High-sensitivity Troponin Research Articles

Clinical and prognostic significance of central and obstructive apnoeas in patients with transthyretin cardiac amyloidosis

Abstract Aims Central apnoea (CA) and obstructive apnoea (OA) are highly prevalent in patients with chronic heart failure (HF), and transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized HF aetiology. This study aims to investigate the prevalence and impact of CA and OA in patients with ATTR-CA. Methods and results Consecutive patients with ATTR-CA who underwent 24 h ambulatory cardiorespiratory monitoring were enlisted for an evaluation of the prevalence and severity of breathing disorders. The severity of these disorders was quantified using the apnoea–hypopnoea index (AHI). Accordingly, the patients were categorized as having normal breathing (NB, AHI <5 events/h), OA (AHI ≥5 events/h with >50% being obstructive), or CA (AHI >5 events/h with ≥50% being central). The primary endpoint at follow-up was all-cause mortality. Out of 142 patients enrolled (n = 142, aged 77 ± 7 years, 91% males, 96% wild-type ATTR-CA), considering the 24 h monitoring, 20% had NB (39% at daytime and 8% at nighttime), 35% had CA (45% at daytime and 39% at nighttime), and 45% had OA (25% at daytime and 54% at nighttime). After a median 2.3-year (1.4–3.3 years) follow-up, 24 h, daytime, and nighttime AHIs were higher in non-survivors vs. survivors (all P < 0.05), independently of the prevalent apnoea type (P = 0.64). At multivariable regression analysis (adjusted for the possible clinical, echocardiographic, and biohumoral confounders), nighttime AHI ≥30 events/h {hazard ratio 2.37 [95% confidence interval (CI) 1.07–5.23], P = 0.033} and high-sensitivity troponin T [hazard ratio 2.43 (95% CI 1.42–4.17), P = 0.001] were predictors of mortality. Conclusion Both CA and OA are highly prevalent, both at daytime and nighttime, in patients with ATTR-CA and are associated with higher mortality.

Impact of high-sensitivity cardiac troponin I assay imprecision on the safety of a single-sample rule-out approach for myocardial infarction

Impact of high-sensitivity cardiac troponin I assay imprecision on the safety of a single-sample rule-out approach for myocardial infarction

Six-year change in high-sensitivity cardiac troponin T with subsequent stroke risk in the general population

BackgroundThe association between change in high-sensitivity cardiac troponin T (hs-cTnT) and stroke risk in the general population remains unknown. We aimed to assess the association of a 6-year change in...

Associations of Hypertension and Orthostatic Hypotension With Subclinical Cardiovascular Disease.

Orthostatic hypotension is associated with cardiovascular disease. It remains unclear if low standing blood pressure or high seated blood pressure is responsible for this association. We compared associations of orthostatic hypotension and hypertension with high-sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic peptide. We performed a secondary analysis of the Study to Understand Fall Reduction and Vitamin D in You, a randomized controlled trial funded by the National Institute on Aging, between July 2015 and May 2019. Participants were community-dwelling adults, 70 years or older. Blood tests for high-sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic peptide were drawn at visits concurrent with blood pressure measurements. Secondary analysis occurred in 2023. We determined associations between blood pressure phenotypes and cardiac biomarkers. Of 674 participants (mean age 76.5 ± 5.4 years, 43% female, 17.2% Black race), 29.1% had prior cardiovascular disease. Participants with seated hypertension had 10.1% greater high-sensitivity cardiac troponin I (95% confidence interval = 3.8-16.9) and 11.0% greater N-terminal pro-B-type natriuretic peptide (4.0-18.6) than those without seated hypertension. Participants with standing hypertension had 8.6% (2.7-14.9) greater high-sensitivity cardiac troponin I and 11.8% greater N-terminal pro-B-type natriuretic peptide (5.1-18.9) than those without standing hypertension. Hypotensive phenotypes were not associated with either biomarker. Both seated and standing hypertension were associated with greater high-sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic peptide, but hypotensive phenotypes were not. Hypoperfusion may not be the principal mechanism behind subclinical cardiac injury among older adults with orthostatic hypotension.

The Effect of Low-Intensity Interval Exercise with Blood Flow Restriction on Plasma Cardiac Troponin: A Cross-Design Trial.

