogue scale (VAS). CMV IgG titre was measured in cryopreserved samples from each patient, and patients were categorised as CMV negative, low-positive or high-positive. All analyses were adjusted for infarct location. Results Of 354 patients, 175 (49.4%) were CMV IgG titre negative, 89 (25.1%) were low-positive and 90 (25.4%) were high-positive. CMV+ patients were older (62.5 vs 58.7 years) and more likely to be non-White (6.7% vs 2.3%). CMV+ patients displayed several adverse outcomes. First, myocardial reperfusion was impaired. Thrombolysis in myocardial infarction (TIMI) flow grade 3 after PCI, indicating complete reperfusion, was less common in CMV+ patients (76.0% vs 84.6%; p=0.042). CMV+ patients also had a higher TIMI frame count after PCI (p=0.021), and non-significantly less ST-segment resolution at 60 minutes (38.8% vs 48.4%; p=0.066). Impaired myocardial reperfusion appeared to lead to impaired LV function, with LV ejection fraction (LVEF) measured on early CMR lower in CMV+ patients (42.6% vs 45.3%, p=0.004). At 3 months, LV function remained impaired in CMV+ patients (LVEF: 47.8% vs 49.7%; p=0.035). This was mirrored by CMV+ patients displaying higher NT-pro BNP levels at 2-7 days (1381 vs 1172pg/mL, p=0.097) and 3 months (575 vs 338pg/mL, p=0.021). Finally, impaired LV function appeared to affect quality of life. Over 3 months, in contrast to CMV-negative patients, those with the highest CMV IgG experienced almost no improvement in quality of life, measured by change in the EQ-5D VAS (negative: +9.93; high-positive: +0.70; p=0.0002). Conclusion CMV+ patients with STEMI experience worse outcomes, with impaired reperfusion, persistently reduced LV function and less improvement in health-related quality of life over 3 months. We hypothesise that the effect of CMV is mediated through immune activation. Future research should explore the mechanisms by which CMV-specific lymphocytes interact with myocardial reperfusion and repair post-STEMI.

Left atrial reservoir strain as a prognostic indicator for cardiovascular events after mitral valvuloplasty

Abstract Background In patients after mitral valvuloplasty (MVP), assessing valve function and heart failure (HF) is crucial for prognostic predictions. Left ventricular diastolic function assessed by transthoracic echocardiography (TTE) plays an important role in the evaluation of HF in general practice. However, post-mitral valve surgery patients are excluded from the left ventricular diastolic function assessment guidelines proposed by the American Society of Echocardiography in 2016 due to their low correlation with left ventricular diastolic function indices. On the contrary, the left atrial reservoir strain (LARS) before MVP is considered as a prognostic factor, reflecting left atrial dysfunction caused by mitral regurgitation. Nevertheless, there are limited reports on the relationship between LARS and cardiovascular (CV) events after MVP. Purpose The study aims to investigate the utility of LARS in predicting CV events after MVP. Methods The study included 249 patients who underwent TTE between January 2011 and January 2023 after MVP at our hospital. Patient background data, including NYHA classification, medical history, medications, blood tests, and TTE data, were collected at the time of follow-up TTE. LARS, left ventricular global longitudinal strain (LV-GLS), and right ventricular free wall strain (RV-FWSL) analysis were performed using a vender-independent external strain analysis software for all patients in the cohort. The primary endpoints were cardiovascular death and HF rehospitalization. The predictor of cardiovascular events was assessed using the Cox proportional hazards model and Kaplan-Meier curve (KMC). Results The mean age was 61±14 years, and 159 patients (64%) were male. The median time from surgery to TTE was 4.8 (1.0-6.8) years, 32 patients (13%) had events within 8.5 (3.7-10.8) years after TTE. The event groups had higher age, NYHA classification, and NT-pro BNP compared to the non-event group. TTE parameters such as left ventricular mass index, left ventricular end-diastolic volume and end-systolic volume were larger, and LV-GLS and LARS were significantly lower in the event group. In multivariate Cox proportional hazards models showed that LARS was also a prognostic indicator even after adjustment for several variables (Table 1). The KMC showed that LARS was associated with events regardless of left atrial volume index (Log-rank p &amp;lt;0.001, chi-square:31.03) (Figure 1). Conclusion LARS was strongly associated with CV events after MVP. We consider LARS to be a useful prognostic indicator after MVP.

Diagnostic accuracy of NT-proBNP to predict the incidence of CSA-AKI: A systematic review and meta-analysis.

