Stroke; A Journal Of Cerebral Circulation[JOURNAL]
Sun
200 papers
Components and Trends in Door to Treatment Times for Endovascular Therapy in Get With The Guidelines-Stroke Hospitals.
Menon BK, Xu H, Cox M … +13 more , Saver JL, Goyal M, Peterson E, Xian Y, Matsuoka R, Jehan R, Yavagal D, Gupta R, Mehta B, Bhatt DL, Fonarow GC, Schwamm LH, Smith EE
Circulation · 2019 Jan · PMID 30586703 · Publisher ↗
BACKGROUND: Endovascular therapy (EVT) is standard of care in patients with acute disabling ischemic stroke attributable to large-vessel occlusion and is more effective when delivered quickly. It is currently unclear whe...
BACKGROUND: Endovascular therapy (EVT) is standard of care in patients with acute disabling ischemic stroke attributable to large-vessel occlusion and is more effective when delivered quickly. It is currently unclear whether time targets achieved in clinical trials can be achieved in clinical practice. We describe interval times from patient arrival in the emergency department (door) to first pass (treatment initiation) in patients receiving EVT within Get With The Guidelines-Stroke hospitals and analyze patient- and hospital-level variables associated with these times. METHODS: Data are from sites participating fully as Comprehensive Stroke Centers within Get With The Guidelines-Stroke hospitals from October 2014 to September 2016. Workflow times analyzed include door to imaging, imaging to arterial access, arterial access to first pass, and the composite door to first pass time. Data are described overall and by calendar-year quarters. Multivariable modeling was used to identify patient- and hospital-level variables associated with workflow times. RESULTS: Among 2929 patients with EVT from 195 hospitals (median age, 71 years [interquartile range {IQR}, 60-81]; 50.7% female; median baseline National Institute of Health Stroke Score, 17 [IQR, 12-22]; median annual EVT administration number, 16 [IQR, 10-27]), median door to first pass time was 130 minutes (IQR, 101-170 minutes), door to imaging time was 12 minutes (IQR, 7-20 minutes), imaging to arterial puncture time was 93 minutes (IQR, 68-126 minutes), and arterial puncture to first pass time was 18 minutes (IQR, 4-31 minutes). Overall, 3% patients achieved a door to first pass time ≤60 minutes. A statistically significant linear time trend was noted for door to first pass time (quarter 4 year 2014 median time, 134.5 minutes to quarter 3 year 2016 median time, 128 minutes, P=0.002). In multivariable analysis, older age, arrival during nonregular hours, and history of diabetes mellitus were associated with longer door to first pass time. Hospitals achieving shorter door to intravenous alteplase administration (door to needle) times were more likely to achieve faster door to first pass time ( P<0.001). Each 5 cases/y increase in EVT case volume was associated with a 3% shorter door to first pass time, up to a case volume of 40 per year ( P<0.001). CONCLUSIONS: Although EVT treatment times are modestly improving, additional efforts are needed to streamline workflow so that the true potential of this treatment is realized. These data may inform benchmark goals for EVT workflow times.
Comprehensive Analysis of Stroke in the Long-Term Cohort of the MOMENTUM 3 Study.
Colombo PC, Mehra MR, Goldstein DJ … +18 more , Estep JD, Salerno C, Jorde UP, Cowger JA, Cleveland JC, Uriel N, Sayer G, Skipper ER, Downey FX, Ono M, Hooker R, Anyanwu AC, Givertz MM, Mahr C, Topuria I, Somo SI, Crandall DL, Horstmanshof DA
Circulation · 2019 Jan · PMID 30586698 · Publisher ↗
BACKGROUND: The MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) has demonstrated that the HeartMate 3 (HM3) pump is associated with...
BACKGROUND: The MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) has demonstrated that the HeartMate 3 (HM3) pump is associated with reduced strokes compared with the HeartMate II (HMII) device. We now perform a comprehensive analysis of stroke events to evaluate their longitudinal occurrence, clinical correlates, patterns, and impact on outcome across the 2-year duration of support. METHODS: MOMENTUM 3 is a randomized controlled trial of the HM3 centrifugal-flow pump versus the HMII axial-flow pump in patients with advanced heart failure, regardless of the intended goal of support (bridge to transplantation or destination therapy). Baseline and postimplantation clinical correlates of stroke events were assessed with multivariable analyses. Longitudinal patterns, including device association, type of stroke (hemorrhagic versus ischemic), changing severity of impairment assessed with the modified Rankin Scale (disabling [modified Rankin Scale score >3] versus nondisabling [modified Rankin Scale score ≤3]) over time, and association with outcome, were determined. RESULTS: In 361 patients with the intended implant (189 HM3 and 172 HMII), 65 strokes (40 ischemic strokes and 25 hemorrhagic strokes) occurred in 52 patients at a median of 131 (range, 1-733) days. No difference in stroke rate was noted between 0 and 180 days of follow-up between devices. However, stroke incidence in the long-term period (181-730 days after left ventricular assist device) was 3.3 times lower for the HM3 group (HM3: 0.04 versus HMII: 0.13 events per patient-year; odds ratio, 0.23; 95% CI, 0.08-0.63; P=0.01). Treatment with the HM3 pump was the only independent predictor of lower stroke events. We found no direct association of blood pressure or antithrombotic regimens with observed stroke rates. A stroke event significantly lowered 2-year postimplantation survival regardless of subtype or initial severity of neurological impairment compared with patients without a stroke (43±12% for hemorrhagic stroke, 57±9% for ischemic stroke, 51±11% for disabling, and 51±11% for nondisabling compared with 85±2% 2-year survival for patients without stroke). CONCLUSIONS: The HM3 pump is associated with a marked reduction in stroke rates compared with the HMII device, with benefits observed in the long-term period (>6 months). The occurrence of stroke of any type (hemorrhagic and ischemic) or of any functional severity (disabling and nondisabling) is predictive of a poor 2-year clinical outcome. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02224755.