Low-intensity training with blood flow restriction (BFR) training could induce endurance adaptations, its impact on myocardial markers is still unclear compared to training without BFR. Consequently, the influence of low-intensity interval exercise with and without BFR and high-intensity interval exercise (HIIE) on cardiac troponin was determined in this study. Twelve physically active males between 18 and 26 years volunteered as participants. The participants completed 3 exercise tests in random order, which included 40% VO2max low-intensity cycling without BFR (group L), 40% VO2max low-intensity cycling with BFR set at 60% limb occlusion pressure (LOP) (group B), and 80% VO2max high-intensity cycling without BFR (group H). Participant muscle oxygen, blood flow, oxygen uptake, heart rate (HR), perceived exertion (RPE) rating, and pain levels were determined before and after exercise, after cuff inflation, and pre- and post-each exercise. Moreover, before each protocol, immediately after the exercises, and 3-4 hours after each exercise, elbow vein blood samples were collected to evaluate lactate (LA) and high-sensitivity cardiac troponin T (cTnT). Increased LA was recorded after exercise by the individuals in group H, which was more significant than in group B. Moreover, group B documented a more significant LA increment than group L (P < .05). The peak cTnT of groups B and H after exercise was significantly higher (P < .05). Furthermore, the increase was more significant than the values recorded by group L (P < .05). The present study demonstrated that low-intensity interval exercise combined with BFR could cause cTnT elevations compared to training without BFR. The increase was similar to HIIE protocols.

Biomarkers of atrial fibrillation-related pathways and left atrial structure and function in an overweight and obese population.

Exploring longitudinal associations of blood biomarkers with left atrial (LA) structure and function can enhance our understanding of atrial fibrillation (AF) etiopathogenesis. We studied 532 participants of the PREDIMED-Plus trial, a multicenter randomized trial in overweight and obese adults with metabolic syndrome. At baseline, 3 and 5 years after randomization, participants underwent transthoracic echocardiography and provided blood for serum biomarker measurements [propeptide of procollagen type I (PICP), high-sensitivity (hs) troponin T (hsTnT), hs C-reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP)]. Outcomes of interest included LA peak systolic longitudinal strain (LA PSLS), LA volume index (LAVi), LA function index (LAFi), and LA stiffness index (LASi). We performed cross-sectional and longitudinal analyses to evaluate relationships between log-transformed biomarkers and echocardiographic measurements using multiple linear regression and mixed models. The participants in this analysis had a mean age of 65.0 (SD 4.8) years, and 40% were females. At baseline, increased NT-proBNP and hsTnT were associated with larger LAVi and worse LA function as measured by the LAFi, LASi, and LA PSLS. Longitudinally, higher NT-proBNP, but not higher hsTnT, was associated with increased LAVi and worsening LA function. Over 5 years, 1 unit increase in log(NT-proBNP) was associated with steeper decline in LA PSLS (-0.19%, 95% CI -0.35%, -0.02%) and greater increase in LAVi (0.28 mL/m2, 95% CI 0.10, 0.45) each year. PICP, hsCRP, and 3-NT did not show consistently significant associations with LA outcomes at baseline and through 5 years. In an overweight and obese population, higher NT-proBNP was associated with LA volume enlargement and worsening LA function over 5 years. The implications of these findings for the prevention and prediction of AF warrant further investigation.

Donor-derived Cell-free DNA Evaluation in Pediatric Heart Transplant Recipients: A Single-center 12-mo Experience.

