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Pivotal trials of beta-blockers (BB) and angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in acute myocardial infarction (AMI) were largely conducted prior to the widespread adoption of early revascularization. A total of 15,073 patients with AMI who underwent inhospital coronary revascularization from January 2007 to December 2013 were analyzed. At 12 months, BB was significantly associated with a lower incidence of major adverse cardiovascular events (MACE, adjusted HR 0.80, 95% CI 0.70–0.93) and all-cause mortality (adjusted HR 0.69, 95% CI 0.55–0.88), while ACEI/ARB was significantly associated with lower all-cause mortality (adjusted HR 0.80, 95% CI 0.66–0.98) and heart failure (HF) hospitalization (adjusted HR 0.80, 95% CI 0.68–0.95). Combined BB and ACEI/ARB use was associated with the lowest incidence of MACE (adjusted HR 0.70, 95% CI 0.57–0.86), all-cause mortality (adjusted HR 0.55, 95% CI 0.40–0.77) and HF hospitalization (adjusted HR 0.64, 95% CI 0.48–0.86). This were consistent for left ventricular ejection fraction

BACKGROUND Myocardial infarction (MI) is a high-risk condition especially when filling pressure is raised, and earlier reports have suggested that E/e' is associated with poor outcome. However, whether E/e' predicts risk better than LVEF, which is the current standard of practice, is not known. We investigated this question in the largest and most rigorous study of MI patients so far. METHODS AND RESULTS We studied 660 patients with ST-elevation MI (STEMI) treated with primary percutaneous coronary intervention and related E/e' to short-term mortality (in-hospital death), as well as long-term events at 2 years comprising (a) a composite of MI, stroke, heart failure, and death, and (b) death alone. Short-term models were adjusted for age, sex, and LVEF. Long-term models were adjusted for age, sex, diabetes, revascularization procedure, history of MI, hypertension, renal function, drugs on discharge, and LVEF. Elevated E/e'> 15 indicated higher risk of short-term events (n = 19:7.0% (95% confidence interval 3.4-10.8%) vs. 1.0% (0.3 - 2.3%); adjusted odds ratio 3.7 (1.3-10.5)). While elevated E/e' was also associated with long-term outcomes (n = 103 composite events: 15.9% (11.9% - 21.4%) vs 6.8% (5.2% - 8.7%), P

Background: Real world data on clinical outcomes and quality of care for patients with coronary artery disease (CAD) are fragmented. We describe the rationale and design of the Singapore Cardiovascular Longitudinal Outcomes Database (SingCLOUD). Methods and Results: We designed a health data grid to integrate clinical, administrative, laboratory, procedural, prescription and financial data from all public-funded hospitals and primary care clinics, which provide 80% of health care in Singapore. Here, we explain our approach to harmonize real-world data from diverse electronic medical and non-medical platforms to develop a robust and longitudinal dataset. We present pilot data on patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) between 2012 and 2014. The initial data set had 53,395 patients. Of these, 35,203 had CAD confirmed on coronary angiography, of whom 21,521 had PCI. Eventually, limiting to 2012-2014, 3,819 patients had MI with PCI, while 5,989 had MI. Compared with the quality improvement registry, Singapore Cardiac Data Bank, which had 189 fields for analysis, the SingCLOUD platform generated an additional 313 additional data fields, and was able to identify an additional 250 heart failure events, 664 major adverse cardiovascular events at 2 years, and low-density lipoprotein levels to 1 year for 3,747 patients. Conclusions: By integrating multiple incongruent data sources, SINGCLOUD enables in-depth analysis of real-world cardiovascular "big data".

We aimed to identify independent predictors of cardiac mortality and hospitalization for heart failure (HHF) from a real-world, multi-ethnic Asian registry [the Singapore Myocardial Infarction Registry] of ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention. 11,546 eligible STEMI patients between 2008 and 2015 were identified. In-hospital, 30-day and 1-year cardiac mortality and 1-year HHF rates were 6.4%, 6.8%, 8.3% and 5.2%, respectively. From the derivation cohort (70% of patients), age, Killip class and cardiac arrest, creatinine, hemoglobin and troponin on admission and left ventricular ejection fraction (LVEF) during hospitalization were predictors of in-hospital, 30-day and 1-year cardiac mortality. Previous ischemic heart disease (IHD) was a predictor of in-hospital and 30-day cardiac mortality only, whereas diabetes was a predictor of 1-year cardiac mortality only. Age, previous IHD and diabetes, Killip class, creatinine, hemoglobin and troponin on admission, symptom-to-balloon-time and LVEF were predictors of 1-year HHF. The c-statistics were 0.921, 0.901, 0.881, 0.869, respectively. Applying these models to the validation cohort (30% of patients) showed good fit and discrimination (c-statistic 0.922, 0.913, 0.903 and 0.855 respectively; misclassification rate 14.0%, 14.7%, 16.2% and 24.0% respectively). These predictors could be incorporated into specific risk scores to stratify reperfused STEMI patients by their risk level for targeted intervention.

It is unclear whether universal access to primary percutaneous coronary intervention (pPCI) may reduce sex differences in 1-year rehospitalization for heart failure (HF) and myocardial infarction (MI) after ST-elevation myocardial infarction (STEMI). We studied 7,597 consecutive STEMI patients (13.8% women, n = 1,045) who underwent pPCI from January 2007 to December 2013. Cox regression models adjusted for competing risk from death were used to assess sex differences in rehospitalization for HF and MI within 1 year from discharge. Compared with men, women were older (median age 67.6 vs 56.0 years, p0.001) with higher prevalence of co-morbidities and multivessel disease. Women had longer median door-to-balloon time (76 vs 66 minutes, p0.001) and were less likely to receive drug-eluting stents (19.5% vs 24.1%, p = 0.001). Of the medications prescribed at discharge, fewer women received aspirin (95.8% vs 97.6%, p = 0.002) and P2Y

Clinical guidelines recommend that the exercise protocol of a stress echocardiogram is selected to induce volitional exhaustion after a target duration of at least 8 minutes. While the Bruce protocol is very commonly used for clinical stress tests, it is known to be "steep", and many patients therefore fail to reach 8 minutes. We studied predictors of failure and developed a method for identifying patients not suitable for Bruce protocol which was accurate and yet simple enough to be used as a point-of-care decision support tool.We studied data out-patients undergoing Bruce protocol stress echocardiograms (n = 11 086) and analyzed predictors of inappropriate early termination (defined as test duration 8 min as per current practice guidelines) using logistic regression. A prediction model was constructed as follows: .5 points were given for each of hypertension, diabetes, smoking, and E/e' 7.9 in the resting echocardiogram; .1 point was added for each 1-unit increment in body mass index; 1 point was added for patient age by decade; 2.0 points were subtracted for male sex (p for all 0.001). In tests on held-out validation data, the model was well calibrated (in plots of predicted vs actual risk) and discriminated failure versus non-failure well (C-statistic .86 for a score of 6.0 points; p 0.001).These data may help to standardize protocol selection in stress echocardiography, by identifying patients pre-hoc where Bruce protocol will be inappropriately steep.

