Recently, myocardial work analysis as an echocardiographic tool to non-invasively determine LV work has been introduced and validated against invasive measurements. Based on systolic blood pressure ...and speckle-tracking derived longitudinal strain (GLS) during systole and isovolumic relaxation, it is considered less load-dependent than LV ejection fraction (LVEF) or GLS and to integrate information on LV active systolic and diastolic work. We aimed to establish reference values for global constructive (GCW) and global wasted work (GWW) as well as of global work index (GWI) and global work efficiency (GWE) across a wide age range and to assess the association with standard echocardiography parameters to estimate the potential additional information provided by myocardial work (MyW). The Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study carefully characterized a representative sample of the population of the City of Würzburg, Germany, aged 30-79 years. We performed myocardial work analysis using the standardized, quality-controlled transthoracic echocardiograms of all individuals lacking any cardiovascular risk factor. Out of 4965 participants, 779 (49±10 years, 59% women) were eligible for the present analysis. Levels of GCW, GWW, and GWE were independent of sex and body mass index, and were stable until the age of 45 years. Thereafter, we observed an upward shift to further stable values of GCW and a linear increase of GWW with advancing age, resulting in lower GWE. Age-adjusted percentiles for GCW, GWW, GWI, and GWE were derived. Higher levels of blood pressure or LV mass were associated with higher GCW, GWI, and GWW, resulting in lower GWE; higher LVEF correlated with higher GCW and GWI, but lower GWW. Higher E/e' correlated with higher GWW, higher e' with lower GWW. Derived from a large sample of apparently healthy individuals from a population based-cohort, we provide age-adjusted reference values for myocardial work indices, applicable for either sex. Weak correlations with common echocardiographic parameters suggest MyW indices to potentially provide additional information, which has to be evaluated in diseased patient cohorts.
Although stroke is acknowledged as a long-term condition, population estimates of outcomes longer term are lacking. Such estimates would be useful for planning health services and developing research ...that might ultimately improve outcomes. This burden of disease study provides population-based estimates of outcomes with a focus on disability, cognition, and psychological outcomes up to 10 y after initial stroke event in a multi-ethnic European population.
Data were collected from the population-based South London Stroke Register, a prospective population-based register documenting all first in a lifetime strokes since 1 January 1995 in a multi-ethnic inner city population. The outcomes assessed are reported as estimates of need and included disability (Barthel Index <15), inactivity (Frenchay Activities Index <15), cognitive impairment (Abbreviated Mental Test < 8 or Mini-Mental State Exam <24), anxiety and depression (Hospital Anxiety and Depression Scale >10), and mental and physical domain scores of the Medical Outcomes Study 12-item short form (SF-12) health survey. Estimates were stratified by age, gender, and ethnicity, and age-adjusted using the standard European population. Plots of outcome estimates over time were constructed to examine temporal trends and sociodemographic differences. Between 1995 and 2006, 3,373 first-ever strokes were registered: 20%-30% of survivors had a poor outcome over 10 y of follow-up. The highest rate of disability was observed 7 d after stroke and remained at around 110 per 1,000 stroke survivors from 3 mo to 10 y. Rates of inactivity and cognitive impairment both declined up to 1 y (280/1,000 and 180/1,000 survivors, respectively); thereafter rates of inactivity remained stable till year eight, then increased, whereas rates of cognitive impairment fluctuated till year eight, then increased. Anxiety and depression showed some fluctuation over time, with a rate of 350 and 310 per 1,000 stroke survivors, respectively. SF-12 scores showed little variation from 3 mo to 10 y after stroke. Inactivity was higher in males at all time points, and in white compared to black stroke survivors, although black survivors reported better outcomes in the SF-12 physical domain. No other major differences were observed by gender or ethnicity. Increased age was associated with higher rates of disability, inactivity, and cognitive impairment.
Between 20% and 30% of stroke survivors have a poor range of outcomes up to 10 y after stroke. Such epidemiological data demonstrate the sociodemographic groups that are most affected longer term and should be used to develop longer term management strategies that reduce the significant poor outcomes of this group, for whom effective interventions are currently elusive. Please see later in the article for the Editors' Summary.
