Clinical and Analytical Performance of a Novel Point-of-Care High-Sensitivity Cardiac Troponin I Assay.

BACKGROUND: Point-of-care (POC) high-sensitivity cardiac troponin assays may further accelerate the diagnosis of myocardial infarction (MI). OBJECTIVES: This study sought to assess the clinical and analytical performance of the novel high-sensitivity cardiac troponin I (hs-cTnI)-SPINCHIP POC test. METHODS: Adult patients presenting with acute chest discomfort to the emergency department were enrolled in an international, diagnostic, multicenter study. The final diagnosis was centrally adjudicated by 2 independent cardiologists using all clinical information. We compared the discriminatory performance of hs-cTnI-SPINCHIP with current established central laboratory assays and derived an assay-specific hs-cTnI-SPINCHIP 0/1-hour algorithm. Secondary analyses included sample type comparisons (whole blood, fresh/frozen plasma, and capillary finger prick) and precision analysis. RESULTS: MI was the adjudicated final diagnosis in 214 (19%) of 1,102 patients. Area under the receiver-operating characteristic curve was 0.94 (95% CI: 0.92-0.95) for hs-cTnI-SPINCHIP vs 0.94 (95% CI: 0.92-0.95) for hs-cTnI-Architect (P = 0.907) and 0.93 (95% CI: 0.91-0.95) for high-sensitivity cardiac troponin T Elecsys (P = 0.305). A cutoff <7 ng/L at presentation (if chest pain onset was >3 hours) or <7 ng/L together with a 0/1-hour delta of <4 ng/L ruled out 51% with a sensitivity and negative predictive value of 100% (95% CI: 97.7%-100%) and 100% (95% CI: 99.0%-100%), respectively. A hs-cTnI-SPINCHIP concentration ≥36 ng/L or a 0/1-hour delta ≥11 ng/L ruled in 27% with a specificity and positive predictive value of 90.9% (95% CI: 88.3%-92.9%) and 72.9% (95% CI: 66.4%-78.6%), respectively. Bootstrap internal validation confirmed excellent diagnostic performance. High agreement was observed between different sample types. CONCLUSIONS: The SPINCHIP hs-cTnI POC test has very high diagnostic accuracy. Its assay-specific 0/1-hour algorithm achieved very high sensitivity/negative predictive value and specificity/positive predictive value for rule-out/in MI. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study [APACE]; NCT00470587).

Sleep duration and cognitive function, The Akershus Cardiac Examination 1950 Study.

INTRODUCTION: Sleep duration are proposed as a lifestyle-related risk factor for cognitive impairment. We investigated the association between sleep duration and cognitive function in a large population-based cohort aged 62-65 years. METHODS: Cross-sectional analyses from the The Akershus Cardiac Examination 1950 Study. Linear and non-linear models were conducted to explore the association between self-reported sleep duration and cognitive function, adjusted for established risk factors for cognitive impairment. RESULTS: We included 3,348 participants, mean age (SD) was 63.9 ±0.6 years, 48.2% were women and 47.9% had education >12 years. Mean sleep duration (SD) was 7.0±1.0 hours, and 10.2% had abnormal sleep duration (<6 or >8 hours). Individuals reporting <6 hours or >8 hours of sleep scored significantly lower on MoCA test and Delayed recall trial in adjusted analysis. CONCLUSIONS: Sleep duration showed an inverted U-shaped association with global cognitive function and memory, suggesting that both shortened and prolonged sleep are related to adverse brain health.

Associations Between Biomarkers of Myocardial Injury and Systemic Inflammation and Risk of Incident Ventricular Arrhythmia.