AIMS We aimed to identify a 'frequent admitter' phenotype among patients admitted for acute decompensated heart failure (HF). METHODS AND RESULTS We studied 10 363 patients in a population-based prospective HF registry (2008-2012), segregated into clusters based on their 3-year HF readmission frequency trajectories. Using receiver-operating characteristic analysis, we identified the index year readmission frequency threshold that most accurately predicts HF admission frequency clusters. Two clusters of HF patients were identified: a high frequency cluster (90.9%, mean 2.35 ± 3.68 admissions/year) and a low frequency cluster (9.1%, mean 0.50 ± 0.81 admission/year). An index year threshold of two admissions was optimal for distinguishing between clusters. Based on this threshold, 'frequent admitters', defined as patients with ≥ 2 HF admissions in the index year (n = 2587), were of younger age (68 ± 13 vs 69 ± 13 years), more often male (58% vs. 54%), smokers (38.4% vs. 34.4%) and had lower left ventricular ejection fraction (37 ± 17 vs. 41 ± 17%) compared to 'non-frequent admitters' (

Background Cardiac size measurements require indexing to body size. Allometric indexing has been investigated in Caucasian populations but a range of different values for the so-called allometric power exponent (b) have been proposed, with uncertainty as to whether allometry offers clinical utility above body surface area (BSA)-based indexing. We derived optimal values for b in normal echocardiograms and validated them externally in cardiac patients. Methods and results Values for b were derived in healthy adult Chinese males (n=1,541), with optimal b for left ventricular mass (LVM) of 1.66 (95% confidence interval 1.41-1.92). LV hypertrophy (LVH) defined as indexed LVM >75 g/m1.66 was associated with adverse outcomes in an external validation cohort (n=738) of patients with acute coronary syndrome (odds ratio for reinfarction: 2.4 (1.1-5.4)). In contrast, LVH defined by BSA-based indexing or allometry using exponent 2.7 exhibited no significant association with outcomes (P=NS for both). Cardiac longitudinal function also varied with body size: septal and RV free wall s', TAPSE and lateral e' all scaled allometrically (b=0.3-0.9). Conclusions An optimal b of 1.66 for LVM in healthy Chinese was found to validate well, with superior clinical utility both to that of BSA-based indexing and to b=2.7. The effect of allometric indexing of cardiac function requires further study.

Sleep is associated with various health outcomes. Despite their growing adoption, the potential for consumer wearables to contribute sleep metrics to sleep-related biomedical research remains largely uncharacterized. Here we analyzed sleep tracking data, along with questionnaire responses and multi-modal phenotypic data generated from 482 normal volunteers. First, we compared wearable-derived and self-reported sleep metrics, particularly total sleep time (TST) and sleep efficiency (SE). We then identified demographic, socioeconomic and lifestyle factors associated with wearable-derived TST; they included age, gender, occupation and alcohol consumption. Multi-modal phenotypic data analysis showed that wearable-derived TST and SE were associated with cardiovascular disease risk markers such as body mass index and waist circumference, whereas self-reported measures were not. Using wearable-derived TST, we showed that insufficient sleep was associated with premature telomere attrition. Our study highlights the potential for sleep metrics from consumer wearables to provide novel insights into data generated from population cohort studies., Jing Xian Teo et al. used sleep tracking data from consumer wearables, together with phenotypic data from 482 volunteers to identify factors associated with habitual sleep duration and sleep efficiency. They identified sleep metrics associated with cardiovascular disease risk markers, such as body mass index, and linked insufficient sleep to premature telomere shortening, a biomarker of aging.

Aims Ticagrelor reduces ischaemic events and mortality in acute coronary syndrome (ACS) vs. clopidogrel. We wished to study clinical outcomes in a large real-world population post-ACS. Methods and results We performed a prospective cohort study in 45 073 ACS patients enrolled into Swedish Web system for Enhancement and Development of Evidence-based care in Heart Disease Evaluated According to Recommended Therapies who were discharged on ticagrelor ( N = 11 954) or clopidogrel ( N = 33 119) between 1 January 2010 and 31 December 2013. The primary outcome was a composite of all-cause death, re-admission with myocardial infarction (MI) or stroke, secondary outcomes as the individual components of the primary outcome, and re-admission with bleeding. The risk of the primary outcome with ticagrelor vs. clopidogrel was 11.7 vs. 22.3% (adjusted hazard ratio (HR) 0.85 [95% confidence interval: 0.78–0.93]), risk of death 5.8 vs. 12.9% (adjusted HR 0.83 [0.75–0.92]), and risk of MI 6.1 vs. 10.8% (adjusted HR 0.89 [0.78–1.01]) at 24 months. Re-admission with bleeding with ticagrelor vs. clopidogrel occurred in 5.5 vs. 5.2% (adjusted HR 1.20 [1.04–1.40]). In a subset of patients undergoing percutaneous coronary intervention (PCI) on ticagrelor vs. clopidogrel the PCI-related in-hospital bleeding was 3.7 vs. 2.7% (adjusted odds ratio, OR, 1.57 [1.30–1.90]). Conclusion Ticagrelor vs. clopidogrel post-ACS was associated with a lower risk of death, MI, or stroke, as well as death alone. Risk of bleeding was higher with ticagrelor. These real-world outcomes are consistent with randomized trial results.

Perioperative myocardial damage and infarction (MI) is associated with increased mortality and other postoperative complications.To assess the incidence of perioperative myocardial damage in patients undergoing major elective noncardiac surgery, to elucidate any association with postoperative MI and mortality and to estimate the impact of preoperative risk factors and intraoperative hypotension.Observational cohort study.Karolinska University Hospital, Stockholm, Sweden, from October 2012 to May 2013.In this single-centre study, all adult patients undergoing major elective noncardiac surgery who were scheduled for an overnight admission to the postoperative unit were included. Patients undergoing phaeochromocytoma surgery were excluded. Preoperative risk factors (co-morbidities), intraoperative events (hypotension defined as a 50% decrease in SBP relative to each patient's baseline and lasting5 min) and postoperative data were collected from medical records. Levels of high-sensitivity cardiac troponin T (hs-cTnT) were measured on postoperative day 1. Myocardial damage was defined as an increase in the hs-cTnT value above 14 ng l. A cardiologist reviewed all cases of MI occurring within 30 days after surgery.Myocardial damage, MI and mortality within 30 days after surgery.Of the final cohort of 300 patients, 90 (30%) had myocardial damage on postoperative day 1 and 15 (5%) developed postoperative MI within 30 days. Multivariate logistic regression analysis demonstrated that an intraoperative reduction in SBP more than 50% from baseline lasting more than 5 min was an independent predictor of postoperative hs-cTnT elevation (odds ratio, 4.4; 95% confidence interval, 1.8 to 11.1).In a cohort of 300 patients undergoing major elective noncardiac surgery, there was a high incidence of myocardial damage and an association between an intraoperative reduction in SBP more than 50% from baseline lasting more than 5 min and myocardial damage.