Intracerebral hemorrhage (ICH) is the most devastating adverse event in patients receiving oral anticoagulation. There is only sparse evidence regarding ICH related to the use of non-vitamin K ...antagonist oral anticoagulant (NOAC) agents.
To evaluate the early clinical and radiological course, acute management, and outcome of ICH related to NOAC use.
Prospective investigator-initiated, multicenter observational study. All diagnostic and treatment decisions, including administration of hemostatic factors (eg, prothrombin complex concentrate), were left to the discretion of the treating physicians. The setting was 38 stroke units across Germany (February 1, 2012, to December 31, 2014). The study included 61 consecutive patients with nontraumatic NOAC-associated ICH, of whom 45 (74%) qualified for the hematoma expansion analysis.
Hematoma expansion, intraventricular hemorrhage, and reversal of anticoagulation during the acute phase. Recorded were the 3-month functional outcome, factors associated with an unfavorable outcome (modified Rankin Scale score, 3-6), any new intraventricular extension or an increase in the modified Graeb score by at least 2 points, and the frequency of substantial hematoma expansion (defined as relative ≥ 33% or absolute ≥ 6-mL volume increase).
In total, 41% (25 of 61) of patients with NOAC-associated ICH were female, and the mean (SD) patient age was 76.1 (11.6) years. At admission, the median National Institutes of Health Stroke Scale score was 10 (interquartile range, 4-18). The mean (SD) baseline hematoma volume was 23.7 (31.3) mL. In patients with sequential imaging for the hematoma expansion analysis, substantial hematoma expansion occurred in 38% (17 of 45). New or increased intraventricular hemorrhage was observed in 18% (8 of 45). Overall mortality was 28% (17 of 60 follow-up data were missing in 1 patient) at 3 months, and 65% (28 of 43) of survivors had an unfavorable outcome (modified Rankin Scale score, 3-6). Overall, 57% (35 of 61) of the patients received prothrombin complex concentrate, with no statistically significant effect on the frequency of substantial hematoma expansion (43% 12 of 28 for prothrombin complex concentrate vs 29% 5 of 17 for no prothrombin complex concentrate, P = .53), or on the occurrence of an unfavorable outcome (modified Rankin Scale score, 3-6) (odds ratio, 1.20; 95% CI, 0.37-3.87; P = .76).
Non-vitamin K antagonist oral anticoagulant-associated ICH has a high mortality and an unfavorable outcome, and hematoma expansion is frequent. Larger-scale prospective studies are needed to determine whether the early administration of specific antidotes can improve the poor prognosis of NOAC-associated ICH.
Objective
Cardiac diseases are established risk factors for ischemic stroke incidence and severity. Conversely, there is increasing evidence that brain ischemia can cause cardiac dysfunction. The ...mechanisms underlying this neurogenic heart disease are incompletely understood. Although it is established that ischemic stroke is associated with cardiac arrhythmias, myocardial damage, elevated cardiac enzymes, and plasma catecholamines in the acute phase, nothing is known about the delayed consequences of ischemic stroke on cardiovascular function.
Methods
To determine the long‐term cardiac consequences of a focal cerebral ischemia, we subjected young and aged mice to a 30‐minute transient middle cerebral artery occlusion and analyzed cardiac function by serial transthoracic echocardiography and hemodynamic measurements up to week 8 after surgery. Finally, animals were treated with metoprolol to evaluate a pharmacologic treatment option to prevent the development of heart failure.
Results
Focal cerebral ischemia induced a long‐term cardiac dysfunction with a reduction in left ventricular ejection fraction and an increase in left ventricular volumes; this development was associated with higher peripheral sympathetic activity. Metoprolol treatment prevented the development of chronic cardiac dysfunction by decelerating extracellular cardiac remodeling and inhibiting sympathetic signaling relevant to chronic autonomic dysfunction.