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a severe complication following cardiac surgery. Early identification and diagnosis are critical. In this study, we aim to systematically assess the diagnostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for CSA-AKI. The PubMed, Embase, Web of Science, and Cochrane Library databases were searched from January 1971 to October 2023 to identify prospective observational and retrospective observational studies. Data extraction and study screening were carried out independently by 2 authors. The methodological quality of the included studies was evaluated by the Quality Assessment of Diagnostic Accuracy Studies 2 standards, and all statistical analyses were conducted by Stata 15.0. Seven studies including 37,200 patients were identified. The pooled sensitivity of 0.67 (95% credible interval [CI] = 0.56-0.77), specificity of 0.55 (95% CI = 0.45-0.64), area under the summary receiver operating characteristic curve of 0.65 (95% CI = 0.60-0.69), positive likelihood ratio of 1.5 (95% CI = 1.2-1.8), negative likelihood ratio of 0.60 (95% CI = 0.46-0.79), and diagnostic odds ratio of 2 (95% CI = 2-4) suggested that patients with higher preoperative NT-proBNP levels (pg/mL) are at higher risk of developing acute kidney injury after cardiac surgery. However, NT-proBNP lacks sufficient sensitivity and specificity to reliably predict CSA-AKI. Our findings suggest that the diagnostic accuracy of NT-proBNP to predict the incidence of CSA-AKI is limited. However, we provide novel perspectives on the early detection of CSA-AKI biomarkers, and it is urgent to identify more precise and practical biomarkers for the early diagnosis of CSA-AKI.

Association Between Derivatives of Reactive Oxygen Metabolites and Hemodynamics in Children with Left-to-Right Shunt Congenital Heart Disease

Existing reports on the association between oxidative stress and pulmonary hemodynamics in congenital heart disease (CHD) are limited, and the relationship remains inadequately understood. To address this, we evaluated the link between oxidative stress and hemodynamics in children with left-to-right shunt CHD. We analyzed the derivatives of reactive oxygen metabolites (d-ROMs) in a cohort of 60 children with left-to-right shunt CHD and compared them to 60 healthy, age- and sex-matched controls. In the CHD group, hemodynamics measured by cardiac catheterization were evaluated in relation to d-ROMs. We also assessed the diagnostic performance of the d-ROMs for a pulmonary-to-systemic blood flow ratio (Qp/Qs) of &gt;1.5. We found that the blood d-ROM levels in the CHD group were significantly higher than those in the control group (p &lt; 0.001). A significant positive correlation was observed between d-ROMs and Qp/Qs (p &lt; 0.001), d-ROMs and the ratio of the right ventricular end-diastolic volume (p &lt; 0.001), d-ROMs and the mean pulmonary arterial pressure (p &lt; 0.001), and d-ROMs and the ratio of the left ventricular end-diastolic volume (p = 0.007). In the receiver operating characteristic curve analysis, the area under the curve for d-ROMs in predicting Qp/Qs &gt; 1.5 was 0.806 (p &lt; 0.001), which, although not statistically significant, was higher than that of the plasma N-terminal pro-brain natriuretic peptide (0.716). These findings indicate that d-ROM levels are closely associated with hemodynamics and the disease severity in patients with left-to-right shunt CHD and may serve as a valuable marker for determining the need for surgical intervention.

Analysis factors influencing left ventricular thrombus in patients with non-ischemic heart failure