Endomyocardial biopsy (EMB) is considered the gold-standard method to diagnose rejection after heart transplantation. However, the many disadvantages and potential complications of this test restrict its routine application, particularly in pediatric patients. Donor-derived cell-free DNA (dd-cfDNA), released by the transplanted heart as result of cellular injury, is emerging as a biomarker of tissue damage involved in ischemia/reperfusion injury and posttransplant rejection. In the present study, we systematically evaluated dd-cfDNA levels in pediatric heart transplant patients coming for follow-up visits to our clinic for 12 mo, with the aim of determining whether dd-cfDNA monitoring could be efficiently applied and integrated into the posttransplant management of rejection in pediatric recipients. Twenty-nine patients were enrolled, and cfDNA was obtained from 158 blood samples collected during posttransplant follow-up. dd-cfDNA% was determined with a droplet-digital polymerase chain reaction assay. EMB scores, donor-specific antibody measurements, and distress marker quantification were correlated with dd-cfDNA, together with echocardiogram information. The percentage of dd-cfDNA increased when EMBs scored positive for rejection (P = 0.0002) and donor-specific antibodies were present (P = 0.0010). N-terminal pro-B-type natriuretic peptide and high-sensitive troponin I elevation were significantly associated with dd-cfDNA release (P = 0.02 and P < 0.0001, respectively), as were reduced isovolumetric relaxation time (P = 0.0031), signs of heart failure (P = 0.0018), and treatment for rejection (P = 0.0017). By determining a positive threshold for rejection at 0.55%, the test had a negative predictive value maximized at 100%. Collectively, results indicate that dd-cfDNA monitoring has a high negative prognostic value, suggesting that in heart transplanted children with dd-cfDNA levels of <0.55% threshold, protocol EMBs may be postponed.

Cardiac biomarker concentrations in cats with elevated pancreatic lipase concentrations.

Cardiac biomarker concentrations are elevated in dogs with pancreatitis, but it is unknown if this is also the case for cats. The serum feline pancreatic lipase immunoreactivity (fPLI) of serum samples from 60 cats was quantified using the Spec fPL assay. Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (HST) concentrations were also measured using commercial assays. Five of 20 cats with fPLI concentrations of 8.8mg/L or more had above reference interval NT-proBNP concentrations. Serum NT-proBNP concentrations were not correlated with fPLI concentrations (p = 0.31) and were not different in each diagnostic category for fPLI results (p = 0.24). Serum HST concentrations were positively correlated with fPLI concentrations (r = 0.278, 95% confidence interval: 0.02‒0.50, p = 0.03). However, they were not significantly different in each diagnostic category for fPLI results (p = 0.16). Unidentified co-variates could contribute to the association between fPLI and cardiac biomarker concentrations. Cats with elevated fPLI concentrations may have elevated cardiac biomarker concentrations.

Soluble suppression of tumorigenicity 2 associated with contrast-induced acute kidney injury in patients with STEMI.

Contrast-induced acute kidney injury (CI-AKI) is a common complication after percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). Soluble suppression of tumorigenicity 2 (sST2) is associated with AKI. However, the relationship between sST2 and CI-AKI is unclear. This study aimed to investigate the relationship between sST2 and CI-AKI in patients with STEMI. This was a single-center retrospective observational study. Patients diagnosed with STEMI in the Yichun People's Hospital from February 2020 to May 2024 were continuously included. CI-AKI was defined as an increase in serum creatinine of at least 50% or 0.3mg/dL from baseline within 48-72h after contrast exposure. The incidence of CI-AKI after PCI was 12.4% (98/791). Univariate analysis showed that age, fasting plasma glucose, diabetes mellitus, Killip class, left ventricular ejection fraction, estimated glomerular filtration rate, high sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, and sST2 were associated with CI-AKI. The above factors were included in a multivariate analysis, which showed that sST2 was an independent factor for CI-AKI after PCI. The restricted cubic splines showed a nonlinear dose-response relationship between sST2 and CI-AKI (P < 0.001). The integration of the sST2 could significantly improve the ability of the model to identify CI-AKI (NRI 0.681, 95% CI 0.474-0.887; IDI 0.063, 95% CI 0.038-0.099). Elevated sST2 is an independent risk factor for CI-AKI after PCI in patients with STEMI. Integration of sST2 can significantly improve the risk model for CI-AKI.

Biomarkers of COVID-19 short-term worsening: a multiparameter analysis within the prospective multicenter COVIDeF cohort.