Interpretation
Focal cerebral ischemia in mice leads to the development of chronic systolic dysfunction driven by increased sympathetic activity. If these results can be confirmed in a clinical setting, treating physicians should be attentive to clinical signs of heart failure in every patient after ischemic stroke. Therapeutically, the successful β‐blockade with metoprolol in mice could also have future clinical implications. Ann Neurol 2017;82:729–743
Summary Background Atrial fibrillation is a major risk factor for recurrent ischaemic stroke, but often remains undiagnosed in patients who have had an acute ischaemic stroke. Enhanced and prolonged ...Holter-electrocardiogram-monitoring might increase detection of atrial fibrillation. We therefore investigated whether enhanced and prolonged rhythm monitoring was better for detection of atrial fibrillation than standard care procedures in patients with acute ischaemic stroke. Methods Find-AFRANDOMISED is an open-label randomised study done at four centres in Germany. We recruited patients with acute ischaemic stroke (symptoms for 7 days or less) aged 60 years or older presenting with sinus rhythm and without history of atrial fibrillation. Patients were included irrespective of the suspected cause of stroke, unless they had a severe ipsilateral carotid or intracranial artery stenosis, which were the exclusion criteria. We used a computer-generated allocation sequence to randomly assign patients in a 1:1 ratio with permuted block sizes of 2, 4, 6, and 8, stratified by centre, to enhanced and prolonged monitoring (ie, 10-day Holter-electrocardiogram ECG-monitoring at baseline, and at 3 months and 6 months of follow-up) or standard care procedures (ie, at least 24 h of rhythm monitoring). Participants and study physicians were not masked to group assignment, but the expert committees that adjudicated endpoints were. The primary endpoint was the occurrence of atrial fibrillation or atrial flutter (30 sec or longer) within 6 months after randomisation and before stroke recurrence. Because Holter ECG is a widely used procedure and not known to harm patients, we chose not to assess safety in detail. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT01855035. Findings Between May 8, 2013, and Aug 31, 2014, we recruited 398 patients. 200 patients were randomly assigned to the enhanced and prolonged monitoring group and 198 to the standard care group. After 6 months, we detected atrial fibrillation in 14% of 200 patients in the enhanced and prolonged monitoring group (27 patients) versus 5% in the control group (nine of 198 patients, absolute difference 9·0%; 95% CI 3·4–14·5, p=0·002; number needed to screen 11). Interpretation Enhanced and prolonged monitoring initiated early in patients with acute ischaemic stroke aged 60 years or older was better than standard care for the detection of atrial fibrillation. These findings support the consideration of all patients aged 60 years or older with stroke for prolonged monitoring if the detection of atrial fibrillation would result in a change in medical management (eg, initiation of anticoagulation). Funding Boehringer Ingelheim.
The impact of risk factors on poor outcome after ischemic stroke is well known, but estimating the amount of poor outcome attributable to single factors is challenging in presence of multimorbidity. ...We aim to compare population attributable risk estimates obtained from different statistical approaches regarding their consistency. We use a real-life data set from the PROSCIS study to identify predictors for mortality and functional impairment one year after first-ever ischemic stroke and quantify their contribution to poor outcome using population attributable risks.
The PROSpective Cohort with Incident Stroke (PROSCIS) is a prospective observational hospital-based cohort study of patients after first-ever stroke conducted independently in Berlin (PROSCIS-B) and Munich (PROSCIS-M). The association of baseline factors with poor outcome one year after stroke in PROSCIS-B was analysed using multiple logistic regression analysis and population attributable risks were calculated, which were estimated using sequential population attributable risk based on a multiple generalized additive regression model, doubly robust estimation, as well as using average sequential population attributable risk. Findings were reproduced in an independent validation sample from PROSCIS-M.
Out of 507 patients with available outcome information after 12 months in PROSCIS-B, 20.5% suffered from poor outcome. Factors associated with poor outcome were age, pre-stroke physical disability, stroke severity (NIHSS), education, and diabetes mellitus. The order of risk factors ranked by magnitudes of population attributable risk was almost similar for all methods, but population attributable risk estimates varied markedly between the methods. In PROSCIS-M, incidence of poor outcome and distribution of baseline parameters were comparable. The multiple logistic regression model could be reproduced for all predictors, except pre-stroke physical disability. Similar to PROSCIS-B, the order of risk factors ranked by magnitudes of population attributable risk was almost similar for all methods, but magnitudes of population attributable risk differed markedly between the methods.