Heart Failure With Preserved Ejection Fraction in the Young.
Tromp J, MacDonald MR, Tay WT … +12 more , Teng TK, Hung CL, Narasimhan C, Shimizu W, Ling LH, Ng TP, Yap J, McMurray JJV, Zile MR, Richards AM, Anand IS, Lam CSP
Circulation · 2018 Dec · PMID 30565987 · Publisher ↗
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF), traditionally considered a disease of the elderly, may also affect younger patients. However, little is known about HFpEF in the young. METHODS: We pros...
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF), traditionally considered a disease of the elderly, may also affect younger patients. However, little is known about HFpEF in the young. METHODS: We prospectively enrolled 1203 patients with HFpEF (left ventricular ejection fraction ≥50%) from 11 Asian regions. We grouped HFpEF patients into very young (<55 years of age; n=157), young (55-64 years of age; n=284), older (65-74 years of age; n=355), and elderly (≥75 years of age; n=407) and compared clinical and echocardiographic characteristics, quality of life, and outcomes across age groups and between very young individuals with HFpEF and age- and sex-matched control subjects without heart failure. RESULTS: Thirty-seven percent of our HFpEF population was <65 years of age. Younger age was associated with male preponderance and a higher prevalence of obesity (body mass index ≥30 kg/m; 36% in very young HFpEF versus 16% in elderly) together with less renal impairment, atrial fibrillation, and hypertension (all P<0.001). Left ventricular filling pressures and prevalence of left ventricular hypertrophy were similar in very young and elderly HFpEF. Quality of life was better and death and heart failure hospitalization at 1 year occurred less frequently ( P<0.001) in the very young (7%) compared with elderly (21%) HFpEF. Compared with control subjects, very young HFpEF had a 3-fold higher death rate and twice the prevalence of hypertrophy. CONCLUSIONS: Young and very young patients with HFpEF display similar adverse cardiac remodeling compared with their older counterparts and very poor outcomes compared with control subjects without heart failure. Obesity may be a major driver of HFpEF in a high proportion of HFpEF in the young and very young.
Evidence-Based Performance Measures and Outcomes in Patients With Acute Ischemic Stroke.
Wang Y, Li Z, Zhao X … +12 more , Liu L, Wang C, Wang C, Peterson ED, Schwamm LH, Fonarow GC, Smith SC, Bettger J, Wang D, Li H, Xian Y, Wang Y
Circ Cardiovasc Qual Outcomes · 2018 Dec · PMID 30557048 · Publisher ↗
BACKGROUND: Stroke is the leading cause of death in China. Despite the wide dissemination of evidence-based guidelines, data about adherence to these in routine clinical practice are scarce. We conducted a study using a...
BACKGROUND: Stroke is the leading cause of death in China. Despite the wide dissemination of evidence-based guidelines, data about adherence to these in routine clinical practice are scarce. We conducted a study using a nationwide registry to evaluate the implementation of evidence-based stroke performance indicators and associated guidelines, for patients with an ischemic stroke in China. METHODS AND RESULTS: The China National Stroke Registry is a prospective cohort study, including 12 416 patients diagnosed with acute ischemic stroke from 132 hospitals across China, for 1 year beginning September 2007. Twelve performance indicators were selected to evaluate the quality of stroke care. Multivariable Cox models were used to determine the association between optimal compliance and clinical outcomes. Conformity with performance measures ranged from a median of 6.5% for the use of intravenous tPA (tissue-type plasminogen activator) to 81.8% for early use of antithrombotics. The optimal compliance with all in-hospital measures was associated with 1-year death after admission (hazard ratio, 0.66; 95% CI, 0.55-0.79). The optimal compliance with all discharge measures was associated with the 1-year death after discharge (hazard ratio, 0.55; 95% CI, 0.44-0.69), 1-year stroke recurrence (hazard ratio, 0.81; 95% CI, 0.70-0.93), and favorable functional outcomes (defined as modified Rankin Scale score of ≤2) (hazard ratio, 1.10; 95% CI, 1.04-1.16). CONCLUSIONS: Adherence to evidence-based ischemic stroke care measures in China revealed substantial gaps, and select measures were associated with improved outcomes. These findings support the need for ongoing quality measurement and improvement in stroke care in China.
A Decade of Improvement in Door-to-Needle Time Among Acute Ischemic Stroke Patients, 2008 to 2017.
Tong X, Wiltz JL, George MG … +6 more , Odom EC, Coleman King SM, Chang T, Yin X, Paul Coverdell National Acute Stroke Program team, Merritt RK
Circ Cardiovasc Qual Outcomes · 2018 Dec · PMID 30557047 · Full text
BACKGROUND: The clinical benefit of intravenous (IV) alteplase in acute ischemic stroke is time dependent. We assessed the overall temporal changes in door-to-needle (DTN) time and examine the factors associated with DTN...