During a pandemic like COVID-19, hospital resources are constrained and accurate severity triage of the patients is required. The objective of this study is to estimate the predictive performances of candidate biomarkers for short-term worsening (STW) of COVID-19. Prospective, multicenter (20 hospitals in Paris) cohort study of consecutive COVID-19 patients with systematic biobanking at admission, during the first waves of COVID-19 in France in 2020 (COVIDeF cohort). Consecutive COVID-19 patients were screened for inclusion. They were excluded in presence of severity criteria defined by either an ICU admission, mechanical ventilation (including noninvasive ventilation), acute respiratory distress, or in-hospital death before sampling. Routine blood tests measured during usual care and centralized systematic measurement of creatine kinase, C-reactive protein (CRP), procalcitonin, soluble urokinase plasminogen activator receptor (suPAR), high-sensitive troponin T (TnT-hs), N terminal pro-B natriuretic peptide (NT-proBNP), calprotectin, platelet factor 4, mid-regional pro-adrenomedullin (MR-proADM), and proendothelin were performed. The primary outcome was STW, defined by a severity criteria within 7 days. A backward stepwise logistic regression model and a 'best subset' approach were used to identify independent association, and the area under the receiving operator characteristics (AUROC) was computed. Five hundred and eleven patients were analyzed, of whom 60 (11.7%) experienced STW. Median time to occurrence of a severity criteria was 3 days. At admission, lower values of eosinophils, lymphocytes, platelets, alanine aminotransferase, and higher values of neutrophils, creatinine, urea, CRP, TnT-hs, suPAR, NT-proBNP, calprotectin, procalcitonin, MR-proADM, and proendothelin were predictive of worsening. Stepwise logistic regression identified three biomarkers significantly associated with worsening: CRP [adjusted odds ratio (aOR): 1.10, 95% confidence interval (95% CI): 1.06-1.15 for a 10-unit increase, AUROC: 0.73 (0.66-0.79)], procalcitonin [aOR: 0.42, 95% CI: 0.22-0.81, AUROC: 0.69 (0.64-0.88)], and MR-proADM [aOR: 2.85, 95% CI: 1.74-4.69, AUROC: 0.75 (0.69-0.81)]. These biomarkers outperformed clinical variables except diabetes and cancer comorbidities. In this multicenter prospective study that assessed a large panel of biomarkers for COVID-19 patients, CRP, procalcitonin, and MR-proADM were independently associated with the risk of STW. ClinicalTrials.gov NCT04352348.

The role of emergency department crowding on the implementation of efficiency strategies to improve care for adult patients presenting with chest pain.

IntroductionThis study evaluated the operational and clinical outcomes for patients presenting to an emergency department (ED) with chest pain using a 2-hour high-sensitivity troponin T (hs-TnT) protocol compared to an existing 3-hour hs-TnI protocol. MethodsThis retrospective cohort study used eight population-based linked health administrative datasets for adult patients presenting to a Canadian urban ED with chest pain over a two-year period. The primary outcome was ED length of stay (LOS). Secondary outcomes included health outcomes within 30 days. ResultsOverall, 5426 patients were included; 2879 and 2547 in the hs-TnI group and hs-TnT groups, respectively. The cohorts were similar: the median age was 58 years, 55% male, and comorbidities matched. Delays in physician initial assessment (PIA; +54 min; 95% CI: 42.2-65.8) and patients leaving without being seen increased (7% vs 12.5%; P &lt; 0.0001) due to worsening overcrowding. The median ED LOS increased from 448 to 481 minutes after hs-TnT implementation (median difference = 33.0; 95% CI: 19.9 to 46.1), although time to second tests decreased by 54 minutes. At 30 days, there were no differences in readmission or death before and after the intervention. ConclusionImplementation of a 2-hour hs-TnT protocol resulted in mixed outcomes: increased PIA and ED LOS, yet faster time to second test. The journey through the ED for patients with chest pain is complex and affected by issues beyond the assay type and the timing of repeat Tn measurements. ED overcrowding needs to be addressed for efficiency to be realized in this setting.

Significance of an Early Repeat Troponin Measurement Upon Presentation to the Hospital for Acute Heart Failure.