Objective: To explore the influencing factors of left ventricular thrombus (LVT) in patients with non-ischemic heart failure (NIHF) and to construct a nomogram prediction model for NIHF patients with LVT. Methods: This study was a case-control study. A total of 2 592 patients with NIHF hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from January 2018 to July 2022 were selected. Fifty-one patients with LVT identified by echocardiography and cardiac magnetic resonance were classified into LVT group. One hundred and sixty patients were selected as the non-LVT group using a 1∶3 propensity score matching based on age and gender. Multivariate logistic regression analysis was used to explore the influencing factors of LVT in patients with NIHF. A nomogram prediction model was constructed, and the area under (AUC) the receiver operating characteristic (ROC) curve was calculated to evaluate the predictive effect of the model. Results: A total of 211 patients were enrolled, with a median age of 40 years old and 160 males (76%). Compared with non-LVT group, LVT group had lower systolic blood pressure ((112±20) mmHg vs. (120±19) mmHg; 1 mmHg=0.133 kPa), lower left ventricular ejection fraction (LVEF; (27±12)% vs. (39±14)% ), lower proportion of patients with history of hypertension (28% (14/51) vs. 44% (70/160)) and atrial fibrillation (8% (4/51)vs.39% (62/160)), higher proportion of patients with New York Heart Association functional class Ⅲ to Ⅳ (class Ⅲ: 59% (30/51) vs. 41% (66/160); class Ⅳ: 28% (14/51) vs. 19% (31/160)), and larger left ventricular end-systolic diameter (LVESD; (56±14) mm vs. (50±15) mm). The levels of hemoglobin ((152±23) g/L vs. (142±30) g/L), D-dimer (508 (300, 1 105) μg/L vs. 158 (68, 379) μg/L), and N-terminal pro-brain natriuretic peptide (3 429 (2 462, 4 734) ng/L vs. 1 288 (422, 2 544) ng/L) were higher in LVT group than in non-LVT group (P all<0.05). LVT group had a higher proportion of patients using beta-blockers (92% (47/51) vs. 78% (124/160)), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors (88% (45/51) vs. 72% (115/160)), and anticoagulant drugs (98% (50/51) vs. 32% (51/160)) than non-LVT group (all P <0.05). Multivariate logistic regression showed that reduced LVEF (OR=1.08, 95%CI 1.02-1.15, P=0.008), decreased LVESD (OR=1.07, 95%CI 1.01-1.12, P=0.013), and increased D-dimer levels (OR=5.40, 95%CI 1.98-14.74, P=0.001) were independent influencing factors for LVT in patients with NIHF. The ROC curve showed that the AUC of the nomogram for predicting LVT in patients with NIHF was 0.793 (95%CI 0.710-0.876, P<0.001). Conclusion: Reduced LVEF, decreased LVESD, and elevated D-dimer are associated with LVT in NIHF patients. The predictive model developed based on the above indicators has certain value in predicting LVT in NIHF patients.

A Systematic Review and Meta-analysis of Efficacy and Safety of Mavacamten for the Treatment of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common hereditary cardiomyopathy. Mavacamten, a first-in-class cardiac myosin inhibitor, is considered to be a specific drug for the treatment of HCM. This meta-analysis aimed to assess the efficacy and safety of mavacamten in patients with HCM. PubMed, Cochrane Library, Embase and Clinical Trials.gov databases were searched from inception to February 6, 2024 for randomized controlled trials (RCTs) which compared the efficacy and safety between mavacamten and placebo in treating HCM. Six RCTs involving 732 patients were included in this meta-analysis. This meta-analysis showed that mavacamten improved the New York Heart Association (NYHA) function class [risk ratios (RR): 2.21, 95% confidence interval (CI): 1.48 to 3.30, p = 0.00001], Clinical Summary Score of the Kansas City Cardiomyopathy Questionnaire (KCCQ-CSS) scores [mean difference (MD): 9.33, 95% CI: 7.09 to 11.57, p < 0.00001] and composite functional end point (RR: 1.86, 95% CI: 1.25 to 2.78, p = 0.002). Meanwhile, mavacamten decreased N-terminal pro-B-type natriuretic peptide (NT-proBNP) (MD: -492.28, 95% CI: -611.55 to -373.02, p < 0.00001), cardiac troponin I (cTnI) (MD: -14.58, 95% CI: -26.98 to -2.17, p = 0.02) and Valsalva left ventricular outflow tract (LVOT) gradient (MD: -57.96, 95% CI: -82.15 to -33.78, p < 0.00001). The results for the incidence of ≥1 total emergent adverse event (TEAE) and ≥1 serious adverse event (SAE) showed that there was no significant difference between both groups (RR: 1.9, 95% CI: 0.97 to 1.24, p = 0.16) (RR: 1.06, 95% CI: 0.46 to 2.44, p = 0.90). Mavacamten has great efficacy for the treatment of HCM. Meanwhile, mavacamten did not increase the incidence of adverse events or serious adverse events.