The left ventricle (LV) ejects blood into the proximal aorta. Age and hypertension are associated with stiffening and dilation of the aortic root, typically viewed as indicative of adverse remodeling. Based on analytical considerations, we hypothesized that a larger aortic root should be associated with lower global afterload (effective arterial elastance, EA) and larger stroke volume (SV). Moreover, as antihypertensive drugs differ in their effect on central blood pressure, we examined the role of antihypertensive drugs for the relation between aortic root size and afterload. We studied a large group of patients (n = 1250; 61 ± 12 years; 78 % males; 64 % hypertensives) from a single-center registry with known or suspected coronary artery disease. Aortic root size was measured by echocardiography as the diameter of the tubular portion of the ascending aorta. LV outflow tract Doppler was used to record SV. In the population as a whole, after adjusting for key covariates in separate regression models, aortic root size was an independent determinant of both SV and EA. This association was found to be heterogeneous and stronger in patients taking a calcium channel blocker (CCB; 10.6 % of entire population; aortic root size accounted for 8 % of the explained variance of EA). Larger aortic root size is an independent determinant of EA and SV. This association was heterogeneous and stronger in patients on CCB therapy.

Despite growing adoption of consumer wearables, the potential for sleep metrics from these devices to contribute to sleep-related biomedical research remains largely uncharacterized. Here we analyze sleep tracking data, along with questionnaire responses and multi-modal phenotypic data, generated from 482 normal volunteers. First, we provide a detailed comparison of wearable-derived and self-reported sleep metrics, particularly total sleep time (TST) and sleep efficiency (SE). We then identified demographic, socioeconomic and lifestyle factors associated with wearable-derived sleep duration. We also analyzed our multi-modal phenotypic data and showed that wearable-derived TST and SE are associated with various cardiovascular disease risk markers, whereas self-reported measures were not. Using whole-genome sequencing data, we estimated leukocyte telomere length and showed that volunteers with insufficient sleep also exhibit premature telomere attrition. Our study highlights the potential for sleep metrics generated by consumer wearables to provide novel insights into data generated from population cohort studies.

Importance: Whether certain weather conditions modulate the onset of myocardial infarction (MI) is of great interest to clinicians because it could be used to prevent MIs as well as guide allocation of health care resources. Objective: To determine if weather is associated with day-to-day incidence of MI. Design, Setting, and Participants: In this prospective, population-based and nationwide setting, daily weather data from the Swedish Meteorological and Hydrological Institute were extracted for all MIs reported to the Swedish nationwide coronary care unit registry, Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART), during 1998 to 2013 and then merged with each MI on date of symptom onset and coronary care unit. All patients admitted to any coronary care unit in Sweden owing to MI were included. A total of 280 873 patients were included, of whom 92 044 were diagnosed as having ST-elevation MI. Weather data were available for 274 029 patients (97.6%), which composed the final study population. Data were analyzed between February 2017 and April 2018. Exposures: The nationwide daily mean air temperature, minimum air temperature, maximum air temperature, wind velocity, sunshine duration, atmospheric air pressure, air humidity, snow precipitation, rain precipitation, and change in air temperature. Main Outcomes amd Measures: The nationwide daily counts of MI as outcome. Results: In 274029 patients, mean (SD) age was 71.7 (12) years. Incidence of MI increased with lower air temperature, lower atmospheric air pressure, higher wind velocity, and shorter sunshine duration. The most pronounced association was observed for air temperature, where a 1-SD increase in air temperature (7.4°C) was associated with a 2.8% reduction in risk of MI (unadjusted incidence ratio, 0.972; 95% CI, 0.967-0.977; P

Objective Studies have related air pollution to myocardial infarction (MI) events over days or weeks, with few data on very short-term risks. We studied risk of ST-segment elevation MI (STEMI) within hours of exposure to air pollution while adjusting for weather. Methods We performed a case-crossover study of STEMI cases in Stockholm, Sweden (Jan 2000–June 2014) based on SWEDEHEART. Exposures during hazard periods up to 24 h prior to admission were compared to bidirectionally sampled control periods. Risks attributable to sulphur dioxide (SO2), nitrogen dioxide (NO2), ozone and particulate pollutants (PM2.5, PM10) were studied in conditional logistic regression models for interquartile range increments. Results Risk of STEMI (n = 14,601) was associated with NO2 (strongest at 15-h lag) and with PM2.5 (strongest at 20-h lag), in single-pollutant models adjusting for air temperature and humidity (NO2: odds ratio (OR; 95% confidence interval) 1.065 (1.031–1.101); PM2.5: 1.026 (1.001–1.054)). After adjusting models for atmospheric pressure (significantly associated with STEMI risk at 14–24-h lags), NO2 remained highly statistically significant (1.057 (1.022–1.094)) but not PM2.5 (1.024 (0.997–1.052)). No associations were seen for SO2, ozone or PM10. Conclusion Risk of STEMI rises within hours of exposure to air pollutants, with strongest impact of NO2. These findings are complementary to earlier reports which have not acknowledged widely the importance of very short-term fluctuations in air pollution.

The platelet inhibitor ticagrelor is strongly recommended during 12 months post-acute coronary syndrome (ACS) in European guidelines. We analysed clinical characteristics of patients given ticagrelor for ACS in the real world. We studied the use of ticagrelor in patients admitted for ACS in Sweden between 1 January 2012 and 31 December 2013 who were enrolled in the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART). Clinical characteristics were investigated for patients prescribed ticagrelor at discharge as well as for patients undergoing percutaneous coronary intervention who were prescribed ticagrelor. Independent factors associated with selecting ticagrelor were analysed in logistic regression. We found that 44.0% (n = 12 601) out of a total of 28 639 patients had been prescribed ticagrelor at discharge. After adjusting for age and sex, prior cardiovascular disease was less common in patients discharged on ticagrelor (myocardial infarction, ischaemic stroke, and peripheral vascular disease; P for all < 0.001). The risk of death as predicted by GRACE score and the risk of major bleeding as predicted by CRUSADE score were both lower in ticagrelor-treated patients vs. others (median 99 vs. 126 and median 23 vs. 25, respectively; P for both < 0.001). The intended treatment duration at discharge was 12 months in 82.5% of patients and < 12 months in 9.3%. Ticagrelor is preferentially being used in patients at lower risk. A minority of patients are recommended ticagrelor during < 12 months.