Ranking of risk factors by population impact is not affected by the different statistical approaches. Thus, for a rational decision on which risk factor to target in disease interventions, population attributable risk is a supportive tool. However, population attributable risk estimates are difficult to interpret and are not comparable when they origin from studies applying different methodology. The predictors for poor outcome identified in PROSCIS-B have a relevant impact on mortality and functional impairment one year after first-ever ischemic stroke.
Psychosocial factors affect mental health and health-related quality of life (HRQL) in a complex manner, yet gender differences in these interactions remain poorly understood. We investigated whether ...psychosocial factors such as social support and personal and work-related concerns impact mental health and HRQL differentially in women and men during the first year of the COVID-19 pandemic. Between June and October 2020, the first part of a COVID-19-specific program was conducted within the "Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB)" cohort study, a representative age- and gender-stratified sample of the general population of Würzburg, Germany. Using psychometric networks, we first established the complex relations between personal social support, personal and work-related concerns, and their interactions with anxiety, depression, and HRQL. Second, we tested for gender differences by comparing expected influence, edge weight differences, and stability of the networks. The network comparison revealed a significant difference in the overall network structure. The male (N = 1370) but not the female network (N = 1520) showed a positive link between work-related concern and anxiety. In both networks, anxiety was the most central variable. These findings provide further evidence that the complex interplay of psychosocial factors with mental health and HRQL decisively depends on gender. Our results are relevant for the development of gender-specific interventions to increase resilience in times of pandemic crisis.
We aimed to systematically identify and evaluate all studies of good quality that compared the occurrence of mental disorders in the self-employed versus employees. Adhering to the Cochrane ...guidelines, we conducted a systematic review and searched three major medical databases (MEDLINE, Web of Science, Embase), complemented by hand search. We included 26 (three longitudinal and 23 cross-sectional) population-based studies of good quality (using a validated quality assessment tool), with data from 3,128,877 participants in total. The longest of these studies, a Swedish national register evaluation with 25 years follow-up, showed a higher incidence of mental illness among the self-employed compared to white-collar workers, but a lower incidence compared to blue-collar workers. In the second longitudinal study from Sweden the self-employed had a lower incidence of mental illness compared to both blue- and white-collar workers over 15 years, whereas the third longitudinal study (South Korea) did not find a difference regarding the incidence of depressive symptoms over 6 years. Results from the cross-sectional studies showed associations between self-employment and poor general mental health and stress, but were inconsistent regarding other mental outcomes. Most studies from South Korea found a higher prevalence of mental disorders among the self-employed compared to employees, whereas the results of cross-sectional studies from outside Asia were less consistent. In conclusion, we found evidence from population-based studies for a link between self-employment and increased risk of mental illness. Further longitudinal studies are needed examining the potential risk for the development of mental disorders in specific subtypes of the self-employed.
Acute kidney injury (AKI) is a postoperative complication after cardiac surgery with a high impact on mortality and morbidity. Nephrocheck® TIMP-2*IGFBP7 determines markers of tubular stress, which ...occurs prior to tubular damage. It is unknown at which time-point TIMP-2*IGFBP7 measurement should be performed to ideally predict AKI. We investigated the association of TIMP-2*IGFBP7 at various time-points with the incidence of AKI in patients undergoing elective cardiac surgery including cardio-pulmonary bypass.
In a prospective cohort study, serial blood and urine samples were collected from 150 patients: pre-operative, at ICU-admission, 24h and 48h post-surgery. AKI was defined as Serum-Creatinine rise >0.3 mg/dl within 48hrs. Urinary TIMP-2*IGFBP7 was measured at pre-operative, ICU-admission and 24h post-surgery; medical staff was kept blinded to these results.
A total of 35 patients (23.5%) experienced AKI, with a higher incidence in those with high TIMP-2*IGFBP7 values at ICU admission (57.1% vs. 10.1%, p<0.001). In logistic regression TIMP-2*IGFBP7 at ICU admission was independently associated with the occurrence of AKI (Odds Ratio 11.83; p<0.001, C-statistic= 0.74) after adjustment for EuroSCORE II and CBP-time.
Early detection of elevated TIMP-2*IGFBP7 at ICU admission was strongly predictive for postoperative AKI and appeared to be more precise as compared to subsequent measurements.
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