BACKGROUND: The clinical benefit of intravenous (IV) alteplase in acute ischemic stroke is time dependent. We assessed the overall temporal changes in door-to-needle (DTN) time and examine the factors associated with DTN time ≤60 and ≤45 minutes. METHODS AND RESULTS: A total of 496 336 acute ischemic stroke admissions were identified in the Paul Coverdell National Acute Stroke Program from 2008 to 2017. We used generalized estimating equations models to examine the factors associated with DTN time ≤60 and ≤45 minutes, and calculated adjusted odds ratios and 95% CI. Between 2008 and 2017, the percentage of acute ischemic stroke patients who received IV alteplase including those transferred, increased from 6.4% to 15.3%. After excluding those who received IV alteplase at an outside hospital, a total of 39 737 (8%) acute ischemic stroke patients received IV alteplase within 4.5 hours of the time the patient last known to be well. Significant increases were seen in DTN time ≤60 minutes (26.4% in 2008 to 66.2% in 2017, P<0.001), as well as DTN time ≤45 minutes (10.7% in 2008 to 40.5% in 2017, P<0.001). Patients aged 55 to 84 years were more likely to receive IV alteplase within 60 minutes, while those aged 55 to 74 years were more likely to receive IV alteplase within 45 minutes, as compared with those aged 18 to 54 years. Arrival by emergency medical service, and patients with severe stroke were more likely to receive IV alteplase within 60 and 45 minutes. Conversely, women, black patients as compared with white, and patients with a medical history of diseases associated with stroke were less likely to receive DTN time ≤60 or 45 minutes. CONCLUSIONS: Rapid improvements in DTN time were observed in the Paul Coverdell National Acute Stroke Program; however, opportunities to reduce disparities remain.
Impact of Missing Stroke Severity Data on the Accuracy of Hospital Ischemic Stroke Mortality Profiling.
Thompson MP, Luo Z, Gardiner J … +3 more , Burke JF, Nickles A, Reeves MJ
Circ Cardiovasc Qual Outcomes · 2018 Oct · PMID 30354572 · Publisher ↗
BACKGROUND: The Centers for Medicare and Medicaid Services have proposed 30-day ischemic stroke risk-standardized mortality rates that include adjustment for stroke severity using the National Institute of Health Stroke...
BACKGROUND: The Centers for Medicare and Medicaid Services have proposed 30-day ischemic stroke risk-standardized mortality rates that include adjustment for stroke severity using the National Institute of Health Stroke Scale (NIHSS), which is often undocumented. We used simulations to quantify the effect of missing NIHSS data on the accuracy of hospital-level ischemic stroke risk-standardized mortality rate profiling for 100 hypothetical hospitals with different case volumes. METHODS AND RESULTS: We generated simulated data sets of patients with NIHSS scores and other predictors of 30-day mortality based on empirical analysis of data from 7654 patients with ischemic stroke in the Michigan Stroke Registry. We assigned and rank-ordered a true (known) 30-day mortality rate to each hospital in the simulated data sets of N=100 hospitals with either low (100 patients with stroke), medium (300), or high (500) case volumes. We then estimated and rank-ordered 30-day risk-standardized mortality rates for the N=100 hospitals in each simulated data set using hierarchical logistic regression models. In each data set, we systematically varied the rate of missing NIHSS data and whether missing NIHSS data was independent (missing completely at random) or dependent (missing not at random) on the NIHSS score. With no missing NIHSS data, the Spearman correlation between the true hospital performance rank order assigned during data set generation and the estimated 30-day risk-standardized mortality rate rank order was 0.72, 0.88, and 0.91 in low, medium, and high volume hospitals, respectively. However, this fell to as low as 0.50, 0.71, and 0.79 as missing NIHSS data reached 70%. CONCLUSIONS: Missing NIHSS data had substantial detrimental effects on the accuracy of profiling of ischemic stroke mortality, especially in lower volume hospitals. Even with complete NIHSS documentation, significant limitations in ischemic stroke mortality profiling remain.
IL-1 Blockade in Patients With Heart Failure With Preserved Ejection Fraction.
Van Tassell BW, Trankle CR, Canada JM … +13 more , Carbone S, Buckley L, Kadariya D, Del Buono MG, Billingsley H, Wohlford G, Viscusi M, Oddi-Erdle C, Abouzaki NA, Dixon D, Biondi-Zoccai G, Arena R, Abbate A
Circ Heart Fail · 2018 Aug · PMID 30354558 · Full text
Background Enhanced inflammation may lead to exercise intolerance in heart failure with preserved ejection fraction. The aim of the current study was to determine whether IL (interleukin)-1 blockade with anakinra improve...
Background Enhanced inflammation may lead to exercise intolerance in heart failure with preserved ejection fraction. The aim of the current study was to determine whether IL (interleukin)-1 blockade with anakinra improved cardiorespiratory fitness in heart failure with preserved ejection fraction. Methods and Results Thirty-one patients with heart failure with preserved ejection fraction and CRP (C-reactive protein) >2 mg/L were randomized to anakinra (100 mg subcutaneously daily, N=21) or placebo (N=10) for 12 weeks. We measured peak oxygen consumption (Vo), ventilatory efficiency (V/Vco slope), and high-sensitivity CRP and NT-proBNP (N-terminal pro-B-type natriuretic peptide) at 4, 12, and 24 weeks. Twenty-eight patients completed ≥2 visits, 18 women (64%), 27 (96%) obese. There were no differences in peak Vo or V/Vco slope between groups at baseline. Peak Vo was not changed after 12 weeks of anakinra (from 13.6 [11.8-18.0] to 14.2 [11.2-18.5] mL·kg·min, P=0.89), or placebo (14.9 [11.7-17.2] to 15.0 [13.8-16.9] mL·kg·min, P=0.40), without significant between-group differences in changes at 12 weeks (-0.4 [95% CI, -2.2 to +1.4], P=0.64). V/Vco slope was also unchanged with anakinra (from 28.3 [27.2-33.0] to 30.5 [26.3-32.8], P=0.97) or placebo (from 31.6 [27.3-36.9] to 31.2 [27.8-33.4], P=0.78), without significant between-group differences in changes at 12 weeks (+1.2 [95% CI, -1.8 to +4.3], P=0.97). Within the anakinra-treated patients, high-sensitivity CRP and NT-proBNP levels were lower at 4 weeks compared with baseline ( P=0.026 and P=0.022 versus placebo [between-group analysis], respectively). Conclusions Treatment with anakinra for 12 weeks failed to improve peak Vo and V/Vco slope in a group of obese heart failure with preserved ejection fraction patients. The favorable trends in high-sensitivity CRP and NT-proBNP with anakinra deserve exploration in future studies. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02173548.