Higher cardiac troponin is associated with worse outcomes in patients with acute heart failure. The significance of repeat measurements over hours remains unclear. We assessed whether a repeat measurement and the Δ between measurements of high-sensitivity cardiac troponin I (hs-cTnI) were associated with outcomes in hypervolemic patients with acute heart failure without acute coronary syndrome. We analyzed 582 individuals from AKINESIS (Acute Kidney Injury Neutrophil Gelatinase-Associated Lipocalin Evaluation of Symptomatic Heart Failure Study) with hs-cTnI measured ≤12 hours from admission and repeated ≤6 hours thereafter. Associations between hs-cTnI levels and their Δ with short-term (death, intensive care unit admission, receipt of inotropes, or positive pressure ventilation during hospitalization) and long-term (death or heart failure readmission within 1 year) outcomes were assessed. The average age was 69±13 years, 62% were men, 65% were White, 46% had coronary artery disease, and 22% had chest pain. Median hs-cTnI levels were 27 (interquartile range [IQR], 13-62) ng/L initially and 28 (IQR, 14-68) ng/L subsequently, with a Δ of 0 [IQR, -2 to 4] ng/L over 3.4±1 hours. Only the second measurement was associated with short-term outcomes (odds ratio, 1.14 per 2-fold higher [95% CI, 1.02-1.28]). Both individual measurements and the Δ were associated with long-term outcomes (hazard ratios, 1.09, 1.12, and 1.16 for first, second, and Δ, respectively). Associated risk for the first and second measurements were not constant over the year but highest early after being measured and decreased over 1 year. Repeat measurements of hs-cTnI over hours can identify individuals with acute heart failure without acute coronary syndrome at risk for short- and long-term outcomes.

The Mayo ATTR-CM score versus other diagnostic scores and cardiac biomarkers in patients with suspected cardiac amyloidosis.

Several scores were developed to help the diagnosis of cardiac amyloidosis (CA). The most recent one, being the Mayo transthyretin amyloidosis cardiomyopathy (ATTR-CM) score, was not externally validated. We compared the diagnostic performance of the ATTR-CM score with previous tools (increased wall thickness [IWT] score, AMYLoidosis Index [AMYLI] score, and cardiac biomarkers) in a cohort of patients evaluated for a suspicion of CA. We analysed 362 consecutive patients referred to a third-level centre for suspected CA. Overall, 132 (36%) had transthyretin CA (ATTR-CA), and 91 (25%) immunoglobulin light chain CA (AL-CA); CA was excluded in 139 (38%). ATTR-CM score had a good diagnostic performance to distinguish ATTR-CA from AL-CA or no CA, with an area under the curve (AUC) of 0.795 (95% confidence interval [CI] 0.747-0.842, p < 0.001), and ATTR-CA from no CA (AUC 0.822, 95% CI 0.774-0.871, p < 0.001). Results were consistent in both patients with preserved (AUC 0.787, 95% CI 0.726-0.848, p < 0.001), and reduced or mildly reduced ejection fraction (AUC 0.790, 95% CI 0.709-0.871, p < 0.001). The ATTR-CM score showed a better discrimination compared to IWT and AMYLI score to distinguish ATTR-CA from AL-CA or no CA (p = 0.002), but not to distinguish ATTR-CA from no CA (p = 0.270). Diagnostic accuracy was significantly higher for the ATTR-CM score as compared to the rule-in cut-off of high-sensitivity troponin T. The Mayo ATTR-CM score has a good performance in identifying patients with ATTR-CA, with also better discrimination power when compared to other scores and biomarkers.

Correlation of greyzone fibrosis compared to troponin T and late gadolinium enhancement with survival and ejection fraction in patients after acute myocardial infarction.

To quantify greyzone fibrosis (GZF) in patients after acute myocardial infarction (MI) and to evaluate its correlation with MI-free survival and improvements in left ventricular ejection fraction (LVEF) compared with the established risk factors high-sensitivity cardiac troponin T (hs-cTnT) and Late Gadolinium Enhancement (LGE). The study involved 176 patients who experienced acute MI and underwent cardiac magnetic resonance (CMR) prior to hospital discharge, followed by a second CMR on average six months later. LGE was quantified in both examinations, a separate analysis of the GZF was conducted only in the follow-up CMR after resolution of the initial infarct edema. LVEF was measured in both CMR. hs-cTnT levels were assessed at hospital admission, as well as 8, 16, 24, 48 and 72h after coronary intervention. Telephone follow-ups were conducted annually for up to 8years. LGE measurements showed better correlation with MI-free survival (Harrell's C of 0.711 of LGE mass) compared to GZF (0.579 of GZF mass). Additionally, hs-cTnT outperformed GZF (Harrell's C of 0.645). As an univariable predictor for MI-free survival, only hs-cTnT reached significance (p < 0.05). With regard to improvements in ejection fraction, both hs-cTnT and LGE measurements showed acceptable correlation with improvement in ejection fraction (p < 0.05), while GZF measurements showed no correlation (p > 0.5). In CMR, the assessment of GZF demonstrated inferior p correlation compared to hs-cTnT and LGE in patients after acute MI with respect to the endpoint of MI-free survival. Furthermore, GZF showed no correlation with the improvement of LVEF.