KEY POINTS A hallmark of mitral stenosis (MS) is the markedly altered left ventricular (LV) loading. As most of the methods used to determine LV performance in MS patients are influenced by loading conditions, previous studies have shown conflicting results. The present study calculated LV elastance, which is a robust method to quantify LV function. We demonstrate that LV loading in MS patients is elevated but normalizes after valve repair and might be a result of reflex pathways. Additionally, we show that the LV in MS is less compliant than normal due to a combination of right ventricular loading and the valvular disease itself. Immediately after valve dilatation the increase in blood inflow into the LV results in even greater LV stiffness. Our findings enrich our understanding of heart function in MS patients and provide a simple reproducible way of assessing LV performance in MS. ABSTRACT Left ventricular (LV) function in rheumatic mitral stenosis (MS) remains an issue of controversy, due to load dependency of previously employed assessment methods. We investigated LV performance in MS employing relatively load-independent indices robust to the altered loading state. We studied 106 subjects (32 ± 8 years, 72% female) with severe MS (0.8 ± 0.2 cm(2) ) and 40 age-matched controls. MS subjects underwent simultaneous bi-ventricular catheterization and transthoracic echocardiography (TTE) before and immediately after percutaneous transvenous mitral commisurotomy (PTMC). Sphygmomanometric brachial artery pressures and TTE recordings were simultaneously acquired in controls. Single-beat LV elastance (Ees ) was employed for LV contractility measurements. Effective arterial elastance (Ea ) and LV diastolic stiffness were measured. MS patients demonstrated significantly elevated afterload (Ea : 3.0 ± 1.3 vs. 1.5 ± 0.3 mmHg ml(-1) ; P

The parameterized diastolic filling (PDF) method can be used to study the mechanics of early diastolic left ventricular (LV) filling. However, there are no publications describing the reference ranges of the PDF parameters. This study retrospectively recruited patients with normal results on rest and stress echocardiography and no diabetes or hypertension (n=138, 45% female). DICOM images of the resting E-wave from transmitral pulsed wave Doppler flow velocities were analyzed using freely available software. Viscoelastic energy loss (c) and stiffness (k) were higher in males compared to females (p≤0.001 for both). There were no correlations between any of the PDF parameters and age (p>0.05 for all). In males, stiffness was correlated with systolic blood pressure (r=0.24, p=0.04), and load and filling energy were correlated with diastolic blood pressure (r=-0.27, p=0.02, and r=-0.29, p=0.01, respectively). Sex-specific normal 95% reference limits for PDF analysis of early LV filling are presented for clinical use.

The use of consumer-grade wearables for purposes beyond fitness tracking has not been comprehensively explored. We generated and analyzed multidimensional data from 233 normal volunteers, integrating wearable data, lifestyle questionnaires, cardiac imaging, sphingolipid profiling, and multiple clinical-grade cardiovascular and metabolic disease markers. We show that subjects can be stratified into distinct clusters based on daily activity patterns and that these clusters are marked by distinct demographic and behavioral patterns. While resting heart rates (RHRs) performed better than step counts in being associated with cardiovascular and metabolic disease markers, step counts identified relationships between physical activity and cardiac remodeling, suggesting that wearable data may play a role in reducing overdiagnosis of cardiac hypertrophy or dilatation in active individuals. Wearable-derived activity levels can be used to identify known and novel activity-modulated sphingolipids that are in turn associated with insulin sensitivity. Our findings demonstrate the potential for wearables in biomedical research and personalized health.

ObjectivesWe aimed to analyse outcomes of ticagrelor and clopidogrel stratified by estimated glomerular filtration rate (eGFR) in a large unselected cohort of patients with acute myocardial infarction (MI).MethodsWe used follow-up data in MI survivors discharged on ticagrelor or clopidogrel enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry. The association between ticagrelor versus clopidogrel and the primary composite outcome of death, MI or stroke and the secondary outcome rehospitalisation with bleeding diagnosis at 1 year, was studied using adjusted Cox proportional hazards models, stratifying after eGFR levels.ResultsIn total, 45 206 patients with MI discharged on clopidogrel (n=33 472) or ticagrelor (n=11 734) were included. The unadjusted 1-year event rate for the composite endpoint of death, MI or stroke was 7.0%, 18.0% and 48.0% for ticagrelor treatment and 11.0%, 33.0% and 64.0% for clopidogrel treatment in patients with eGFR>60 (n=33 668), eGFR30–60 (n=9803) and eGFR (n=1735), respectively. After adjustment, ticagrelor as compared with clopidogrel was associated with a lower 1-year risk of the composite outcome (eGFR>60: HR 0.87, 95% CI 0.76 to 99, eGFR30–60: 0.82 (0.70 to 0.97), eGFR: 0.95 (0.69 to 1.29), P for interaction=0.55) and a higher risk of bleeding (eGFR>60: HR 1.10, 95% CI 0.90 to 1.35, eGFR30–60: 1.13 (0.84 to 1.51), eGFR: 1.79 (1.00 to 3.21), P for interaction=0.30) across the eGFR strata.ConclusionsTreatment with ticagrelor as compared with clopidogrel in patients with MI was associated with lower risk for the composite of death, MI or stroke and a higher bleeding risk across all strata of eGFR. Of caution, bleeding events were more abundant in patients with eGFR.

Background The combination of deformation analysis with conventional wall motion scoring (WMS) has been shown to increase the diagnostic sensitivity of dobutamine stress echocardiography (DSE). The feasibility and diagnostic power of WMS is largely improved by contrast agents; however, they are not used in combination with deformation analysis, as contrast agents are generally considered to render strain measurement unfeasible. Aims To assess the feasibility of tissue velocity (TVI)- and 2D speckle tracking (ST)-based strain analysis during contrast-enhanced DSE; and to show whether there is an incremental value in combining deformation analysis with contrast-enhanced WMS. Methods DS echocardiograms containing native, tissue Doppler, and contrast-enhanced loops of 60 patients were analysed retrospectively. The feasibility of WMS, TVI-, and ST-strain measurement was determined in 40 patients according to pre-defined criteria. The diagnostic ability of a combined protocol integrating data from contrast-WMS and TVI-strain measurement was then compared with contrast-WMS alone in all 60 patients, using coronary angiograms as a gold standard. Results Both TVI- and ST-based strain analysis were feasible during contrast-DSE (feasibility at peak stress: 87 and 75%). At the patient level, the diagnostic accuracy of the combined method did not prove superior to contrast-WMS (82 vs. 78%); a trend towards improved sensitivity and specificity for detecting coronary artery disease in the right coronary artery circulation (sensitivity: 85 vs. 77%, P = NS; specificity: 96 vs. 94%) was, however, observed. Conclusion Both TVI- and ST-based myocardial deformation analysis are feasible during contrast-enhanced DSE, however, our results fail to demonstrate a clear diagnostic benefit of additional strain analysis over expert WMS alone.