BACKGROUND: Cardiac troponins (cTns) and biomarkers of inflammation are elevated in heart failure (HF) and predict cardiovascular risk. Whether these biomarkers associate with risk of ventricular arrhythmias (VAs) is unclear. OBJECTIVES: This study sought to assess whether cTnT, growth differentiation factor 15 (GDF-15), interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations are associated with incident VA. METHODS: In a prospective, observational study of patients treated with implantable cardioverter-defibrillator, cTnT, GDF-15, IL-6, and CRP were measured at baseline and after 1.4 ± 0.5 years and were associated with implantable cardioverter-defibrillator-detected incident VA, HF hospitalizations, and mortality. RESULTS: This study included 489 patients aged 66 ± 12 years and 83% were men. Median concentrations of cTnT were 15 (Q1-Q3: 9-25) ng/L at inclusion, and higher concentrations were associated with higher age, male sex, diabetes mellitus, coronary artery disease, and HF. During 3.1 ± 0.7 years of follow-up, 137 patients (28%) had ≥1 VA. cTnT concentrations were associated with an increased VA risk (per log-unit, HR: 1.63; 95% CI: 1.31-2.01; P < 0.001), also after adjustment for age, sex, body mass index, coronary artery disease, HF, renal function, and left ventricular ejection fraction (P < 0.001). GDF-15, IL-6, and CRP concentrations were not associated with incident VA, but all (including cTnT) were associated with HF hospitalization and mortality. Changes in cTnT, GDF-15, IL-6, and CRP from baseline to 1.4 years were not associated with subsequent VA. CONCLUSIONS: Higher concentrations of cTnT, GDF-15, IL-6, and CRP associate with HF hospitalization and death, but only cTnT predict incident VA. These findings suggest that myocardial injury rather than inflammation may play a pathophysiological role in VA and sudden cardiac death.

Left atrial function in middle-aged men and women with and without paroxysmal atrial fibrillation: Data from the Akershus Cardiac Examination (ACE) 1950 study.

PURPOSE: To assess left atrial (LA) function in individuals with known paroxysmal atrial fibrillation (AF) compared with healthy and nonhealthy individuals without atrial fibrillation. METHODS: The Akershus Cardiac Examination 1950 Study included 3,706 individuals all born in 1950. LA strain assessment of reservoir (LASr), conduit (LAScd) and contractile (LASct) functions were performed in all participants by investigators blinded to clinical data. Participants with cardiovascular disease, obesity, diabetes, pulmonary or renal disease were defined as nonhealthy, and those without as healthy. Patients with paroxysmal AF were identified through medical history and ECG documentation. RESULTS: LA strain assessment was feasible in 3,229 (87%) of the participants (50% women). The healthy group (n = 758) had significantly higher LASr and LAScd than the nonhealthy (n = 2,376), but LASct was similar between the groups. Participants with paroxysmal AF had significantly lower values of all strain parameters than the other groups. Multivariable logistic regression showed a significantly reduced probability of having AF per standard deviation increase in LASr and LASct. A nonlinear restricted cubic spline model fitted better with the association of LASr with paroxysmal AF than the linear model, and LA strain values below the population mean associated with an increased probability of having AF, but for values above the population mean no such association was present. CONCLUSION: Compared to participants without AF, those with known paroxysmal AF had significantly lower values of all LA strain parameters during sinus rhythm. Lower values of LA strain were associated with a significantly increased probability of having AF.

Systolic Blood Pressure, Diastolic Blood Pressure and Pulse Pressure and the Risk of Subclinical Myocardial Injury: The HUNT Study.

BACKGROUND: Subclinical myocardial injury expressed as higher cardiac troponin concentrations may represent an important intermediary between hypertension and the risk of cardiovascular disease. The study aimed to assess the relative strength of associations between systolic blood pressure (BP), diastolic BP, and pulse pressure, and subclinical myocardial injury, and how change in BP variables over time associates with subclinical myocardial injury. METHODS AND RESULTS: cTnl (cardiac troponin I) was measured in 32 968 participants of the fourth wave of the population-based cohort HUNT4 (Trøndelag Health Study) without a history of cardiovascular disease. An additional longitudinal analysis included participants from HUNT4 with BP measurements from HUNT3 (n=18 681). Associations between BP variables and cTnI concentrations were assessed by linear and logistic regression analyses. The median cTnI concentration was 1.6 ng/L (25th-75th percentiles, 0.6-3.1 ng/L), median age was 52 years (39.1-65.6 years), and 57% were female subjects. Cross-sectionally, only systolic BP categories ≥130 mm Hg associated with higher cTnI concentrations, compared with a reference systolic BP of <110 mm Hg. All categories of diastolic BP and pulse pressure were positively associated with higher cTnI concentrations when diastolic BP 70 to 79 mm Hg and pulse pressure <40 mm Hg were used as references, respectively. When comparing systolic BP, diastolic BP, and pulse pressure as continuous variables, cross-sectionally, pulse pressure most strongly associated with cTnI concentrations (P for all comparisons <0.001), whereas longitudinally, change in diastolic BP was most strongly associated with cTnI concentrations (P for all comparisons <0.05). CONCLUSIONS: Subjects with high pulse pressure and longitudinal increase in diastolic BP are at higher risk for subclinical myocardial injury.