Rates, Characteristics, and Outcomes of Patients Transferred to Specialized Stroke Centers for Advanced Care.
Ali SF, Fonarow G, Liang L … +4 more , Xian Y, Smith EE, Bhatt DL, Schwamm L
Circ Cardiovasc Qual Outcomes · 2018 Sep · PMID 30354551 · Publisher ↗
Background While many patients are transferred to specialized stroke centers for advanced acute ischemic stroke (AIS) care, few studies have characterized these patients. We sought to determine variation in the rates and...
Background While many patients are transferred to specialized stroke centers for advanced acute ischemic stroke (AIS) care, few studies have characterized these patients. We sought to determine variation in the rates and differences in the baseline characteristics and clinical outcomes between AIS cases presenting directly to stroke centers' front door versus Transfer-Ins from another hospital. Methods and Results We analyzed 970 390 AIS cases in the Get With The Guidelines-Stroke registry from January 2010 to March 2014 to compare hospitals with high Transfer-In rates (≥15%) versus those with low Transfer-In rates (<5%) and to compare the front-door versus Transfer-In patients admitted to those hospitals with high Transfer-In rates (high Transfer-In hospitals). Of 970 390 patients discharged from 1646 hospitals, 87% initially presented via the emergency department versus 13% were a Transfer-In from another hospital. High Transfer-In hospitals had a median 31% Transfer-In rate among all stroke discharges, were larger, had higher annual AIS volume and intravenous tPA (tissue-type plasminogen activator) rates, and were more often Midwest teaching hospitals and stroke centers. Compared with front-door, Transfer-In patients were younger, more often white, had higher median National Institutes of Health Stroke Scale scores, less often hypertension and previous stroke/transient ischemic attack, and higher in-hospital mortality (7.9% versus 4.9%; standardized difference, 12.4%). After multivariable adjustment, Transfer-In patients had higher in-hospital mortality and discharge modified Rankin scale. Conclusions There is significant regional variability in the transfer of patients with AIS. Because Transfer-In patients seem to have worse short-term outcomes, these patients have the potential to negatively influence institutional mortality rates and should be accounted for explicitly in hospital risk-profiling measures.
Psychological Distress and Risk of Myocardial Infarction and Stroke in the 45 and Up Study.
Jackson CA, Sudlow CLM, Mishra GD
Circ Cardiovasc Qual Outcomes · 2018 Sep · PMID 30354546 · Publisher ↗
Background The interplay between mental and physical health remains poorly understood. We investigated whether psychological distress is associated with risk of myocardial infarction (MI) and stroke in a population-based...
Background The interplay between mental and physical health remains poorly understood. We investigated whether psychological distress is associated with risk of myocardial infarction (MI) and stroke in a population-based prospective study. Methods and Results We included participants without prior stroke/MI from the New South Wales 45 and Up Study. We categorized baseline psychological distress as low, medium, and high/very high on the 10-item Kessler Psychological Distress scale and identified stroke and MI through linkage to hospital admission and mortality records. We obtained sex and age-stratified adjusted and unadjusted hazard ratios for the association between psychological distress and MI and stroke. We investigated for interaction between psychological distress and each of age and sex. Among 221 677 participants, 16.2% and 7.3% had moderate and high/very high psychological distress at recruitment, respectively. During 4.7 (±0.98 SD) years of follow-up, 4573 MIs and 2421 strokes occurred. Absolute risk of MI and stroke increased with increasing psychological distress level. In men aged 45 to 79 years, high/very high versus low psychological distress was associated with a 30% increased risk of MI (fully adjusted hazard ratios, 1.30; 95% CI, 1.12-1.51), with weaker estimates in those aged ≥80 years. Among women, high/very high psychological distress was associated with an 18% increased risk of MI (adjusted hazard ratio, 1.18; 95% CI, 0.99-1.42) with similar findings across age groups. In the age group of participants aged 45 to 79 years, high/very high psychological distress and male sex had a supra-additive effect on MI risk. Similar estimates were observed for stroke, with high/very high psychological distress associated with a 24% and 44% increased stroke risk in men and women, respectively, with no evidence of interaction with age or sex. Conclusions Psychological distress has a strong, dose-dependent, positive association with MI and stroke in men and women, despite adjustment for a wide range of confounders.
Incremental Prognostic Value of Right Ventricular Strain in Patients With Acute Decompensated Heart Failure.
Hamada-Harimura Y, Seo Y, Ishizu T … +10 more , Nishi I, Machino-Ohtsuka T, Yamamoto M, Sugano A, Sato K, Sai S, Obara K, Yoshida I, Aonuma K, ICAS-HF Investigators
Circ Cardiovasc Imaging · 2018 Oct · PMID 30354477 · Publisher ↗
BACKGROUND: Although 2-dimensional strain analyses based on speckle tracking echocardiography have been used to detect myocardial deformation, the prognostic impact of 2-dimensional strain is unclear in patients with acu...
