Abstract Decision making in acute chest pain remains challenging despite normal (<99th percentile) high-sensitivity troponin (hs-cTn). Some studies suggest that undetectable hs-cTn, far below the ...99th percentile, might rule out acute coronary syndrome. We investigated clinical data in comparison to undetectable hs-cTnT. The study comprised of 682 patients (November 2010/September 2011) presenting at the emergency department with chest pain and normal hs-cTnT (<14 ng/L). The main endpoint was major adverse cardiac events (MACE: death, myocardial infarction, readmission for unstable angina or revascularization) at a 4-year median follow-up; secondary endpoint was 30-day MACE. A clinical score was built by assigning points according to hazard ratios of the independent predictive variables: 1 point (male and effort-related pain), and 2 points (recurrent pain and prior ischemic heart disease).The negative predictive values of the clinical score and undetectable hs-cTnT (<5 ng/L), were tested. A total of 72 (10.6%) patients suffered long-term MACE. The C-statistics of the clinical score for long-term (0.75) and 30-day (0.88) MACE were higher than with the TIMI risk (0.68, 0.77) or GRACE (0.50, 0.47) scores. Likewise, the negative predictive values of score= 0 (97.5%, 100%) and ≤1 point (95.9%, 100%) were higher than using undetectable hs-cTnT (91.9%, 98.1%). Both a clinical score of 0 and ≤1 classified better patients at risk of MACE (p=0.0001, log rank test) than hs-cTnT<5 ng/L (p=0.06). In conclusion, clinical data can guide decision making and perform at least equally well as undetectable hs-cTnT, in patients presenting at the emergency department with chest pain and normal hs-cTnT.
Acute kidney injury (AKI) is a common complication after coronary angiography. Early biomarkers of this disease are needed since increase in serum creatinine levels is a late marker. To assess the ...usefulness of urinary kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL) and liver-type fatty acid-binding protein (uL-FABP) for early detection of AKI in these patients, comparing their performance with another group of cardiac surgery patients. Biomarkers were measured in 193 patients, 12 h after intervention. In the ROC analysis, AUC for KIM-1, NGAL and L-FABP was 0.713, 0.958 and 0.642, respectively, in the coronary angiography group, and 0.716, 0.916 and 0.743 in the cardiac surgery group. Urinary KIM-1 12 h after intervention is predictive of AKI in adult patients undergoing coronary angiography, but NGAL shows higher sensitivity and specificity. L-FABP provides inferior discrimination for AKI than KIM-1 or NGAL in contrast to its performance after cardiac surgery. This is the first study showing the predictive capacity of KIM-1 for AKI after coronary angiography. Further studies are still needed to answer relevant questions about the clinical utility of biomarkers for AKI in different clinical settings.
The pathophysiology of changes in estimated glomerular filtration rate (eGFR) in acute heart failure (AHF) is complex and multifactorial. We evaluated the associated mortality risk of early changes ...in eGFR across baseline renal function on admission and early changes in natriuretic peptides in patients admitted with AHF.
We retrospectively evaluated 2,070 patients admitted with AHF. Renal dysfunction on admission was defined as eGFR<60 ml/min/1.73m2 and successful decongestion as NT-proBNP decreased >30% from baseline. We assessed the mortality risk associated with eGFR changes from baseline at 48–72 h after admission (ΔeGFR%) according to baseline renal function, and NT-proBNP changes at 48–72 h through Cox regression analyses.
The mean age was 74.4 ± 11.2 years, and 930 (44.9%) were women. The proportion of admission eGFR<60 ml/min/1.73m2 and 48–72 h changes in NT-proBNP>30% were 50.5% and 32.8%, respectively. At a median follow-up of 1.75 years, 928 deaths were registered. In the whole sample, changes in renal function were not associated with mortality (p = 0.208). The adjusted analysis revealed that the risk of mortality related to ΔeGFR% was heterogeneous across baseline renal function and changes in NT-proBNP (p-value for interaction=0.003). ΔeGFR% was not associated with mortality in patients with baseline eGFR≥60 ml/min/1.73m2. In those with eGFR<60 ml/min/1.73m2, a decrease in eGFR was associated with higher mortality, particularly in those with a reduction in NT-proBNP<30%.