Proteomic Signatures of Right Ventricular Outcomes in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a disease of progressive right ventricular (RV) failure with high morbidity and mortality. Our goal is to investigate proteomic features and pathways associated with RV-focused outcomes including mortality, RV dilation, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in PAH. Participants in a single-institution cohort with 3 years of follow-up underwent proteomic profiling of their plasma using 7288 aptamers (targeting 6467 unique human proteins). Partial least squares discriminant analysis was performed to assess global protein variation associated with mortality, RV dilation, and NT-proBNP levels. Differentially abundant proteins and enriched pathways associated with outcomes were identified following baseline adjustments. RV vulnerability models estimated associations for individuals with similar afterload following adjustment for pulmonary vascular resistance. A total of 117 participants with PAH were included. Partial least squares discriminant analysis of the proteome showed clear separation between survivors and nonsurvivors, participants with dilated versus nondilated RVs, and across NT-proBNP levels. Proteins and pathways involving the ECM (extracellular matrix) were upregulated in participants who died during follow-up, those with severe RV dilation, and those with higher levels of NT-proBNP. Pulmonary vascular resistance adjustment reinforced the importance of ECM proteins in the association with RV vulnerability, independent of afterload. These findings were confirmed in independent PAH cohorts with available plasma proteomics and RV tissue gene and protein expression. Distinct plasma proteomic profiles are associated with mortality, RV dilation, and NT-proBNP in PAH. Proteins and pathways governing tissue remodeling are strongly associated with poor outcomes, may mediate RV vulnerability to right heart failure, and represent promising candidates as biomarkers and potential therapeutic targets.

Effect of ertugliflozin on left ventricular function in type 2 diabetes and pre-heart failure: the Ertu-GLS randomized clinical trial

BackgroundThe therapeutic effects of ertugliflozin, a sodium-glucose cotransporter 2 inhibitor, on cardiovascular outcome are not fully understood. This study aimed to evaluate the efficacy and safety of ertugliflozin on cardiac function in people with type 2 diabetes and pre-heart failure.MethodsWe conducted a 24-week randomized, double-blind, placebo-controlled trial involving individuals with type 2 diabetes inadequately controlled with antidiabetic medications. Participants with left ventricular hypertrophy, E/e’ >15, or impaired left ventricular global longitudinal strain (LVGLS) were randomized 1:1 to receive either ertugliflozin (5 mg once daily) or a placebo. The primary outcome was the change in LVGLS. Secondary outcomes included changes in left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Prespecified exploratory outcomes, including angiotensin-converting enzyme 2 (ACE2) and angiotensin (1–7) levels, were also assessed.ResultsA total of 102 individuals (mean age, 63.9 ± 9.2 years; 38% women) were included. The ertugliflozin group showed a significant improvement in LVGLS (− 15.5 ± 3.1% to − 16.6 ± 2.8%, P = 0.004) compared to the placebo group (− 16.7 ± 2.7% to − 16.4 ± 2.6%, P = 0.509), with a significant between-group difference (P = 0.013). Improvements in LVMI and LVEF were also observed. Additionally, significant reductions in HbA1c, systolic blood pressure, whole-body and visceral fat, uric acid, proteinuria, N-terminal pro–B-type natriuretic peptide, and lipoprotein(a) were noted. ACE2 and angiotensin (1–7) levels significantly increased in the ertugliflozin group compared to the placebo group and correlated with changes in LVGLS [r = 0.456, P < 0.001 for ACE2; r = 0.541, P < 0.001 for angiotensin (1–7)]. Adverse events were similar between the two groups.ConclusionsThis study demonstrated that ertugliflozin has beneficial effects on left ventricular function in individuals with type 2 diabetes and pre-heart failure, and it provided insights into potential underlying mechanisms.Clinical trial registration ClinicalTrials.gov Identifier: NCT03717194.

Free fatty acids: independent predictors of long-term adverse cardiovascular outcomes in heart failure patients

BackgroundThe association between plasma free fatty acid (FFA) and the outcomes in the heart failure (HF) patients remains unclear.MethodsA cohort study among HF patients was performed. Plasma FFA was analyzed as both a continuous and a categorical variable (grouped by tertiles) to assess its association with composite cardiovascular (CV) death and HF hospitalization (CV death & HHP), CV death alone, and all-cause mortality (ACM) using Cox regression models. Subgroup analyses of HF patients with preserved ejection fraction (HFpEF) and mildly reduced/reduced ejection fraction (HFmrEF/HFrEF) were performed. This work also assessed the effectiveness of combining FFA and NT-pro BNP biomarkers for risk stratification by calculating the concordance index (C-index).ResultsAmong the 4,109 HF patients, FFA levels exceeding 0.4–0.42 mmol/L were associated with increased risks of the three outcomes. Patients in the highest FFA tertile faced greater risks than those in the lowest tertile. Adjusted hazard ratios were 1.32 (95% CI: 1.11–1.58) for CV death & HHP, 1.45 (95% CI: 1.16–1.82) for CV death, and 1.39 (95% CI: 1.15–1.68) for ACM, with a maximum follow-up of 8 years (median: 25 months). Subgroup analyses revealed that elevated FFA levels consistently predicted worse outcomes in both HFmrEF/HFrEF and HFpEF patients. The C-index for predicting outcomes was significantly greater when NT-pro BNP and FFA were combined than when NT-pro BNP was used alone (P < 0.01).ConclusionIncreased plasma FFA concentrations were independently associated with greater risks of CV death & HHP, CV death, and ACM among HF patients, irrespective of the ejection fraction. The combination of FFA and NT-pro BNP biomarkers significantly improved risk stratification in HF patients.