BACKGROUND: Although 2-dimensional strain analyses based on speckle tracking echocardiography have been used to detect myocardial deformation, the prognostic impact of 2-dimensional strain is unclear in patients with acute decompensated heart failure (HF). We investigated whether left ventricular and right ventricular (RV) strain parameters assessed by speckle tracking echocardiography provide incremental prognostic information in hospitalized patients because of acute decompensated HF. METHODS AND RESULTS: Six hundred eighteen patients (age, 72±13 years; 38% women; ejection fraction, 46±16%) hospitalized for acute decompensated HF underwent clinical and echocardiographic evaluation just before discharge. We performed strain analyses of left ventricular global longitudinal strain and left ventricular global circumferential strain. We also analyzed RV longitudinal strain only from the free wall (RV-fwLS) and from all segments of the RV global longitudinal strain wall by using Tomtec software. The primary composite end point was cardiovascular death and readmission for HF. There were 34.8% cardiac events during a median follow-up of 427 days. In multivariate Cox models, among echocardiographic parameters, only impaired RV-fwLS (≥-13.1%; hazard ratio, 1.51; 95% CI, 1.12-2.04; P=0.01) was independently associated with cardiac events. Adding RV-fwLS to clinical risk evaluation (age, New York Heart Association class III/IV, blood urea nitrogen, and brain natriuretic peptide) markedly improved prognostic utility and consequently increased net reclassification improvement by 0.30 ( P=0.01). CONCLUSIONS: RV-fwLS is an independent predictor of cardiac events in acute decompensated HF and provides greater prognostic power than standard echocardiographic parameters.
Higher Aortic Stiffness Is Related to Lower Cerebral Blood Flow and Preserved Cerebrovascular Reactivity in Older Adults.
Jefferson AL, Cambronero FE, Liu D … +13 more , Moore EE, Neal JE, Terry JG, Nair S, Pechman KR, Rane S, Davis LT, Gifford KA, Hohman TJ, Bell SP, Wang TJ, Beckman JA, Carr JJ
Circulation · 2018 Oct · PMID 30018169 · Full text
BACKGROUND: Mechanisms underlying the association between age-related arterial stiffening and poor brain health remain elusive. Cerebral blood flow (CBF) homeostasis may be implicated. This study evaluates how aortic sti...
BACKGROUND: Mechanisms underlying the association between age-related arterial stiffening and poor brain health remain elusive. Cerebral blood flow (CBF) homeostasis may be implicated. This study evaluates how aortic stiffening relates to resting CBF and cerebrovascular reactivity (CVR) in older adults. METHODS: Vanderbilt Memory & Aging Project participants free of clinical dementia, stroke, and heart failure were studied, including older adults with normal cognition (n=155; age, 72±7 years; 59% male) or mild cognitive impairment (n=115; age, 73±7 years; 57% male). Aortic pulse wave velocity (PWV; meters per second) was quantified from cardiac magnetic resonance. Resting CBF (milliliters per 100 g per minute) and CVR (CBF response to hypercapnic normoxia stimulus) were quantified from pseudocontinuous arterial spin labeling magnetic resonance imaging. Linear regression models related aortic PWV to regional CBF, adjusting for age, race/ethnicity, education, Framingham Stroke Risk Profile (diabetes mellitus, smoking, left ventricular hypertrophy, prevalent cardiovascular disease, atrial fibrillation), hypertension, body mass index, apolipoprotein E4 ( APOE ε4) status, and regional tissue volume. Models were repeated testing PWV× APOE ε4 interactions. Sensitivity analyses excluded participants with prevalent cardiovascular disease and atrial fibrillation. RESULTS: Among participants with normal cognition, higher aortic PWV related to lower frontal lobe CBF (β=-0.43; P=0.04) and higher CVR in the whole brain (β=0.11; P=0.02), frontal lobes (β=0.12; P<0.05), temporal lobes (β=0.11; P=0.02), and occipital lobes (β=0.14; P=0.01). Among APOE ε4 carriers with normal cognition, findings were more pronounced with higher PWV relating to lower whole-brain CBF (β=-1.16; P=0.047), lower temporal lobe CBF (β=-1.81; P=0.004), and higher temporal lobe CVR (β=0.26; P=0.08), although the last result did not meet the a priori significance threshold. Results were similar in sensitivity models. Among participants with mild cognitive impairment, higher aortic PWV related to lower CBF in the occipital lobe (β=-0.70; P=0.02), but this finding was attenuated when participants with prevalent cardiovascular disease and atrial fibrillation were excluded. Among APOE ε4 carriers with mild cognitive impairment, findings were more pronounced with higher PWV relating to lower temporal lobe CBF (β=-1.20; P=0.02). CONCLUSIONS: Greater aortic stiffening relates to lower regional CBF and higher CVR in cognitively normal older adults, especially among individuals with increased genetic predisposition for Alzheimer's disease. Central arterial stiffening may contribute to reductions in regional CBF despite preserved cerebrovascular reserve capacity.
Effects of Sacubitril/Valsartan Versus Irbesartan in Patients With Chronic Kidney Disease.
Haynes R, Judge PK, Staplin N … +13 more , Herrington WG, Storey BC, Bethel A, Bowman L, Brunskill N, Cockwell P, Hill M, Kalra PA, McMurray JJV, Taal M, Wheeler DC, Landray MJ, Baigent C
Circulation · 2018 Oct · PMID 30002098 · Publisher ↗
BACKGROUND: Sacubitril/valsartan reduces the risk of cardiovascular mortality among patients with heart failure with reduced ejection fraction, but its effects on kidney function and cardiac biomarkers in people with mod...