Unexpected Grave’s-induced acute myocardial infarction in a young female, a literature review based on a case report

IntroductionMyocardial ischemia can occur due to several causes, which result in an imbalance between the supply and demand of oxygen to cardiac muscles. One potential reason for this condition is the overwork of the heart due to hyperstimulated thyroid function.Case presentationThe patient was a 36-year-old woman who presented with left-sided chest pain, dyspnea, palpitation, and tremor. The initial evaluation showed evidence of myocardial ischemia (positive high-sensitivity troponin) caused by a hyperactive thyroid gland. The treatment for myocardial infarction, along with anti-thyroid medications, improved the patient’s condition and subsided the symptoms. The coronary angiography revealed no pathologic finding, and the hypokinetic left ventricle, observed in the first echocardiogram, was resolved. The patient was discharged with an excellent clinical condition, and after the 4-month taking of a calcium channel blocker and tapering carbimazole, the thyroid function became normal, and her symptoms resolved completely.ConclusionPatients without evident risk factors for ischemic heart disease, such as non-diabetic, nonsmoker, and young individuals who presented with acute coronary syndrome, should be evaluated for a potential background reason for the imbalance between the oxygen demand and supply of the myocardium. The presence of palpitation, weight loss, tremors, insomnia, and anxiousness, along with ischemic signs, should make the physician think about the probability of the hyperthyroid-induced cardiovascular disorder.Clinical key pointThe initial presentation of hyperthyroidism might be accompanied by severe cardiac symptoms. When the demographic features are not aligned with usual ischemic heart disease, other probable symptoms and signs should be investigated, and thyroid function should be checked. The control of thyroid hyperactivity would result in the resolution of both cardiac and non-cardiac symptoms.

Association of cardiorenal biomarkers with mortality in metabolic syndrome patients: A prospective cohort study from NHANES.

Approximately 20%-25% of the global adult population is affected by metabolic syndrome (MetS), highlighting its status as a major public health concern. This study aims to investigate the predictive value of cardiorenal biomarkers on mortality among patients with MetS, thus optimizing treatment strategies. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) cycles between 1999 and 2004, we conducted a prospective cohort study involving 2369 participants diagnosed with MetS. We evaluated the association of cardiac and renal biomarkers with all-cause and cardiovascular disease (CVD) mortality, employing weighted Cox proportional hazards models. Furthermore, machine learning models were used to predict mortality outcomes based on these biomarkers. Among 2369 participants in the study cohort, over a median follow-up period of 17.1 years, 774 (32.67%) participants died, including 260 (10.98%) from CVD. The highest quartiles of cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP]) and renal biomarkers (beta-2 microglobulin, [β2M]) were significantly associated with increased risks of all-cause mortality (hazard ratios[HRs] ranging from 1.94 to 2.06) and CVD mortality (HRs up to 2.86), after adjusting for confounders. Additionally, a U-shaped association was observed between high-sensitivity cardiac troponin T (Hs-cTnT), creatinine (Cr), and all-cause mortality in patients with MetS. Machine learning analyses identified Hs-cTnT,NT-proBNP, and β2M as important predictors of mortality, with the CatBoost model showing superior performance (area under the curve[AUC] = 0.904). Cardiac and renal biomarkers are significant predictors of mortality in MetS patients, with Hs-cTnT, NT-proBNP, and β2M emerging as crucial indicators. Further research is needed to explore intervention strategies targeting these biomarkers to improve clinical outcomes.

Metabolic dysfunction and incidence of heart failure subtypes among Black individuals: The Jackson Heart Study.