In patients with AHF, early ΔeGFR% was associated with the risk of long-term mortality only in patients with renal dysfunction on admission and no early decline in NT-proBNP.
Display omitted eGFR: estimated glomerular filtration rate assessed by CKD-EPI equation; h: hours; NT-proBNP: N-terminal pro-brain natriuretic peptide.
Heart failure (HF) is a dominant health problem with an overall poor prognosis. Natriuretic peptides (NPs) are upregulated in HF as a compensatory mechanism. They have been extensively used for ...diagnosis and risk stratification.
This review addresses the history and physiology of NPs in order to understand their current role in clinical practice. It further provides a detailed and updated narrative review on the utility of those biomarkers for risk stratification, monitoring, and guiding therapy in HF.
NPs show excellent predictive ability in heart failure patients, both in acute and chronic settings. Understanding their pathophysiology and their modifications in specific situations is key for an adequate interpretation in specific clinical scenarios in which their prognostic value may be weaker or less well evaluated. To better promote risk stratification in HF, NPs should be integrated with other predictive tools to develop multiparametric risk models. Both inequalities of access to NPs and evidence caveats and limitations will need to be addressed by future research in the coming years.
Aim Elevated brain natriuretic peptide (BNP) and tumour marker antigen carbohydrate 125 (CA125) levels have shown to be associated with higher risk for adverse outcomes in patients with acute heart ...failure (AHF). Nevertheless, no attempt has been made to explore the utility of combining these two biomarkers. We sought to assess whether CA125 adds prognostic value to BNP in predicting 6-month all-cause mortality in patients with AHF. Methods and results We analysed 1111 consecutive patients admitted for AHF. Antigen carbohydrate 125 (U/mL) and BNP (pg/mL) were measured at a median of 72 ± 12 h after instauration of treatment. Antigen carbohydrate 125 and BNP were dichotomized based on proposed prognostic cutpoints, and a variable with four categories was formed (BNP–CA125): C1 = BNP < 350 and CA125 < 60 (n = 394); C2 = BNP ≥ 350 and CA125 < 60 (n = 165); C3 = BNP < 350 and CA125 ≥ 60 (n = 331); and C4 = BNP ≥ 350 and CA125 ≥ 60 (n = 221). The independent association between BNP–CA125 and mortality was assessed with the Cox regression analysis, and their added predictive ability tested by the integrated discrimination improvement (IDI) index. At 6 months, 181 deaths (16.3%) were identified. The cumulative rate of mortality was lower for patients in C1 (7.8%), intermediate for C2 and C3 (17.8% and 16.9%, respectively), and higher for C4 (37.2%), and P-value for trend <0.001. After adjusting for established risk factors, the highest risk was observed when both biomarkers were elevated (C4 vs. C1: HR = 4.05, 95% CI = 2.54–6.45; P < 0.001) and intermediate when only one of them was elevated: (C2 vs. C1: HR = 1.71, 95% CI = 1.00–2.93; P = 0.050) and (C3 vs. C1: HR = 2.10, 95% CI = 1.30–3.39; P = 0.002). Moreover, when CA125 was added to the clinical model + BNP, a 10.4% (P < 0.0001) improvement in the IDI (on the relative scale) was found. Conclusion In patients admitted with AHF, CA125 added prognostic value beyond the information provided by BNP, and thus, their combination enables better 6-month risk stratification.
•Breath tests are easy and noninvasive methods for identifying small intestinal microbiota overgrowth. These tools could be a potential method for quantifying the contribution of intestinal bacteria ...in the pathophysiology of heart failure (HF).•This study is the first to show that small intestinal bacterial overgrowth, assessed by exhaled concentrations of hydrogen and methane after a lactulose test, is highly prevalent in patients with HF.•In this cohort, exhaled concentration of hydrogen was positive and independently associated with higher risk of the composite of all-cause death/admissions and with recurrent hospitalizations.•Patients with higher exhaled hydrogen concentration after a lactulose test may identify a subgroup of patients with greater contribution of gut microbiota in the pathophysiology of HF that would benefit from specific treatments such as modification of microbiota composition, modulation of the immune response, or even intensifying HF drug therapy.