Trans-Cardiac Gradient of Secretoneurin in Patients with Takotsubo Syndrome.

INTRODUCTION: Secretoneurin (SN) is a novel biomarker that provides prognostic information in patients with cardiovascular disease. In experimental models, SN production is increased in the failing myocardium. Currently, no information is available on SN production in human myocardium. Accordingly, we wanted to determine the trans-cardiac gradient of SN in patients with Takotsubo syndrome (TTS), and to correlate circulating SN concentrations with indices of cardiac structure and function. METHODS: We included 15 women diagnosed with TTS according to established criteria. Plasma SN concentrations were measured in blood samples obtained simultaneously from the aortic root and the coronary sinus. Coronary physiology was assessed by invasive measurements, and we used cardiac magnetic resonance imaging to determine left ventricular ejection fraction (LVEF) and cardiac mass. RESULTS: Median age was 65 years and median LVEF was 45%. Median SN concentration was 39 (25th-75th percentile 31-44) pmol/L in the coronary sinus and 37 (30-41) pmol/L in the aortic root (p = 0.02 for difference). SN concentrations in the aortic root showed the highest correlations with N-terminal B-type natriuretic peptide (rho = 0.47) and estimated glomerular filtration rate (rho = -0.41). In contrast, we found weak correlations between SN concentrations and index of myocardial resistance (rho = 0.12), LVEF (rho = 0.08), and cardiac mass (rho = -0.09). CONCLUSION: We demonstrate a positive trans-cardiac gradient of SN in patients with TTS, which supports the hypothesis that SN is produced and released in the human myocardium in situations of myocardial dysfunction and stress.

Reference intervals of circulating secretoneurin concentrations determined in a large cohort of community dwellers: the HUNT study.

OBJECTIVES: Secretoneurin (SN) is a novel cardiac biomarker that associates with the risk of mortality and dysfunctional cardiomyocyte Ca2+ handling in heart failure patients. Reference intervals for SN are unknown. METHODS: SN was measured with a CE-marked ELISA in healthy community dwellers from the fourth wave of the Trøndelag Health Study (HUNT4) conducted in 2017-2019. The common, sex and age specific 90th, 95th, 97.5th and 99th percentiles were calculated using the non-parametric method and outlier exclusion according to the Reed test. The applicability of sex and age specific reference intervals were investigated using Harris and Boyd test. We also estimated the percentiles in a subset with normal findings on echocardiographic screening. RESULTS: The total cohort included 887 persons (56.4 % women). After echocardiographic screening 122 persons were excluded, leaving a total of 765 persons (57.8 % women). The 97.5th percentile (95 % CI in brackets) of SN was 59.7 (57.5-62.1) pmol/L in the total population and 58.6 (57.1-62.1) pmol/L after echocardiography screening. In general, slightly higher percentiles were found in women and elderly participants, but less than 4 % in these subgroups had concentrations deviating from the common 97.5th percentile. Low BMI or eGFR was also associated with higher concentrations of SN. CONCLUSIONS: Upper reference limits for SN were similar amongst healthy adult community dwellers regardless of prescreening including cardiac echocardiography or not. Women and elderly showed higher concentrations of SN, but the differences were not sufficiently large to justify age and sex stratified upper reference limits.

Impact of the ESC Cardio-Oncology Guidelines Biomarker Criteria on Incidence of Cancer Therapy-Related Cardiac Dysfunction.