Efficacy and limitation of nonparoxysmal atrial fibrillation ablation in patients with heart failure with preserved ejection fraction.

Catheter ablation for atrial fibrillation (AF) reduces heart failure (HF) hospitalization in patients with HF with preserved ejection fraction (HFpEF). However, the long-term outcomes and subclinical HF after nonparoxysmal AF ablation in HFpEF patients have not been fully evaluated. One-hundred-ninety nonparoxysmal AF patients with left ventricular ejection fraction ≥50% who underwent first-time AF ablation were studied. HFpEF was diagnosed from a history of congestive HF and/or combined criteria of N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and transthoracic echocardiogram parameters, including average septal-lateral E/e' and tricuspid regurgitation peak velocity. Ninety-five patients with HFpEF (HFpEF group) were compared with 95 patients without HF (CNT group). Low voltage area (LVA) was defined as an area with a bipolar electrogram of <0.5 mV covering >5% of the total left atrial surface. The primary endpoint was a composite of death from any cause or hospitalization for worsening HF. The secondary endpoint was subclinical HFpEF defined from NT-proBNP concentration and average septal-lateral E/e' or tricuspid regurgitation peak velocity at 6-12 months after the procedure irrespective of the rhythm. Kaplan-Meier curves showed that the primary composite endpoint did not differ between the two groups (mean follow-up period 707 ± 75 days, log-rank p = 0.5330). However, significantly more patients in the HFpEF group reached the secondary endpoint (42 [44%] vs. 13 [14%], p < 0.0001). Multivariate analysis revealed that a high preablation NT-proBNP (odds ratio [OR] 1.001, 95% confidence interval [CI] 1.001-1.002, p = 0.0040) and the existence of LVA (OR 5.983, 95% CI 1.463-31.768, p = 0.0194) independently predicted the secondary endpoint in HFpEF patients. After nonparoxysmal AF ablation, mortality of HFpEF patients was not inferior compared to patients without coexisting HF. However, subclinical HF occasionally persisted especially in HFpEF patients with a high preprocedure NT-proBNP concentration and LVA.

Cardiovascular management of patients undergoing noncardiac surgery

The risk assessment of patients with cardiovascular diseases before noncardiac surgery (NCS) is particularly relevant in cardiology because of the frequency and the involvement of different disciplines. The risk is determined by the operation itself and the disease or risk profile, including the patient's age. Specialist preoperative consultation can therefore remain limited if the surgery-related risk is low. The subjective symptoms (exercise tolerance) and also the determination of the cardiac biomarkers N‑terminal pro-brain natriuretic peptide (NT-proBNP) and troponin are particularly relevant for assessing the indications for an instrumental or specialist examination. Cardiovascular drug treatment should predominantly be continued perioperatively but not initiated just for the operation. There are practical guidelines for pausing oral anticoagulation, whereby a general heparin bridging is no longer recommended.

Clinical Correlates and Prognostic Impact of Cognitive Dysfunction in Patients With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF.