BACKGROUND: Sacubitril/valsartan reduces the risk of cardiovascular mortality among patients with heart failure with reduced ejection fraction, but its effects on kidney function and cardiac biomarkers in people with moderate to severe chronic kidney disease are unknown. METHODS: The UK HARP-III trial (United Kingdom Heart and Renal Protection-III), a randomized double-blind trial, included 414 participants with an estimated glomerular filtration rate (GFR) 20 to 60 mL/min/1.73 m who were randomly assigned to sacubitril/valsartan 97/103 mg twice daily versus irbesartan 300 mg once daily. The primary outcome was measured GFR at 12 months using ANCOVA with adjustment for each individual's baseline measured GFR. All analyses were by intention to treat. RESULTS: In total, 207 participants were assigned to sacubitril/valsartan and 207 to irbesartan. Baseline measured GFR was 34.0 (SE, 0.8) and 34.7 (SE, 0.8) mL/min/1.73 m, respectively. At 12 months, there was no difference in measured GFR: 29.8 (SE 0.5) among those assigned sacubitril/valsartan versus 29.9 (SE, 0.5) mL/min/1.73 m among those assigned irbesartan; difference, -0.1 (0.7) mL/min/1.73 m. Effects were similar in all prespecified subgroups. There was also no significant difference in estimated GFR at 3, 6, 9, or 12 months and no clear difference in urinary albumin:creatinine ratio between treatment arms (study average difference, -9%; 95% CI, -18 to 1). However, compared with irbesartan, allocation to sacubitril/valsartan reduced study average systolic and diastolic blood pressure by 5.4 (95% CI, 3.4-7.4) and 2.1 (95% CI, 1.0-3.3) mm Hg and levels of troponin I and N terminal of prohormone brain natriuretic peptide (tertiary end points) by 16% (95% CI, 8-23) and 18% (95% CI, 11-25), respectively. The incidence of serious adverse events (29.5% versus 28.5%; rate ratio, 1.07; 95% CI, 0.75-1.53), nonserious adverse reactions (36.7% versus 28.0%; rate ratio, 1.35; 95% CI, 0.96-1.90), and potassium ≥5.5 mmol/L (32% versus 24%, P=0.10) was not significantly different between randomized groups. CONCLUSIONS: Over 12 months, sacubitril/valsartan has similar effects on kidney function and albuminuria to irbesartan, but it has the additional effect of lowering blood pressure and cardiac biomarkers in people with chronic kidney disease. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com . Unique identifier: ISRCTN11958993.
Large-Scale Phenome-Wide Association Study of Variants Demonstrates Protection Against Ischemic Stroke.
Rao AS, Lindholm D, Rivas MA … +3 more , Knowles JW, Montgomery SB, Ingelsson E
Circ Genom Precis Med · 2018 Jul · PMID 29997226 · Full text
BACKGROUND: inhibition is a potent new therapy for hypercholesterolemia and cardiovascular disease. Although short-term clinical trial results have not demonstrated major adverse effects, long-term data will not be avai...
BACKGROUND: inhibition is a potent new therapy for hypercholesterolemia and cardiovascular disease. Although short-term clinical trial results have not demonstrated major adverse effects, long-term data will not be available for some time. Genetic studies in large biobanks offer a unique opportunity to predict drug effects and provide context for the evaluation of future clinical trial outcomes. METHODS: We tested the association of the missense variant rs11591147 with predefined phenotypes and phenome-wide, in 337 536 individuals of British ancestry in the UK Biobank, with independent discovery and replication. Using a Bayesian statistical method, we leveraged phenotype correlations to evaluate the phenome-wide impact of inhibition with higher power at a finer resolution. RESULTS: The T allele of rs11591147 showed a protective effect on hyperlipidemia (odds ratio, 0.63±0.04; =2.32×10), coronary heart disease (odds ratio, 0.73±0.09; =1.05×10), and ischemic stroke (odds ratio, 0.61±0.18; =2.40×10) and was associated with increased type 2 diabetes mellitus risk adjusted for lipid-lowering medication status (odds ratio, 1.24±0.10; =1.98×10). We did not observe associations with cataracts, heart failure, atrial fibrillation, and cognitive dysfunction. Leveraging phenotype correlations, we observed evidence of a protective association with cerebral infarction and vascular occlusion. These results explore the effects of direct inhibition; off-target effects cannot be predicted using this approach. CONCLUSIONS: This result represents the first genetic evidence in a large cohort for the protective effect of inhibition on ischemic stroke and corroborates exploratory evidence from clinical trials. inhibition was not associated with variables other than those related to LDL (low-density lipoprotein) cholesterol, atherosclerosis, and type 2 diabetes mellitus, suggesting that other effects are either small or absent.
Global Burden of Atherosclerotic Cardiovascular Disease in People Living With HIV: Systematic Review and Meta-Analysis.
Shah ASV, Stelzle D, Lee KK … +13 more , Beck EJ, Alam S, Clifford S, Longenecker CT, Strachan F, Bagchi S, Whiteley W, Rajagopalan S, Kottilil S, Nair H, Newby DE, McAllister DA, Mills NL
Circulation · 2018 Sep · PMID 29967196 · Full text
BACKGROUND: With advances in antiretroviral therapy, most deaths in people with HIV are now attributable to noncommunicable illnesses, especially cardiovascular disease. We determine the association between HIV and cardi...