Background: The impact of recent consensus definitions of cancer therapy-related cardiac dysfunction (CTRCD) from the European Society of Cardiology cardio-oncology guidelines on the reported incidence of CTRCD has not yet been assessed. Objectives: The aim of this study was to assess the: 1) cumulative incidence; 2) point prevalence during and after adjuvant therapy; and 3) prognostic value of CTRCD as defined by different asymptomatic CTRCD guideline criteria. Methods: The cumulative incidence and point prevalence of CTRCD were retrospectively assessed in 118 patients participating in the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial. Asymptomatic CTRCD was assessed using alternative cardiac troponin (cTn) 99th percentile upper reference limits (URLs) to define cTnT and cTnI elevation. Results: The cumulative incidence of moderate or severe CTRCD was low (1.7%), whereas the cumulative incidence of mild asymptomatic CTRCD was higher and differed markedly according to the biomarker criteria applied, ranging from 49.2% of patients when cTnT greater than the sex-specific 99th percentile URL was used to define cTn elevation to 9.3% when sex-neutral cTnI was used. The point prevalence of CTRCD was highest at the end of anthracycline therapy (47.8%) and was driven primarily by asymptomatic cTn elevation. CTRCD during adjuvant therapy was not prognostic for CTRCD at extended follow-up of 24 months (Q1-Q3: 21-29 months) after randomization. Conclusions: Mild asymptomatic CTRCD during adjuvant breast cancer therapy was frequent and driven mainly by cTn elevation and was not prognostic of subsequent CTRCD. The incidence of mild, asymptomatic CTRCD differed markedly depending on the cTn assay and whether sex-neutral or sex-dependent URLs were applied. (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy [PRADA]; NCT01434134).

Carotid Plaque Score for Stroke and Cardiovascular Risk Prediction in a Middle-Aged Cohort From the General Population.

Background We aimed to explore the predictive value of the carotid plaque score, compared with the Systematic Coronary Risk Evaluation 2 (SCORE2) risk prediction algorithm, on incident ischemic stroke and major adverse cardiovascular events and establish a prognostic cutoff of the carotid plaque score. Methods and Results In the prospective ACE 1950 (Akershus Cardiac Examination 1950 study), carotid plaque score was calculated with ultrasonography at inclusion in 2012 to 2015. The largest plaque diameter in each extracranial segment of the carotid artery on both sides was scored from 0 to 3 points. The sum of points in all segments provided the carotid plaque score. The cohort was followed up by linkage to national registries for incident ischemic stroke and major adverse cardiovascular events (nonfatal ischemic stroke, nonfatal myocardial infarction, and cardiovascular death) throughout 2020. Carotid plaque score was available in 3650 (98.5%) participants, with mean±SD age of 63.9±0.64 years at inclusion. Only 462 (12.7%) participants were free of plaque, and and 970 (26.6%) had a carotid plaque score of >3. Carotid plaque score predicted ischemic stroke (hazard ratio [HR], 1.25 [95% CI, 1.15-1.36]) and major adverse cardiovascular events (HR, 1.21 [95% CI, 1.14-1.27]) after adjustment for SCORE2 and provided strong incremental prognostic information to SCORE2. The best cutoff value of carotid plaque score for ischemic stroke was >3, with positive predictive value of 2.5% and negative predictive value of 99.3%. Conclusions The carotid plaque score is a strong predictor of ischemic stroke and major adverse cardiovascular events, and it provides incremental prognostic information to SCORE2 for risk prediction. A cutoff score of >3 seems to be suitable to discriminate high-risk subjects. Registration Information clinicaltrials.gov. Identifier: NCT01555411.

Cardiac Troponin T and NT-proBNP for Prediction of 30-Day Readmission or Death in Patients with Acute Dyspnea: Data from the Akershus Cardiac Examination 2 Study.