Cognitive impairment is common in patients with heart failure and preserved ejection fraction but its clinical correlates and prognostic associations are poorly understood. We analyzed cognitive function, using the Mini-Mental State Examination (MMSE), in patients with heart failure and preserved ejection fraction enrolled in a prespecified substudy of the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction). Logistic regression analyses were performed to determine the variables associated with lower MMSE scores at baseline and postbaseline decline in MMSE scores at 48 weeks. Cox proportional hazards regression and semiparametric proportional rates models were used to examine the risk of clinical outcomes related to baseline MMSE scores, and decline in MMSE scores during follow-up, adjusted for prognostic variables including NT-proBNP (N-terminal pro-B-type natriuretic peptide). At baseline, cognitive function was normal (MMSE score 28-30) in 1809 of 2895 patients (62.5%), borderline (score 24-27) in 794 (27.4%), and impaired (score <24) in 292 (10.1%). Variables associated with both a lower MMSE score at baseline and a decline in score from baseline included older age, a history of stroke or transient ischemia attack, and lower serum albumin. Compared with those with baseline MMSE scores of 28 to 30, patients in the lower MMSE score categories had a stepwise increase in the risk of the composite of time to first HF hospitalization or cardiovascular death, with an adjusted hazard ratio of 1.27 (95% CI, 1.06-1.53) for those with scores of 24 to 27 and 1.58 (95% CI, 1.21-2.06) for those with scores <24, respectively. These associations were also found for the individual components of the composite and all-cause death. Likewise, cognitive impairment was associated with a 50% higher risk of total (first and repeat) heart failure hospitalizations and cardiovascular deaths. Examining the change in MMSE score from baseline, a decrease in MMSE score during follow-up was associated with a higher risk of death. In patients with heart failure and preserved ejection fraction, even modest baseline impairment of cognitive function was associated with worse outcomes, including death. A decline in MMSE score during follow-up was a strong predictor of mortality, independent of other prognostic variables.

Efficacy and Safety of Ivabradine for Patients With AcuteHeart Failure: Meta-Analysis of Randomized Controlled Trials.

The efficacy and safety of Ivabradine for patients with acute heart failure (AHF) is controversial, and there are few clinical trials addressing this topic. We performed this meta-analysis to evaluate efficacy and safety of Ivabradine treatment for patients with acute heart failure. We obtained data for controlled trials using the PubMed, Cochrane Library, EMBASE, and Clinical Trials.gov databases. The efficacy endpoints included change in heart rate, brain natriuretic peptide (BNP) levels, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, ejection fraction (EF) values, and a 6-min walk distance. The safety endpoints included mortality, cardiogenic mortality, incidents of hospital readmission, bradycardia, and atrial fibrillation. Ten randomized controlled trials (RCTs) met our criteria, and data from 656 patients were included for the study. Ivabradine treatment significantly decreased heart rate and BNP and NT-proBNP levels compared with those seen in the control group. EF values were significantly increased upon ivabradine treatment. No significant differences were observed in the endpoints of the 6-min walk distance, all-cause mortality, cardiogenic mortality, incidents of hospital readmission, bradycardia, and atrial fibrillation data between ivabradine treated and control groups. Ivabradine can reduce heart rate and BNP and NT-pro BNP levels and elevate EF values and 6-min walk distance data significantly in acute heart failure patients. It also exhibits a stable safety profile, with similar risks of all-cause mortality, cardiogenic mortality, incidents of readmission, and major adverse cardiovascular effects compared with those of the control group.

The Role of Natriuretic Peptides in the Management of Heart Failure with a Focus on the Patient with Diabetes.

Natriuretic peptides (NPs) are polypeptide hormones involved in the homeostasis of the cardiovascular system. They are produced by cardiomyocytes and regulate circulating blood volume and sodium concentration. Clinically, measurements of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are recommended by international guidelines as evidence is accumulating on their usefulness. They have a high negative predictive value, and in the setting of low NPs, a diagnosis of heart failure (HF) can be safely excluded in both emergency (BNP < 100 pg/mL, NT-proBNP < 300 pg/mL) and outpatient settings (BNP < 35 pg/mL and NT-proBNP < 125 pg/mL). Moreover, the 2023 consensus from the European Society of Cardiology suggests threshold values for inclusion diagnosis. These values are also associated with increased risks of major cardiovascular events, cardiovascular mortality, and all-cause mortality whether measured in inpatient or outpatient settings. Among patients without known HF, but at high risk of developing it (e.g., in the setting of diabetes mellitus, hypertension, or atherosclerotic cardiovascular disease), NPs may be useful in stratifying cardiovascular risk, optimizing therapy, and reducing the risk of developing overt HF. In the diabetes setting, risk stratification with the use of these peptides can guide the physician to a more informed and appropriate therapeutic choice as recommended by guidelines. Notably, NP levels should be carefully interpreted in light of certain conditions that may affect their reliability, such as chronic kidney disease and obesity, as well as demographic variables, including age and sex. In conclusion, NPs are useful in the diagnosis and prognosis of HF, but they also offer advantages in the primary prevention setting.