The extent to which metabolic syndrome (MetS) severity influences subclinical myocardial remodelling, heart failure (HF) incidence and subtypes, remains unclear. We assessed the association of MetS with incident HF (including ejection fraction subtypes) among Black individuals. We included 4069 Jackson Heart Study participants (mean age 54.4 years, 63.8% women, 37.2% with MetS) without HF. We categorized participants based on MetS status and MetS severity scores (based on waist circumference [MetS-Z-WC] and body mass index [MetS-Z-BMI]). We assessed the associations of MetS indices with echocardiographic parameters, biomarkers of myocardial damage (high-sensitivity cardiac troponin I [hs-cTnI] and B-type natriuretic peptide [BNP]) and incident HF hospitalizations including HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). MetS severity was associated with subclinical cardiac remodelling (assessed by echocardiographic measures and biomarkers of myocardial damage). Over a median of 12 years, 319 participants developed HF (157 HFpEF, 149 HFrEF and 13 HF of unknown type). MetS was associated with a twofold greater risk of HF (hazard ratio [HR] 2.07, 95% confidence interval [CI] 1.64-2.61). Compared to the lowest quartile (Q1) of MetS-Z-WC, the highest quartile (Q4) conferred a higher risk of HF (HR 2.35, 95% CI 1.67-3.30), with a stronger association for HFpEF (Q4 vs. Q1: HR 4.94, 95% CI 2.67-9.14) vs. HFrEF (HR 1.69, 95% CI 1.06-2.70). Metabolic syndrome severity was associated with both HF subtypes among Black individuals, highlighting the importance of optimal metabolic health for preventing HF.

Sex-specific high-sensitivity troponin T cut-points have similar safety but lower efficacy than overall cut-points in a multisite U.S. cohort.

Data comparing the performance of sex-specific to overall (non-sex-specific) high-sensitivity cardiac troponin (hs-cTn) cut-points for diagnosing acute coronary syndrome (ACS) are limited. This study aims to compare the safety and efficacy of sex-specific versus overall 99th percentile high-sensitivity cardiac troponin T (hs-cTnT) cut-points. We conducted a secondary analysis of the STOP-CP cohort, which prospectively enrolled emergency department patients ≥ 21 years old with symptoms suggestive of ACS without ST-elevation on initial electrocardiogram across eight U.S. sites (January 25, 2017-September 6, 2018). Participants with both 0- and 1-h hs-cTnT measures less than or equal to the 99th percentile (sex-specific 22 ng/L for males, 14 ng/L for females; overall 19 ng/L) were classified into the rule-out group. The safety outcome was adjudicated cardiac death or myocardial infarction (MI) at 30 days. Efficacy was defined as the proportion classified to the rule-out group. McNemar's test and a generalized score statistic were used to compare rule-out and 30-day cardiac death or MI rates between strategies. Net reclassification improvement (NRI) index was used to further compare performance. This analysis included 1430 patients, of whom 45.8% (655/1430) were female; the mean ± SD age was 57.6 ± 12.8 years. At 30 days, cardiac death or MI occurred in 12.8% (183/1430). The rule-out rate was lower using sex-specific versus overall cut-points (70.6% [1010/1430] vs. 72.5% [1037/1430]; p = 0.003). Among rule-out patients, the 30-day cardiac death or MI rates were similar for sex-specific (2.4% [24/1010]) vs. overall (2.3% [24/1037]) strategies (p = 0.79). Among patients with cardiac death or MI, sex-specific versus overall cut-points correctly reclassified three females and incorrectly reclassified three males. The sex-specific strategy resulted in a net of 27 patients being incorrectly reclassified into the rule-in group. This led to an NRI of -2.2% (95% CI -5.1% to 0.8%). Sex-specific hs-cTnT cut-points resulted in fewer patients being ruled out without an improvement in safety compared to the overall cut-point strategy.