AB Purpose: The objective of this study is to investigate the time course of autonomic tone changes after a first-time endurance running race participation and associations with postexertional high-sensitivity troponin (hsTnT) levels in middle-aged males. Methods: Male (n = 42) first-time long-distance running race (Lidingoloppet 30 km) participants >=45 yr (50.5 +/- 5) were examined. HR and HR variability (HRV) in the time domain (SDANN) was measured continuously from 2 d before to 4 d after the race using a wireless cardiovascular monitor that also recorded arrhythmia episodes. In addition, subjects were assessed pre- and postrace by medical history and physical examination, 12-lead ECG, blood tests including hsTnT, and echocardiography. Results: Compared with corresponding prerace values, nighttime (2:00-4:00 a.m.) HR was significantly elevated (63.6 +/- 9.4 vs 53.9 +/- 8.3 bpm, P < 0.001) on the first night postrace, whereas HRV remained reduced for a median of 64 h (interquartile range, 51-102 h). A prolonged HR recovery period (r = 0.48, P = 0.005) and a larger reduction in postrace HRV (r = -0.49, P = 0.003) correlated with higher postrace hsTnT levels. The association between reduced HRV and higher hsTnT remained significant after multivariate analysis ([beta] = -0.48, P = 0.01). No sustained ventricular arrhythmias were recorded, but atrial fibrillation occurred in two subjects. Conclusion: Endurance running race participation caused a prolonged alteration of autonomic tone. More marked and prolonged changes were associated with higher levels of hsTnT, suggesting that the magnitude of troponin increase after strenuous exercise may reflect the magnitude of exercise-induced cardiovascular stress.

OBJECTIVE Although enhanced external counterpulsation (EECP) provides symptom reduction in many patients with severe angina pectoris, one-quarter of patients fail to respond. Earlier reports have not clearly established whether and how EECP responders may be identified pre-hoc. We hypothesized that clinical and biochemical data may be used to predict EECP response. METHODS We explored a database of n=53 patients who had undergone clinically indicated EECP during 35 1-h sessions in our unit (65±7 years; 49 male), and sought to clarify which factors are predictive of response. Efficiency of counterpulsation was measured as the diastolic augmentation (DA) ratio, and was recorded both at beginning and end of the EECP treatment course. An increase in 6-min walk (6MW) distance of 5% was indicative of clinical response. RESULTS Response occurred in 28 patients (53%; nonresponse in n=25, 47%). Responders had shorter baseline 6MW distance (377±81 vs. 445±62 m; P

Exercise can lead to release of biomarkers such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), a poorly understood phenomenon proposed to especially occur with high-intensity exercise in less trained subjects. We hypothesised that haemodynamic perturbations during exercise are larger in athletes with cTnT release, and studied athletes with detectable cTnT levels after an endurance event (HIGH; n = 16; 46 ± 9 years) against matched controls whose levels were undetectable (LOW; n = 11; 44 ± 7 years). Echocardiography was performed at rest and at peak supine bicycle exercise stress. Left ventricular (LV) end-systolic elastance (E (LV) a load-independent measure of LV contractility), effective arterial elastance (E (A) a lumped index of arterial load) and end-systolic meridional wall stress were calculated from cardiac dimensions and brachial blood pressure. Efficiency of cardiac work was judged from the ventriculo-arterial coupling ratio (E (A)/E (LV): optimal range 0.5-1.0). While subgroups had similar values at rest, we found ventriculo-arterial mismatch during exercise in HIGH subjects [0.47 (0.39-0.58) vs. LOW: 0.73 (0.62-0.83); p 0.01] due to unopposed increase in E (LV) (p 0.05). In LOW subjects, a greater increase occurred in E (A) during exercise (+81 ± 67 % vs. HIGH: +39 ± 32 %; p = 0.02) which contributed to a maintained coupling ratio. Subjects with higher baseline NT-proBNP had greater systolic wall stress during exercise (R (2) = 0.39; p 0.01) despite no correlation at rest (p = ns). In conclusion, athletes with exercise-induced biomarker release exhibit ventriculo-arterial mismatch during exercise, suggesting non-optimal cardiac work may contribute to this phenomenon.

Elderly female hypertensives with arterial stiffening constitute a majority of patients with heart failure with preserved ejection fraction (HFpEF), a condition characterized by inability to increase cardiac stroke volume (SV) with physical exercise. As SV is determined by the interaction between the left ventricle (LV) and its load, we wished to study the role of arterial hemodynamics for exertional SV reserve in patients at high risk of HFpEF. Twenty-one elderly (67 ± 9 yr) female hypertensive patients were studied at rest and during supine bicycle stress using echocardiography including pulsed-wave Doppler to record flow in the LV outflow tract and arterial tonometry for central arterial pressure waveforms. Arterial compliance was estimated based on an exponential relationship between pressure and volume. The ratio of aortic pressure-to-flow in early systole was used to derive characteristic impedance, which was subsequently subtracted from total resistance (mean arterial pressure/cardiac output) to yield systemic vascular resistance (SVR). It was found that patients with depressed SV reserve ( NoRes; reserve

Prolonged exercise has been shown to lead to elevated levels of cardiac troponin and altered cardiac function on echocardiography. It is not known if cardiac synchrony is altered by prolonged exercise. The aims of this study were to assess changes in intra-left ventricular mechanical synchrony and circulating levels of cardiac troponin following prolonged exercise and to evaluate the importance of prior exposure to endurance racing.Forty-three male participants in a 30-km cross-country race (20 new participants at this event [median, 3 previous endurance races] age matched against 23 repeat participants [median, 31 previous endurance events]) were assessed prospectively 1 to 2 days before and 24 hours after the race using troponin T and Doppler tissue imaging analyzing the standard deviation of time to peak myocardial systolic velocity (T(s)-SD) in a six-basal, six-midventricular segment model measuring myocardial synchrony. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene was also analyzed, as I allele carriers reportedly have superior endurance performance, while the D allele predisposes to renin-angiotensin system-induced cardiac remodeling.Prerace troponin T was undetectable in all runners, and postrace levels were higher in new runners (median, 0.03 microg/L; interquartile range [IQR], 0.01-0.04 microg/L) than in repeat runners (median, 0.01 microg/L; IQR, 0.01-0.02 microg/L) (P = .03). Although new and repeat runners had similar T(s)-SD at baseline (32 msec [IQR, 22-43 msec] vs 34 msec [IQR, 29-45 msec], P = .13), dyssynchrony increased only in new runners (40 msec [IQR, 31-47 msec], P.001; in repeat runners, median, 38 msec [IQR, 29-43 msec], P = .30; median relative difference, +13% vs +5%, P = .02). ACE genotype distribution was similar in both groups. Multivariate analysis showed that (1) a lack of prior endurance exposure; (2) more copies of the ACE D allele; and (3) lower peak systolic velocity were independent predictors of postrace dyssynchrony (P.05 for all).Prolonged exertion increased ventricular mechanical dyssynchrony in new endurance participants and in ACE D allele carriers. The long-term impact of such changes warrants future study.