Recent evidence endorses gut microbiota dysregulation in the pathophysiology of heart failure (HF). Small intestinal bacterial overgrowth (SIBO) might be present in HF and associated with poor clinical outcomes. Lactulose breath testing is a simple noninvasive test that has been advocated as a reliable indicator of SIBO. In patients with HF, we aimed to evaluate the association with clinical outcomes of the exhaled hydrogen (H2) and methane (CH4) concentrations through the lactulose breath test.
We included 102 patients with HF in which lactulose SIBO breath tests were assessed. Cumulative gas was quantified by the area under the receiver operating characteristic curve of CH4 (AUC-CH4) and H2 (AUC-H2). Clinical end points included the composite of all-cause death with either all-cause or HF hospitalizations, recurrent all-cause hospitalizations, and recurrent HF hospitalizations. Medians (interquartile ranges) of AUC-H2 and AUC-CH4 were 1290 U (520-2430) and 985 U (450-2120), respectively. In multivariable analysis, AUC-H2 (per 1000 U) was associated with all-cause death/all-cause hospitalization (hazard ratio HR 1.21, 95% CI 1.04–1.40; P = .012), all-cause death/HF hospitalization (HR 1.20, 95% CI 1.03–1.40; P = .021), and an increase in the rate of recurrent all-cause (incidence rate ratio IRR 1.31, 95% CI 1.14–1.51; P < .001) and HF (IRR 1.41, 95% CI 1.15–1.72; P = .001) hospitalizations. AUC-CH4 was not associated with any of these end points.
AUC-H2, a safe and noninvasive method for SIBO estimation, is associated with higher risk of long-term adverse clinical events in patients with HF. In contrast, AUC-CH4 did not show any prognostic value.
Decision-making is challenging in patients with chest pain and normal high-sensitivity cardiac troponin T (hs-cTnT; <99th percentile; <14 ng/L) at hospital arrival. Most of these patients might be ...discharged early. We investigated clinical data and hs-cTnT concentrations for risk stratification. This is a retrospective study including 4476 consecutive patients presenting to the emergency department with chest pain and first normal hs-cTnT. The primary endpoint was one-year death or acute myocardial infarction, and the secondary endpoint added urgent revascularization. The number of primary and secondary endpoints was 173 (3.9%) and 252 (5.6%). Mean hs-cTnT concentrations were 6.9 ± 2.5 ng/L. Undetectable (<5 ng/L) hs-cTnT (
= 1847, 41%) had optimal negative predictive value (99.1%) but suboptimal sensitivity (90.2%) and discrimination accuracy (AUC = 0.664) for the primary endpoint. Multivariable analysis was used to identify the predictive clinical variables. The clinical model showed good discrimination accuracy (AUC = 0.810). The addition of undetectable hs-cTnT (≥ or <5 ng/L; HR, hazard ratio = 3.80; 95% CI, confidence interval 2.27-6.35;
= 0.00001) outperformed the clinical model alone (AUC = 0.836,
= 0.002 compared to the clinical model). Measurable hs-cTnT concentrations (between detection limit and 99th percentile; per 0.1 ng/L, HR = 1.13; CI 1.06-1.20;
= 0.0001) provided further predictive information (AUC = 0.844;
= 0.05 compared to the clinical plus undetectable hs-cTnT model). The results were reproducible for the secondary endpoint and 30-day events. Clinical assessment, undetectable hs-cTnT and measurable hs-cTnT concentrations must be considered for decision-making after a single negative hs-cTnT result in patients presenting to the emergency department with acute chest pain.