BACKGROUND: With advances in antiretroviral therapy, most deaths in people with HIV are now attributable to noncommunicable illnesses, especially cardiovascular disease. We determine the association between HIV and cardiovascular disease, and estimate the national, regional, and global burden of cardiovascular disease attributable to HIV. METHODS: We conducted a systematic review across 5 databases from inception to August 2016 for longitudinal studies of cardiovascular disease in HIV infection. A random-effects meta-analysis across 80 studies was used to derive the pooled rate and risk of cardiovascular disease in people living with HIV. We then estimated the temporal changes in the population-attributable fraction and disability-adjusted life-years (DALYs) from HIV-associated cardiovascular disease from 1990 to 2015 at a regional and global level. National cardiovascular DALYs associated with HIV for 2015 were derived for 154 of the 193 United Nations member states. The main outcome measure was the pooled estimate of the rate and risk of cardiovascular disease in people living with HIV and the national, regional, and global estimates of DALYs from cardiovascular disease associated with HIV. RESULTS: In 793 635 people living with HIV and a total follow-up of 3.5 million person-years, the crude rate of cardiovascular disease was 61.8 (95% CI, 45.8-83.4) per 10 000 person-years. In comparison with individuals without HIV, the risk ratio for cardiovascular disease was 2.16 (95% CI, 1.68-2.77). Over the past 26 years, the global population-attributable fraction from cardiovascular disease attributable to HIV increased from 0.36% (95% CI, 0.21%-0.56%) to 0.92% (95% CI, 0.55%-1.41%), and DALYs increased from 0.74 (95% CI, 0.44-1.16) to 2.57 (95% CI, 1.53-3.92) million. There was marked regional variation with most DALYs lost in sub-Saharan Africa (0.87 million, 95% CI, 0.43-1.70) and the Asia Pacific (0.39 million, 95% CI, 0.23-0.62) regions. The highest population-attributable fraction and burden were observed in Swaziland, Botswana, and Lesotho. CONCLUSIONS: People living with HIV are twice as likely to develop cardiovascular disease. The global burden of HIV-associated cardiovascular disease has tripled over the past 2 decades and is now responsible for 2.6 million DALYs per annum with the greatest impact in sub-Saharan Africa and the Asia Pacific regions. CLINICAL TRIAL REGISTRATION: URL: https://www.crd.york.ac.uk/prospero . Unique identifier: CRD42016048257.
CAABL-AF (California Study of Ablation for Atrial Fibrillation): Mortality and Stroke, 2005 to 2013.
Srivatsa UN, Danielsen B, Amsterdam EA … +6 more , Pezeshkian N, Yang Y, Nordsieck E, Fan D, Chiamvimonvat N, White RH
Circ Arrhythm Electrophysiol · 2018 Jun · PMID 29884619 · Publisher ↗
BACKGROUND: Ablation for atrial fibrillation (AF) is superior to medical therapy for rhythm control. We compared stroke and mortality among patients undergoing ablation for AF to matched controls in a large multiethnic p...
BACKGROUND: Ablation for atrial fibrillation (AF) is superior to medical therapy for rhythm control. We compared stroke and mortality among patients undergoing ablation for AF to matched controls in a large multiethnic population. METHODS: Using discharge and surgical records from California nonfederal hospitals, we identified patients who had ablation and principal diagnosis of AF with at least 1 prior hospitalization for AF. We excluded cases with valve disease, open maze, other arrhythmias, or implantable devices. Matched controls were selected based on years of AF diagnosis, age, sex, and being alive the same number of days from the initial AF encounter to the ablation date. Clinical outcomes, including mortality, ischemic stroke, or hemorrhagic stroke, were assessed using a weighted proportional hazard model, adjusting for demographics, prior admissions with AF before the ablation, calendar year, and presence of chronic comorbidities. RESULTS: There were 4169 ablation cases and 4169 weighted-matched controls; 39% percent of the ablation group was >65 years, 72% men, 84% white; mean follow-up was up to 3.6±0.9 years. In adjusted models, ablation was associated with significantly lower mortality (per patient-years) 0.9% versus 1.9%, hazard ratio=0.59 (<0.0001; confidence interval: 0.45-0.77); ischemic stroke (>30 days post-ablation ≤5 years), 0.37% versus 0.59%, hazard ratio=0.68 (=0.04; confidence interval: 0.47-0.97); hemorrhagic stroke 0.11% versus 0.35%, hazard ratio=0.36 (=0.001; confidence interval: 0.20-0.64) compared with controls. CONCLUSIONS: In this large population-based study of hospitalized patients with nonvalvular AF, ablation was associated with lower mortality, ischemic stroke, and hemorrhagic stroke compared with controls.
Use of Biomarkers to Predict Specific Causes of Death in Patients With Atrial Fibrillation.
Sharma A, Hijazi Z, Andersson U … +11 more , Al-Khatib SM, Lopes RD, Alexander JH, Held C, Hylek EM, Leonardi S, Hanna M, Ezekowitz JA, Siegbahn A, Granger CB, Wallentin L
Circulation · 2018 Oct · PMID 29871978 · Publisher ↗
BACKGROUND: Atrial fibrillation is associated with an increased risk of death. High-sensitivity troponin T, growth differentiation factor-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and interleukin-6 level...
BACKGROUND: Atrial fibrillation is associated with an increased risk of death. High-sensitivity troponin T, growth differentiation factor-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and interleukin-6 levels are predictive of cardiovascular events and total cardiovascular death in anticoagulated patients with atrial fibrillation. The prognostic utility of these biomarkers for cause-specific death is unknown. METHODS: The ARISTOTLE trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients (1.9 years median follow-up). Cox models were used to identify clinical variables and biomarkers independently associated with each specific cause of death. RESULTS: In total, 1272 patients died: 652 (51%) cardiovascular, 32 (3%) bleeding, and 588 (46%) noncardiovascular/nonbleeding deaths. Among cardiovascular deaths, 255 (39%) were sudden cardiac deaths, 168 (26%) heart failure deaths, and 106 (16%) stroke/systemic embolism deaths. Biomarkers were the strongest predictors of cause-specific death: a doubling of troponin T was most strongly associated with sudden death (hazard ratio [HR], 1.48; P<0.001), NT-proBNP with heart failure death (HR, 1.62; P<0.001), and growth differentiation factor-15 with bleeding death (HR, 1.72; P=0.028). Prior stroke/systemic embolism (HR, 2.58; P>0.001) followed by troponin T (HR, 1.45; P<0.0029) were the most predictive for stroke/ systemic embolism death. Adding all biomarkers to clinical variables improved discrimination for each cause-specific death. CONCLUSIONS: Biomarkers were some of the strongest predictors of cause-specific death and may improve the ability to discriminate among patients' risks for different causes of death. These data suggest a potential role of biomarkers for the identification of patients at risk for different causes of death in patients anticoagulated for atrial fibrillation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00412984.