Although chest pain is one of the leading presenting complaints in the Emergency Department (ED), only 12-15% account for Acute Coronary Syndrome (ACS). Hence early triage and exclusion of ACS is crucial to improve ED throughput and workflow. We aim to determine and compare the accuracy of the

Cardiac biomarkers play an important role in the diagnosis of cardiovascular disease. Elevated levels can be seen in the context of strenuous exercise. We studied this phenomenon in senior endurance runners. We included 185 participants (61.1 +/- 5 years; 29% women) at a 30-km cross-country race who were self-reportedly in excellent health. Before and after the race, the creatinine, N-terminal pro-brain natriuretic peptide (NT-proBNP), and troponin T were analyzed, and participation in the number of previous races and the race duration were recorded. NT-proBNP increased from 53 ng/L (interquartile range 31 to 89) to 121 ng/L (interquartile range 79 to 184) and troponin T from undetectable to 0.01 microg/L (interquartile range 0.01 to 0.04). The independent predictors of a large NT-proBNP increase were (1) greater levels present at baseline, (2) a greater increase in creatinine (both p0.001), (3) older age (p = 0.01), and (4) a longer race duration (p0.05). Troponin T elevation was independently predicted by (1) older age (p = 0.01), (2) a greater increase in creatinine, and (3) participation in fewer previous races (both p0.05). Of the 15 runners with an elevated (194 ng/L) baseline NT-proBNP level (8.1% of 185), 4 were found to have serious cardiovascular disease (2.2% of whole sample). Of these 4 patients, 1 died from sudden cardiac death within months after the race. In conclusion, biomarker elevation occurs commonly in senior runners. A high baseline NT-proBNP is predictive of a large release during exercise, suggesting that the factors that control the at rest levels also determine its release with exertion. Troponin T elevation was seen in less-experienced participants. A small group of very ill runners were identified by NT-proBNP analysis.

Prolonged exercise can induce cardiac fatigue, which is characterized by biomarker release and impaired myocardial function. The impact on ventricular electrophysiology is largely unknown.The objective of this study was to examine changes in ventricular repolarization after a 30-km cross-country race in runners agedor=55 years.Fifteen healthy participants (62 +/- 5 years) were assessed using biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], troponin T [TnT]), tissue Doppler echocardiography, and vectorcardiography at baseline, within 1 hour postrace and on days 1 and 6 postrace.During the race, NT-proBNP increased from 42 ng/L (interquartile range 25-117) to 187 ng/L (113-464), and TnT increased from undetectable levels to 0.03 microg/L (0.015-0.05). Global strain (19.1% +/- 2.2%) decreased on day 1 (17.2% +/- 1.8%) and day 6 (17.9% +/- 1.5%; P.01). QT(c) increased from 431 +/- 15 ms prerace to 445 +/- 22 ms postrace and 445 +/- 15 ms on day 1 (P.05), mainly because of an increased T(peak-end) interval (prerace 108 +/- 13 ms, postrace 127 +/- 43 ms, day 1 127 +/- 43 ms; P.05). Postrace, T(area) (baseline 75 +/- 26 microVs) peaked on day 1 (105 +/- 42 microVs) and remained high on day 6 (89 +/- 37 microVs; P.05). Runners with higher baseline NT-proBNP developed greater impairment of myocardial velocities (rho = -0.68 to -0.54; P.05) and a larger increase in T(area) (rho = 0.73; P.01).Cardiac fatigue induced by prolonged exertion is associated with sustained abnormalities in ventricular repolarization. Runners with higher baseline NT-proBNP are especially liable to such alterations of cardiac function.

A hallmark of mitral stenosis (MS) is the markedly altered left ventricular (LV) loading. As most of the methods used to determine LV performance in MS patients are influenced by loading conditions, previous studies have shown conflicting results. The present study calculated LV elastance, which is a robust method to quantify LV function. We demonstrate that LV loading in MS patients is elevated but normalizes after valve repair and might be a result of reflex pathways. Additionally, we show that the LV in MS is less compliant than normal due to a combination of right ventricular loading and the valvular disease itself. Immediately after valve dilatation the increase in blood inflow into the LV results in even greater LV stiffness. Our findings enrich our understanding of heart function in MS patients and provide a simple reproducible way of assessing LV performance in MS.Left ventricular (LV) function in rheumatic mitral stenosis (MS) remains an issue of controversy, due to load dependency of previously employed assessment methods. We investigated LV performance in MS employing relatively load-independent indices robust to the altered loading state. We studied 106 subjects (32 ± 8 years, 72% female) with severe MS (0.8 ± 0.2 cm(2) ) and 40 age-matched controls. MS subjects underwent simultaneous bi-ventricular catheterization and transthoracic echocardiography (TTE) before and immediately after percutaneous transvenous mitral commisurotomy (PTMC). Sphygmomanometric brachial artery pressures and TTE recordings were simultaneously acquired in controls. Single-beat LV elastance (Ees ) was employed for LV contractility measurements. Effective arterial elastance (Ea ) and LV diastolic stiffness were measured. MS patients demonstrated significantly elevated afterload (Ea : 3.0 ± 1.3 vs. 1.5 ± 0.3 mmHg ml(-1) ; P 0.001) and LV contractility (Ees : 4.1 ± 1.6 vs. 2.4 ± 0.5 mmHg ml(-1) ; P 0.001) as compared to controls, with higher Ea in subjects with smaller mitral valve area (≤ 0.8 cm(2) ) and pronounced subvalvular fusion. Stroke volume (49 ± 16 to 57 ± 17 ml; P 0.001) and indexed LV end-diastolic volume (LVEDVindex : 57 ± 16 to 64 ± 16 ml m(-2) ; P 0.001) increased following PTMC while Ees and Ea returned to more normal levels. Elevated LV stiffness was demonstrated at baseline and increased further following PTMC. Our findings provide evidence of elevated LV contractility, increased arterial load and increased diastolic stiffness in severe MS. Following PTMC, both LV contractility and afterload tend to normalize.

AB Purpose: This study aimed to assess the prevalence and patterns of early repolarization (ER) in middle-age long-distance runners, its relation to cardiac structure and function, and its response to strenuous physical activity. Methods: Male first-time cross-country race participants >45 yr were assessed pre- and postrace by medical history and physical examination, 12-lead ECG, vectorcardiography, blood tests, and echocardiography. ER was defined either as ST elevation or J wave and categorized according to localization and morphology. Results: One hundred and fifty-one subjects (50 +/- 5 yr) were evaluated before the race, and 47 subjects were evaluated after the race. Altogether, 67 subjects (44%) had ER. Subjects with versus without ER had a lower resting HR (56 +/- 8 vs 69 +/- 9 bpm, P = 0.02), lower body mass index (24 +/- 2 vs 25 +/- 3 kg[middle dot]m-2, P < 0.001), higher training volume (3.0 +/- 2.6 vs 2.1 +/- 2.7 h[middle dot]wk-1, P = 0.03), and faster 30-km running times (194 +/- 28 vs 208 +/- 31 min, P = 0.01). Vectorcardiography parameters in subjects with ER showed more repolarization heterogeneity: vector gradient (QRS-Tarea) (120 +/- 25 vs 92 +/- 29 [mu]Vs, P < 0.001), Tarea (105 +/- 18 vs 73 +/- 23 [mu]Vs, P < 0.001), and Tamplitude (0.63 +/- 0.13 vs 0.53 +/- 0.16 mm, P < 0.001); these parameters were inversely related to HR (r = -0.37 to -0.48, P < 0.001). ER disappeared in 15 (75%) of 20 subjects after the race. Conclusions: ER is a common finding in middle-age male runners. This ECG pattern, regardless of morphology and localization, is associated with normal cardiac examinations including noninvasive electrophysiology, features of better physical conditioning, and disappears after strenuous exercise in most cases. These findings support that ER should be regarded as a common and training-related finding also in middle-age physically active men.