INTRODUCTION: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) measurements are recommended in patients with acute dyspnea. We aimed to assess the prognostic merit of cTnT compared to NT-proBNP for 30-day readmission or death in patients hospitalized with acute dyspnea. METHODS: We measured cTnT and NT-proBNP within 24 h in 314 patients hospitalized with acute dyspnea and adjudicated the cause of the index admission. Time to first event of readmission or death ≤30 days after hospital discharge was recorded, and cTnT and NT-proBNP measurements were compared head-to-head. RESULTS: Patients who died (12/314) or were readmitted (71/314) within 30 days had higher cTnT concentrations (median: 32.6, Q1-Q3: 18.4-74.2 ng/L vs. median: 19.4, Q1-Q3: 8.4-36.1 ng/L; p for comparison <0.001) and NT-proBNP concentrations (median: 1,753.6, Q1-Q3: 464.2-6,862.0 ng/L vs. median 984, Q1-Q3 201-3,600 ng/L; for comparison p = 0.027) compared to patients who survived and were not readmitted. cTnT concentrations were associated with readmission or death within 30 days after discharge both in the total cohort (adjusted hazard ratio [aHR]: 1.64, 95% confidence interval [CI]: 1.30-2.05) and in patients with heart failure (HF) (aHR: 1.58, 95% CI: 1.14-2.18). In contrast, NT-proBNP concentrations were not associated with short-term events, neither in the total cohort (aHR: 1.10, 95% CI: 0.94-1.30) nor in patients with adjudicated HF (aHR: 1.06, 95% CI: 0.80-1.40). CONCLUSION: cTnT concentrations are associated with 30-day readmission or death in patients hospitalized with acute dyspnea, as well as in patients adjudicated HF.

Prognostic value of secretoneurin in chronic heart failure. Data from the GISSI-Heart Failure trial.

BACKGROUND: Circulating secretoneurin (SN) concentrations have been found to provide prognostic information in patients with acute heart failure. We wanted to assess whether SN would improve prognostication also in patients with chronic heart failure (HF) in a large multicenter trial. METHODS: We measured plasma SN concentrations at randomization (n = 1224) and after 3 months (n = 1103) in patients with chronic, stable HF from the GISSI-HF study. The co-primary endpoints were (1) time to death or (2) admission to hospital for cardiovascular reasons. RESULTS: Mean age was 67 years and 80% were male. Median (quartile 1-3) SN concentrations were 42.6 (35.0-62.8) pmol/L on randomization and 42.0 (34.5-53.1) pmol/L after 3 months, which are higher than SN concentrations in healthy subjects. Higher SN concentrations at randomization were associated with lower body-mass index (BMI), lower systolic blood pressure, lower estimated glomerular filtration rate (eGFR), higher B-type natriuretic peptide (BNP) concentrations, and diagnosis of chronic obstructive pulmonary disease. During median follow-up of 3.9 years, 344 patients (27.0%) died. After adjusting for age, sex, left ventricular ejection fraction, BMI, functional class, ischemic etiology, heart rate, blood pressure, eGFR, bilirubin, comorbidities, and BNP concentrations, logarithmically transformed SN concentrations on randomization were associated with mortality (HR 2.60 (95% CI 1.01-6.70), p = 0.047). SN concentrations were also associated with admission to hospital for cardiovascular reasons, but the association was attenuated and no longer significant in multivariable analysis. CONCLUSION: Plasma SN concentrations provided incremental prognostic information to established risk indices and biomarkers in a large cohort of chronic HF patients.

Associations between circulating microRNAs and lipid-rich coronary plaques measured with near-infrared spectroscopy.

Lipid-rich coronary atherosclerotic plaques often cause myocardial infarction (MI), and circulating biomarkers that reflect lipid content may predict risk of MI. We investigated the association between circulating microRNAs (miRs) are lipid-rich coronary plaques in 47 statin-treated patients (44 males) with stable coronary artery disease undergoing percutaneous coronary intervention. We assessed lipid content in non-culprit coronary artery lesions with near-infrared spectroscopy and selected the 4 mm segment with the highest measured lipid core burden index (maxLCBI4mm). Lipid-rich plaques were predefined as a lesion with maxLCBI4mm ≥ 324.7. We analyzed 177 circulating miRs with quantitative polymerase chain reaction in plasma samples. The associations between miRs and lipid-rich plaques were analyzed with elastic net. miR-133b was the miR most strongly associated with lipid-rich coronary plaques, with an estimated 18% increase in odds of lipid-rich plaques per unit increase in miR-133b. Assessing the uncertainty by bootstrapping, miR-133b was present in 82.6% of the resampled dataset. Inclusion of established cardiovascular risk factors did not attenuate the association. No evidence was found for an association between the other analyzed miRs and lipid-rich coronary plaques. Even though the evidence for an association was modest, miR-133b could be a potential biomarker of vulnerable coronary plaques and risk of future MI. However, the prognostic value and clinical relevance of miR-133b needs to be assessed in larger cohorts.