Heart Failure Risk Assessment Using Biomarkers in Patients With Atrial Fibrillation: Analysis From COMBINE-AF

BackgroundHeart failure (HF) is common among patients with atrial fibrillation (AF), and accurate risk assessment is clinically important. ObjectivesThe goal of this study was to investigate the incremental prognostic performance of N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and growth differentiation factor (GDF)-15 for HF risk stratification in patients with AF. MethodsIndividual patient data from 3 large randomized trials comparing direct oral anticoagulants (DOACs) with warfarin (ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis In Myocardial Infarction 48], and RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy]) from the COMBINE-AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) cohort were pooled; all patients with available biomarkers at baseline were included. The composite endpoint was hospitalization for HF (HHF) or cardiovascular death (CVD), and secondary endpoints were HHF and HF-related death. Cox regression was used, adjusting for clinical factors, and interbiomarker correlation was addressed using weighted quantile sum regression analysis. ResultsIn 32,041 patients, higher biomarker values were associated with a graded increase in absolute risk for CVD/HHF, HHF, and HF-related death. Adjusting for clinical variables and all biomarkers, NT-proBNP (HR per 1 SD: 1.68; 95% CI: 1.59-1.77), hs-cTnT (HR: 1.39; 95% CI: 1.33-1.44), and GDF-15 (HR: 1.20; 95% CI: 1.15-1.25) were significantly associated with CVD/HHF. The discrimination of the clinical model improved significantly upon addition of the biomarkers (c-index: 0.70 [95% CI: 0.69-0.71] to 0.77 [95% CI: 0.76-0.78]; likelihood ratio test, P < 0.001). Using weighted quantile sum regression analysis, the contribution to risk assessment was similar for NT-proBNP and hs-cTnT for CVD/HHF (38% and 41%, respectively); GDF-15 provided a statistically significant but lesser contribution to risk assessment. Results were similar for HHF and HF-related death, individually, and across key subgroups of patients based on a history of HF, AF pattern, and reduced or preserved left ventricular ejection fraction. ConclusionsNT-proBNP, hs-cTnT, and GDF-15 contributed significantly and independently to the risk stratification for HF endpoints in patients with AF, with hs-cTnT being as important as NT-proBNP for HF risk stratification. Our findings support a possible future use of these biomarkers to distinguish patients with AF at low or high risk for HF.

Evaluation of the analytical and clinical performance of a high-sensitivity troponin I point-of-care assay in the Mersey Acute Coronary Syndrome Rule Out Study (MACROS-2).

The objective of this study is to evaluate the analytical and diagnostic performance of a high-sensitivity point-of-care (POC) cardiac troponin I assay, the Quidel TriageTrue™ (QuidelOrtho Inc, San Diego, USA), compared to central laboratory testing (CLT) in accelerated diagnostic protocols (ADP) in real time in a clinical environment. In a nested sub-study of a pragmatic randomised control trial, consecutive patients with suspected acute coronary syndrome (ACS) and chest pain <12 h duration were randomised to the ESC 0/1 and 0/3-h ADP. Subjects underwent sampling for Quidel TriageTrue POC hs-TnI whole blood and plasma, CLT hs-TnT Roche Elecsys and a validated, NICE approved CLT High sensitivity cardiac troponin I (hs-TnI) (Siemens Attellica) at each time point. Assay imprecision was assessed by repeat analysis of whole blood samples at three levels (low, near 10 % CV 5-10 ng/L, medium, approximating 99th percentile 15-25 ng/L and high, 3-5 times the 99th percentile, 60-100 ng/L). Final diagnosis was adjudicated at 6weeks by Roche hs-TnT using the 4th universal definition of myocardial infarction (MI). A total of 1,157 patients consented and had both investigational POC whole blood and plasma and central lab hs-cTn available. The median age was 59, 47.2 % were female and 15 % had suffered a previous MI. Assay imprecision of whole blood POC TriageTrue revealed 10 % CV at 8.6 ng/L (>50 % lower than 99th percentile [20.5 ng/L]) and a 20 % CV at 1.2 ng/L. Receiver operator characteristics (ROC) curves were computed for each assay against adjudicated index type 1 MI to study clinical performance. At all-time points there were excellent performance for whole blood POC TriageTrue: area under the curve (AUC) 0.97 [95 % CI 0.94-098], 0.98 [95 % CI 0.97-1.00] and 0.95 [95 % CI 0.92-0.98] at time 0, 1 and 3 h respectively. There was statistical equivalence for performance of whole blood and plasma POC TriageTrue hs-TnI and laboratory Siemens Atellica hs-TnI. The whole blood POC TriageTrue hs-TnI assay demonstrates imprecision levels consistent with high sensitivity characteristics and has a clinical performance equivalent to an established, validated and NICE approved laboratory Siemens Atellica hs-TnI.