Severe Plasmodium falciparum malaria is characterized by excessive sequestration of infected and uninfected erythrocytes in the microvasculature of the affected organ. Rosetting, the adhesion of P. falciparum–infected erythrocytes to uninfected erythrocytes is a virulent parasite phenotype associated with the occurrence of severe malaria. Here we report on the identification by single-cell reverse transcriptase PCR and cDNA cloning of the adhesive ligand P. falciparum erythrocyte membrane protein 1 (PfEMP1). Rosetting PfEMP1 contains clusters of glycosaminoglycan-binding motifs. A recombinant fusion protein (Duffy binding-like 1–glutathione S transferase; Duffy binding-like-1–GST) was found to adhere directly to normal erythrocytes, disrupt naturally formed rosettes, block rosette reformation, and bind to a heparin-Sepharose matrix. The adhesive interactions could be inhibited with heparan sulfate or enzymes that remove heparan sulfate from the cell surface whereas other enzymes or similar glycosaminoglycans of a like negative charge did not affect the binding. PfEMP1 is suggested to be the rosetting ligand and heparan sulfate, or a heparan sulfate–like molecule, the receptor both for PfEMP1 binding and naturally formed erythrocyte rosettes.

Background Traditional echocardiographic methods like left ventricular ejection fraction(EF) and wall motion scoring (WMS) and new methods like speckle tracking (ST) based 2D strain carry important prognostic information in acute coronary syndrome (ACS) patients. Parameters from tissue Doppler imaging (TDI), with its high time resolution, may further increase the prognostic value. Peak systolic velocity (PSV) of the basal segments of the left ventricle from TDI is a robust and user independent parameter. The aim was to investigate the prognostic value of PSV compared to EF, WMS, 2D strain and E/e'. Methods Echocardiographic images were collected and post processed in 227 ACS patients. Additional clinical data was prospectively gathered and patients were followed for 3-5 years regarding the combined endpoint of death or re-admission due to ACS or heart failure. Results The combined endpoint occurred in 85 (37%) patients. Those with an event had lower median PSV than those without (4,4 cm/s) vs. (5,3 cm/s), (p

Abnormal vascular-ventricular coupling has been suggested to contribute to heart failure with preserved ejection fraction in elderly females. Failure to increase stroke volume (SV) during exercise occurs in parallel with dynamic changes in arterial physiology leading to increased afterload. Such adverse vascular reactivity during stress may reflect either sympathoexcitation or be due to tachycardia. We hypothesized that afterload elevation induces SV failure by transiently attenuating left ventricular relaxation, a phenomenon described in animal research. The respective roles of tachycardia and sympathoexcitation were investigated in n = 28 elderly females (70 ± 4 yr) carrying permanent pacemakers. At rest, during atrial tachycardia pacing (ATP; 100 min−1) and during cold pressor test (hand immersed in ice water), we performed Doppler echocardiography (maximal untwist rate analyzed by speckle tracking imaging of rotational mechanics) and arterial tonometry (arterial stiffness estimated as augmentation index). Estimation of arterial compliance was based on an exponential relationship between arterial pressure and volume. We found that ATP produced central hypovolemia and a reduction in SV which was larger in patients with stiffer arteries (higher augmentation index). There was an associated adverse response of arterial compliance and vascular resistance during ATP and cold pressor test, causing an overall increase in afterload, but nonetheless enhanced maximal rate of untwist and no evidence of afterload-dependent failure of relaxation. In conclusion, tachycardia and cold provocation in elderly females produces greater vascular reactivity and SV failure in the presence of arterial stiffening, but SV failure does not arise secondary to afterload-dependent attenuation of relaxation.

Background Aortic stenosis (AS) is a relevant common valve disorder. Severe AS and symptoms and/or left ventricular dysfunction (EF Aim of the study is to assess the aortic annulus diameter in patients undergoing TAVI by biplane (BP) mode using transesophageal echocardiography (TEE) and compare it to two-dimensional (2D) transthoracic echocardiography (TTE) and 2DTEE using three-dimensional (3D) TEE as reference method. Methods The study population consisted of 50 patients retrospectively (24 men and 26 women, mean age 85±8 years of age) who all had undergone echocardiography examination prior to TAVI. Results The mean aortic annulus diameter was 20.4±2.2 mm with TTE, 22.3±2.5 mm with 2DTEE, 22.9±1.9 mm with BP-mode and 23.1±1.9 mm with 3DTEE. TTE underestimated the mean aortic annulus diameter in comparison to transesophageal imaging modalities (p Conclusion A multi-dimensional method is preferred to assess aortic annulus diameter in TAVI patients since there is risk of underestimation using single plane. Biplane mode is the method of choice in view of speedy post-processing with no need for expensive dedicated software. Lastly, single plane methods lead to misclassification of patients as unsuitable for TAVI. This may be of major clinical importance.

Ticagrelor led to greater reduction in ischemic events than clopidogrel in patients with acute coronary syndrome (ACS) in the PLATO trial. We evaluated outcomes with ticagrelor vs. clopidogrel post-ACS in a real-world setting. We studied a total of 45,073 consecutive ACS patients prospectively

Whether measurement of left ventricular outflow tract diameter (LVOTd) using color Doppler (CD) in order to more accurately define LVOTd is more accurate for determination of stroke volume (SV) than gray scale and compare it with direct measurement of LVOT area (a) using three-dimensional echocardiography (3DE) for SV determination.Twenty-one volunteers were examined. LVOTa was calculated by two-dimensional echocardiography (2DE) using the following formula: π× (d/2)(2) , d = LVOT diameter by gray scale and CD, respectively. Planimetry of LVOTa was performed in parasternal long axis using 3DE. Eccentricity Index was calculated using the lateral and anterior-posterior LVOTd. SV was obtained by four different methods: (1) 2D gray scale, (2) 2D color, (3) LVOTa × LVOT velocity time integral, and (4) SV by Simpson's biplane method. Gray scale LVOTd was significantly smaller compared to LVOTd obtained with CD (P0.05). Significant differences occurred between LVOTa gray scale and CD (3.29 ± 0.74 cm(2) vs 3.67 ± 0.70 cm(2) , P0.05) and between LVOTa calculated by gray scale in comparison to 3DE planimetry; (3.29 ± 0.74 cm(2) vs 3.61 ± 0.89 cm(2) , P = 0.011). Half of the subjects had at least 17% difference between the lateral and anterior-posterior LVOTd. There were significant differences between SV by 2D gray scale and 2D CD (82.8 ± 17.1 mL vs 92.4 ± 16.8 mL, P0.05) and between 2D gray scale and 3DE planimetry (82.8 ± 17.1 mL vs 90.7 ± 19.8 mL, P = 0.025).Our study demonstrates LVOT being frequently elliptical. SV and LVOTa were found to be similar when comparing 2DE CD and 3DE planimetry and showed higher values in comparison to 2DE gray scale, which suggests 2DE CD to be an alternative approach for SV assessment.