Patterns of Cardiac Troponin I Concentrations as Risk Predictors of Cardiovascular Disease and Death: The Trøndelag Health Study.

BACKGROUND: Concentrations of cardiac troponin predict risk of cardiovascular disease and death in the general population. There is limited evidence on changing patterns of cardiac troponin in the years preceding cardiovascular events. METHODS: We analyzed cardiac troponin I (cTnI) with a high-sensitivity assay in 3272 participants in the Trøndelag Health (HUNT) Study at study visit 4 (2017-2019). Of these, 3198 had measurement of cTnI at study visit 2 (1995-1997), 2661 at study visit 3, and 2587 at all 3 study visits. We assessed the trajectories of cTnI concentrations in the years prior to cardiovascular events using a generalized linear mixed model, with adjustment for age, sex, cardiovascular risk factors, and comorbidities. RESULTS: At HUNT4 baseline, median age was 64.8 (range 39.4-101.3) years, and 55% were women. Study participants who were admitted because of heart failure or died from cardiovascular cause on follow-up had a steeper increase in cTnI compared with study participants with no events (P < .001). The average yearly change in cTnI was 0.235 (95% confidence interval, 0.192-0.289) ng/L for study participants with heart failure or cardiovascular death, and -0.022 (95% confidence interval, -0.022 to -0.023) ng/L for study participants with no events. Study participants who experienced myocardial infarction, ischemic stroke, or noncardiovascular mortality exhibited similar cTnI patterns. CONCLUSIONS: Fatal and nonfatal cardiovascular events are preceded by slowly increasing concentrations of cardiac troponin, independently of established cardiovascular risk factors. Our results support the use of cTnI measurements to identify at-risk subjects who progress to subclinical and later overt cardiovascular disease.

Systolic blood pressure at age 40 and cognitive function 25 years later: the Akershus Cardiac Examination (ACE) 1950 Study.

OBJECTIVES: Hypertension in midlife is a risk factor for cognitive impairment. Still, the ideal midlife blood pressure (BP) remains unknown. We examined associations between different systolic blood pressure (SBP) levels at the age of 40-43 years and change in SBP over a 25-year period with cognitive function at age 62-65 years. METHODS: We included 2424 individuals born in 1950 who had participated both in the Age 40 Program (1990-1993) and the Akershus Cardiac Examination (ACE) 1950 Study (2012-2015). The exposure was SBP at age 40-43 years and the outcome was cognitive function at age 62-65 years, assessed with Montreal Cognitive Assessment, Delayed recall trial from the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Task, and Trail Making Test part B (TMT B). RESULTS: Participants were 40.1 ±â€Š0.3 years old with mean SPB 128 ±â€Š13 mmHg at the Age 40 Program, and 63.9 ±â€Š0.6 years old with mean SPB 138 ±â€Š18 at the ACE 1950 Study. Adjusted linear regressions showed no associations between SBP and subsequent cognitive function. In logistic regressions, individuals with SBP ≥140 mmHg, compared to individuals with SBP <120 mmHg (odds ratio 2.29, 95% confidence interval 1.28-4.10, P-value 0.005) had increased risk of an abnormal TMT B-score. Change in SBP during the 25-year follow-up was not associated with cognitive function. CONCLUSIONS: SBP ≥140 mmHg at age 40-43 was associated with reduced capacity on TMT B, a domain specific cognitive test sensitive to vascular impairment. No other associations were found between SBP, or change in SBP, and cognitive function.

Serial blood pressure measurements, left ventricular remodelling and cardiovascular outcomes.