Abstract Background and Aims Chronic Kidney Disease (CKD) is recognized as a health problem in the general population. The worldwide incidence of chronic kidney disease (CKD) is increasing, driven by ...aging populations and a higher prevalence of type 2 diabetes (T2D) and hypertension. The CKD is generally asymptomatic, and the diagnosis depends on the laboratory monitoring of the patients. The KDIGO consensus statement recommend the implementation of screening programs in patients at high risk of CKD development. We present the first results of a sentinel surveillance program of CKD in a healthcare area for detecting undiagnosed CKD in patients at risk. Method Our health department covers the metropolitan area of Valencia, attending 341, 972 citizens through 31 primary care centers. A CKD screening program has been established in this population based on a middleware clinical decision support (CDS) system “CDS-Ripple Down - Abbott Diagnostics” integrated in an electronic request system and in the electronic health records. When a general practitioner doctor order a lab test, the middleware CDS system detects high risk patients for CKD defined by age: >65 to <90, diabetes mellitus, hypertension, or obesity. Automatically, the system adds serum creatinine, estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR) and urine sediment analysis if it has not been requested (sentinel program). Then, the patients are classified into KDIGO stages based on eGFR and UACR and the CDS system detect those with progression (Fig. 1). Only patients with UACR > 300 mg/g, eGFR < 30 ml/min/1.73, or progression were referred to nephrology. A nephrologist then decides whether patients require a face-to-face visit or provides recommendations to primary care physicians. Results From 01/11/2023 to 31/12/2023, 4, 989 reports were generated by CDS-system corresponding to 122 laboratory test per day. 99, 33% were added by the sentinel program. 3, 970 (79.6%) patients did not have CKD (KDIGO G1-2 or UACR <30 mg/g), 887 (17.8%) patients CKD not suitable for referral to Nephrology (KDIGO 3 and UACR 30-300 mg/g without progression, and 130 (2, 6%) were referred to Nephrology. (Fig. 2) Patients referred to Nephrology had a median age of 79 years IQR: 72-85, 68 (52, 3%) were women. Twenty-seven patients (20%) were classified as KDIGO G2 A3, 19 (14, 6%) as KDIGO G4 A1 and 18 (13, 8) as KDIGO G2 A2. Fifty-seven patients (43, 8%) have been scheduled to face-to-face at nephrology consultation (1.1% of the total sample), and 73 (56, 1%) have been referred to their primary care doctors with recommendations (1.5% of the total sample). Among the patients referred to Nephrology by the CDS system, the reasons for not scheduling a face-to-face visit in Nephrology were mild decrease in eGFR (n = 18), UACR A2 (n = 24), elderly patients with low Kidney Failure Risk Equation (n = 5), urological pathology (n = 10), dependent patient and/or palliative situation (n = 5) and other causes (n = 11). Conclusion A novel CKD automatic screening method for capturing undiagnosed CKD among patients at risk has been developed. After screening around 5 000 patients at risk in two months, 2.6% of them presented criteria for referral to Nephrology. Only 1.4% required face-to-face visit. If we continue at this screening rate, it is expected that half of our population at risk of developing CKD will have been screened in less than one year. Computer systems with algorithms programmed and improved by a multidisciplinary team can establish a sentinel route (reviewing patients medical records), interpreting analytical values (calculating progressions, KDIGO stages, KFRE risk...) and producing automatic interpretive reports that integrates all the elements of CKD clinical attention allowing us to carry out this population screening.
Background Although high-sensitivity troponins allow early diagnosis of acute myocardial infarction, their role for identification of acute coronary syndrome in patients with normal conventional ...troponin remains unclear. Methods and results A total of 446 patients presenting to the emergency department with chest pain and normal troponin (common practice assays) in 2 serial samples were included. Both samples were also centrally analyzed for high-sensitivity troponin T (hs-TnT) (Roche Diagnostics, Basel, Switzerland). Detection (> 3 ng/L) and 99th percentile (≥ 14 ng/L) cutoffs of the maximum hs-TnT levels (hs-TnTmax) were considered. The end points were acute coronary syndrome diagnosis and the composite of in-hospital revascularization or 30-day cardiac events. Results Acute coronary syndrome was adjudicated to 84 patients (19%), and 62 (14%) had the composite end point. In univariate setting, hs-TnTmax > 3 ng/L exhibited high sensitivity (87% and 92%, respectively) and negative predictive value (93% and 97%) for both end points, whereas hs-TnTmax ≥ 14 ng/L provided high specificity (90% and 89%), although low positive predictive values (40% and 33%). After adjusting for clinical (pain characteristics and risk factors) and electrocardiographic data, there was a stepped increase of risk across hs-TnTmax categories (≤ 3, > 3 but < 14, and ≥ 14 ng/L) for both end points; however, the discriminative capacity added was marginal (integrated discrimination improvement of 2.6% and 3.5%, respectively). Conclusions Clinical and electrocardiographic data remain the most important tools for the evaluation of patients with chest pain and with no or minimal myocardial damage. The main contribution of hs-TnT is the high negative predictive value of undetectable levels (≤ 3 ng/L).
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