Purpose: Long-distance running events enjoy increasing popularity in all ages. Whereas the health benefits of regular moderate exercise are undisputed, the net health effects of single or repeated participation in endurance events of marathon type remain to be determined. We wanted to investigate performance trends over time and the relationship between race performance and cardiac biomarker levels among participants in a large annual 30-km cross-country race. Methods: We analyzed a database containing age, gender, run times, and previous race participation of 124,608 runners finishing the Lidingoloppet (30 km) between 1993 and 2007. In 249 male runners age =45 yr, we also performed a thorough cardiovascular examination, including measuring the cardiac biomarkers N-terminal pro�brain natriuretic peptide (NT-proBNP) and troponin. Results: Total participation increased 56% with the largest gains in younger female and older male runners. Mean run times rose from 164 ± 27 min in 1993 to 184 ± 33 min in 2007 (P < 0.001) in men and from 179 ± 26 to 203 ± 32 in women (P < 0.001) after a strong linear relationship (men, r = 0.98; women, r = 0.93). Increased run times were seen in the mean, top, and bottom quartiles as well as in the top and bottom 5% of all age and gender groups. In the substudy among 249 older male runners, not only higher body mass index, older age, and fewer previous race participations but also higher baseline NT-proBNP was independently associated with increased run time. Conclusions: Whereas participation in the Lidingoloppet increased, fitness deteriorated over time in both genders and in all ages. In a subset of older male athletes, longer run times were associated with higher levels of NT-proBNP. The present findings may support the usefulness of preparticipation evaluation to ensure appropriate fitness and cardiovascular health in long-distance race participants

The ratio of the early transmitral flow velocity to the early diastolic tissue velocity (E/Em) has been suggested as a reliable estimate of left ventricular diastolic pressures (LVDP). However, the evidence regarding the ability of E/Em to detect LVDP changes is relatively equivocal. Our aim was to evaluate the validity of the ratio following acute load reduction.68 consecutive patients referred for coronary angiography underwent LV catheterization and echocardiography simultaneously. Doppler signals of transmitral flow and spectral TD signals at the level of the mitral annulus were obtained before and directly after intravenous administration of nitroglycerin (NTG). The predictive ability of E/Em to identify elevated LVDP was modest (area under curve=0.71 ± 0.08, p0.01). The index was more strongly associated with LVDP in patients with reduced ejection fraction (EF)55% (r=0.68; p0.01) than in patients with normal EF. Following NTG, E/Em lacked any predictive potential for elevated LVDP whereas changes LVDP could not be reliably tracked using E/Em.The predictive capacity of E/Em for elevated LVDP was weak and declined significantly following acute reduction in LV load. Changes in LVDP were not reliably predicted by E/Em. The current findings derived from a real-world patient population with relatively high filling pressures indicate that E/Em may not be sufficiently robust to be employed as a single non-invasive estimate of LVDP nor for monitoring load reducing medical therapy.

The assessment of left ventricular (LV) systolic function is frequently the most important task during the echocardiography examination. LV ejection fraction (EF) is the most commonly used measure to assess LV systolic function. EF is well established, with strong prognostic and therapeutic implications, but, nevertheless, it may not always be satisfactory in all patients. Other measures of myocardial contractility can provide valuable additive information in some patients. This is particularly true in patients with suspected heart failure but normal EF. The measurement of longitudinal function using M-mode and/or deformation analysis from tissue Doppler data or speckle tracking algorithms can be useful in this respect. Regional LV dysfunction can be difficult to detect using visual semi-quantitative assessment of regional wall motion. Contrast echocardiography can be most helpful in delineating the LV endocardial border and, thus, increasing sensitivity for detecting wall motion abnormalities. Deformation analysis can also be helpful for detecting subtle wall motion abnormalities, but these methods should be used with caution due to measurement variability and image quality dependence.

Aims The aim of this study was to study the haemodynamic effect of atrioventricular delay (AVD) modifications within a narrow range in different body positions and during exercise in patients receiving cardiac resynchronization therapy (CRT). Methods The previously optimized AVD was shortened and prolonged by 40 ms in 27 CRT patients and 9 controls without heart failure. Cardiac output (CO) was measured by inert gas rebreathing (Innocor) as the average over different body positions (left-lateral, supine, sitting, standing, and exercise). In eight CRT patients with an implantable haemodynamic monitor, the estimated pulmonary artery diastolic pressure (ePAD) was analysed. Results The magnitude of CO response to AVD changes was greater in CRT patients than in controls (0.25 vs. 0.20 L/min, P < 0.05), varied substantially between individuals (range: 0.12–0.56 L/min), and correlated with left atrial size ( r = 0.61, P < 0.001). On average, AVD shortening decreased CO slightly (0.07 ± 0.17 L/min) and increased ePAD (1.1 ± 0.8 mmHg, both P < 0.05), whereas prolongation had no significant effect. Conclusion The haemodynamic response to AVD modifications within a narrow range is larger in CRT patients than in normal controls and varies substantially between individuals. These findings suggest that optimal AVD tuning is clinically important in selected patients.

Cardiac biomarker release after endurance exercise has been described in young athletes. Although older athletes are increasingly active in such sports, they have not previously been studied. Therefore, the aim of this study was to assess the magnitude and reproducibility of biomarker release in athletes agedor =55 years. Forty-three healthy athletes (mean age 61 +/- 3.6 years) were assessed before and immediately after a 30-km cross-country race and studied with echocardiography at rest. The median N-terminal pro-brain natriuretic peptide (NT-proBNP; normal194 ng/L) level was 42 ng/L (interquartile range 30 to 95) at baseline and 191 ng/L (interquartile range 114 to 308) after the race. Troponin T (normal0.03 microg/L) was elevated in 19 subjects (44%) after the race. Twenty-two subjects had also been studied 3 years before at the same race, using an identical test protocol. Between the 2 races, strong correlations were seen for individual runners' postrace biomarker levels (NT-proBNP: r = 0.82, log transformed data; troponin T: Spearman's rho = 0.84; p0.001 for both). The coefficient of variation for NT-proBNP release was 8.1%. Levels of NT-proBNP after the race were correlated with levels at baseline (r = 0.93, p0.001) and with left ventricular mass index (r = 0.32, p = 0.03). Moreover, participants with elevated postrace NT-proBNP were significantly older (62.0 vs 59.8 years, p = 0.04). In conclusion, long-distance runners agedor =55 years released NT-proBNP and troponin T in a reproducible fashion. The magnitude of NT-proBNP release during the race was correlated strongly with NT-proBNP baseline levels and was associated with left ventricular mass and age. These findings may suggest a potential adverse effect of long-distance running on cardiac function in certain participants in this age group.