BACKGROUND: Hypertension is a risk factor for the development of cardiovascular disease. Whether serial blood pressure (BP) measurements are more closely associated with subclinical left ventricular (LV) remodelling and better predict risk of cardiovascular events over individual BP measurements are not known. METHODS: We assessed systolic BP, diastolic BP and pulse pressure at several time points during adulthood in 1333 women and 1211 men participating in the Akershus Cardiac Examination 1950 Study. We defined serial BP measurements as the sum of averaged BPs from adjacent consecutive visits indexed to total exposure time between measurements. We assessed the associations between serial and individual BP measurements and (1) LV structure, function and volumes and (2) incident myocardial infarction, ischemic stroke, heart failure and cardiovascular death. RESULTS: All indices of higher serial BP measurements were associated with increased indexed LV mass, and the associations were stronger than those of individual BP measurements. Serial diastolic BP pressure was strongly and inversely associated with LV systolic function, while higher serial systolic BP was primarily associated with higher LV volumes. Both serial systolic (incidence rate ratio [IRR] 1.10, 95% CI 1.03 to 1.17) and diastolic BPs (IRR 1.14, 95% CI 1.02 to 1.27) were associated with increased incidence of clinical events. CONCLUSION: In healthy community dwellers without established cardiovascular disease, different serial BP indices associate strongly with LV remodelling and cardiovascular outcomes. Whether the use of serial BP indices for guiding treatment is superior to individual measurements should be explored in additional prospective studies.

Prediction of incident atrial fibrillation with cardiac biomarkers and left atrial volumes.

OBJECTIVE: Atrial fibrillation is a common arrhythmia associated with risk of stroke, heart failure and death. We aimed to elucidate the associations of cardiac biomarkers, echocardiographic left atrial volumetric indices and risk of prevalent and incident atrial fibrillation in the general population. METHODS: We assessed cardiac troponin T (cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), maximum (LAVimax) and minimum (LAVimin) indexed left atrial volumes and left atrial emptying fraction (LAEF) in subjects born in 1950 participating in the prospective observational cohort, Akershus Cardiac Examination 1950 Study. The Cohorts for Heart and Ageing Research in Genomic Epidemiology for Atrial Fibrillation risk score and sex was used to adjust for residual risk of atrial fibrillation. RESULTS: Out of 3487 subjects, 157 (4.5%) had prevalent and 123 (3.5%) had incident atrial fibrillation. Echocardiographic left atrial volumes and cardiac biomarkers associated with prevalent atrial fibrillation, but GDF-15 was non-significant in adjusted analysis. Incident atrial fibrillation was predicted by LAVimax (adjusted HR 1.51, 95% CI 1.30 to 1.75), LAVimin (adjusted HR 1.52, 95% CI 1.35 to 1.72), LAEF (adjusted HR 1.24, 95% CI 1.04 to 1.48) and NT-proBNP (adjusted HR 1.57, 95% CI 1.32 to 1.85). cTnT and NT-proBNP provided incremental prognostic information to left atrial volumes, but GDF-15 demonstrated no prognostic value for incident atrial fibrillation. CONCLUSIONS: In the general population, echocardiographic left atrial volumetric indices and NT-proBNP, but not cTnT and GDF-15, associate with prevalent atrial fibrillation and with risk of incident atrial fibrillation. cTnT and NT-proBNP provide incremental prognostic information to echocardiography.

The prevalence of cardiac complications and their impact on outcomes in patients with non-traumatic subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a serious condition, and a myocardial injury or dysfunction could contribute to the outcome. We assessed the prevalence and prognostic impact of cardiac involvement in a cohort with SAH. This is a prospective observational multicenter study. We included 192 patients treated for non-traumatic subarachnoid hemorrhage. We performed ECG recordings, echocardiographic examinations, and blood sampling within 24 h of admission and on days 3 and 7 and at 90 days. The primary endpoint was the evidence of cardiac involvement at 90 days, and the secondary endpoint was to examine the prevalence of a myocardial injury or dysfunction. The median age was 54.5 (interquartile range [IQR] 48.0-64.0) years, 44.3% were male and the median World Federation of Neurological Surgeons (WFNS) score was 2 (IQR 1-4). At day 90, 22/125 patients (17.6%) had left ventricular ejection fractions ≤ 50%, and 2/121 patients (1.7%) had evidence of a diastolic dysfunction as defined by mitral peak E-wave velocity by peak e' velocity (E/e') > 14. There was no prognostic impact from echocardiographic evidence of cardiac complications on neurological outcomes. The overall prevalence of cardiac dysfunction was modest. We found no demographic or SAH-related factors associated with 90 days cardiac dysfunction.

Associations between cardiovascular risk factors, biomarkers, and left ventricular mechanical dispersion: insights from the ACE 1950 Study.

Aims: Mechanical dispersion measures left ventricular contraction heterogeneity and is associated with the risk of sudden cardiac death. However, the associations between mechanical dispersion and cardiovascular risk factors in early mid-life, and established biomarkers of sub-clinical myocardial injury and dysfunction are not known. We aimed to examine this in the general population. Methods and results: During 2012-15, we included 2527 Norwegian individuals from the general population born in 1950, with measurements of mechanical dispersion by 2D speckle tracking echocardiography and concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) available. Mechanical dispersion was calculated as the standard deviation of the contraction duration of 17 strain segments. We assessed the associations between mechanical dispersion, concentrations of hs-cTnT and NT-proBNP, and cardiovascular risk factors collected at a national health screening survey two decades earlier. At echocardiography baseline, median age was 64 (interquartile range 63.5-64.5) years, 49.8% were women, 59.1% had hypertension, and 5.9% reported established coronary artery disease. Median mechanical dispersion was 38.0 (29.5-47.0) ms, median hs-cTnT concentration 6 (4-8) ng/L, and the median NT-proBNP concentration 54 (34-93) ng/L. Mechanical dispersion was associated with both hs-cTnT and NT-proBNP concentrations in multivariable models adjusted for clinical and echocardiographic variables. High body mass index, serum triglyceride concentrations, and low resting heart rate at Age 40 were independently associated with increased mechanical dispersion two decades later. Conclusion: Established risk factors at Age 40 are associated with mechanical dispersion two decades later, and mechanical dispersion is cross-sectionally associated with biomarkers of subclinical myocardial injury and dysfunction.

QRS fragmentation is associated with increased risk of ventricular arrhythmias in high-risk patients; Data from the SMASH 1 Study.

INTRODUCTION: QRS fragmentation (fQRS), defined as the presence of additional spikes within the QRS complex, has been associated with myocardial conduction abnormalities and arrhythmogenicity. OBJECTIVE: We aimed to assess whether fQRS is associated with incident ventricular arrhythmias (VA) in high-risk patients treated with implantable cardioverter-defibrillator (ICD) for primary and secondary prevention. METHODS: In a prospective observational multicenter study, we included 495 patients treated with ICD. fQRS was analyzed according to previously validated criteria, by two physicians blinded for outcome data. Incident VA were obtained from ICD recordings. RESULTS: ECG recordings interpretable for fQRS were available in 459 patients (93%), aged 66 ± 12 years with left ventricular ejection fraction 40% ± 13%. fQRS was present in 52 patients (11%) with comparable baseline characteristics to patients without fQRS, except higher age, higher prevalence of coronary artery disease (CAD), lower prevalence of cardiomyopathy, and more frequently a secondary prevention ICD indication. Among patients with native QRS, those with fQRS had similar QRS duration and axis to those without fQRS. During 3.1 ± 0.7 years follow-up, 126 patients (28%) had ≥1 VA . fQRS was associated with increased risk of VA (HR 3.41 [95% CI 2.27-5.13], p < .001), which persisted after adjusting for age, gender, sex, BMI, CAD, heart failure, renal function, ICD indication, QRS duration, QRS axis, Q waves, and bundle branch block. fQRS was more strongly associated with VA in patients with a primary (HR 6.05 [95% CI 3.16-11.60]) versus secondary (HR 2.39 [95% CI 1.41-4.04]) ICD indication (p-for-interaction = .047). CONCLUSIONS: fQRS is associated with threefold increased risk of VA in high-risk patients, independent of established risk factors.