Comparison of Acute Ischemic Stroke Care and Outcomes Between Comprehensive Stroke Centers and Primary Stroke Centers in the United States.
Man S, Zhao X, Uchino K … +8 more , Hussain MS, Smith EE, Bhatt DL, Xian Y, Schwamm LH, Shah S, Khan Y, Fonarow GC
Circ Cardiovasc Qual Outcomes · 2018 Jun · PMID 29794035 · Full text
BACKGROUND: To improve stroke care, the Brain Attack Coalition recommended establishing primary stroke center (PSC) and comprehensive stroke center (CSC) certification. This study aimed to compare ischemic stroke care an...
BACKGROUND: To improve stroke care, the Brain Attack Coalition recommended establishing primary stroke center (PSC) and comprehensive stroke center (CSC) certification. This study aimed to compare ischemic stroke care and in-hospital outcomes between CSCs and PSCs. METHODS AND RESULTS: We analyzed patients with acute ischemic stroke who were hospitalized at stroke centers participating in Get With The Guidelines-Stroke from 2013 to 2015. Multivariable logistic regression models were generated to examine the association between stroke center certification (CSC versus PSC) and performances and outcomes. This study included 722 941 patients who were admitted to 134 CSCs and 1047 PSCs. Both CSCs and PSCs had good conformity to 7 performance measures and the summary defect-free care measure. Among emergency department admissions, CSCs had higher intravenous tPA (tissue-type plasminogen activator) and endovascular thrombectomy rates than PSCs (14.3% versus 10.3%, 4.1% versus 1.0%, respectively). Door to intravenous tPA time was shorter at CSCs (median, 52 versus 61 minutes; adjusted risk ratio, 0.92; 95% confidence interval, 0.89-0.95). More patients at CSCs had door to intravenous tPA time ≤60 minutes (79.7% versus 65.1%; adjusted odds ratio, 1.48; 95% confidence interval, 1.25-1.75). For transferred patients, CSCs and PSCs had comparable overall performance in defect-free care, except higher endovascular thrombectomy therapy rates. The overall in-hospital mortality was higher at CSCs in both emergency department admissions (4.6% versus 3.8%; adjusted odds ratio, 1.14; 95% confidence interval, 1.01-1.29) and transferred patients (7.7% versus 6.8%; adjusted odds ratio, 1.17; 95% confidence interval, 1.05-1.32). In-hospital outcomes were comparable between CSCs and PSCs in patients who received intravenous tPA or endovascular thrombectomy. CONCLUSIONS: CSCs and PSCs achieved similar overall care quality for patients with acute ischemic stroke. CSCs exceeded PSCs in timely acute reperfusion therapy for emergency department admissions, whereas PSCs had lower risk-adjusted in-hospital mortality. This information may be important for acute stroke triage and targeted quality improvement.
High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD): A Randomized Superiority Trial.
Taguchi I, Iimuro S, Iwata H … +38 more , Takashima H, Abe M, Amiya E, Ogawa T, Ozaki Y, Sakuma I, Nakagawa Y, Hibi K, Hiro T, Fukumoto Y, Hokimoto S, Miyauchi K, Yamazaki T, Ito H, Otsuji Y, Kimura K, Takahashi J, Hirayama A, Yokoi H, Kitagawa K, Urabe T, Okada Y, Terayama Y, Toyoda K, Nagao T, Matsumoto M, Ohashi Y, Kaneko T, Fujita R, Ohtsu H, Ogawa H, Daida H, Shimokawa H, Saito Y, Kimura T, Inoue T, Matsuzaki M, Nagai R
Circulation · 2018 May · PMID 29735587 · Full text
BACKGROUND: Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous "more versus less statins" trials. However, no clear evidence for more versus...
BACKGROUND: Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous "more versus less statins" trials. However, no clear evidence for more versus less statins has been established in an Asian population. METHODS: In this prospective, multicenter, randomized, open-label, blinded end point study, 13 054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) <120 mg/dL during a run-in period (pitavastatin 1 mg/d) were randomized in a 1-to-1 fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention. RESULTS: The mean age of the study population was 68 years, and 83% were male. The mean LDL-C level before enrollment was 93 mg/dL with 91% of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/dL than in the low-dose group (<0.001). With a median follow-up of 3.9 years, high-dose as compared with low-dose pitavastatin significantly reduced the risk of the primary end point (266 patients [4.3%] and 334 patients [5.4%]; hazard ratio, 0.81; 95% confidence interval, 0.69-0.95; =0.01) and the risk of the secondary composite end point (489 patients [7.9%] and 600 patients [9.7%]; hazard ratio, 0.83; 95% confidence interval, 0.73-0.93; =0.002). High-dose pitavastatin also significantly reduced the risks of several other secondary end points such as all-cause death, myocardial infarction, and clinically indicated coronary revascularization. The results for the primary and the secondary composite end points were consistent across several prespecified subgroups, including the low (<95 mg/dL) baseline LDL-C subgroup. Serious adverse event rates were low in both groups. CONCLUSIONS: High-dose (4 mg/d) compared with low-dose (1 mg/d) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01042730.
Patent Foramen Ovale Closure: The Pendulum Swings.
Hankey GJ, McQuillan BM
Circulation · 2018 May · PMID 29735585 · Publisher ↗
Abstract loading — click title to view on PubMed.
Indications for the Performance of Intracranial Endovascular Neurointerventional Procedures: A Scientific Statement From the American Heart Association.
Eskey CJ, Meyers PM, Nguyen TN … +11 more , Ansari SA, Jayaraman M, McDougall CG, DeMarco JK, Gray WA, Hess DC, Higashida RT, Pandey DK, Peña C, Schumacher HC, American Heart Association Council on Cardiovascular Radiology and Intervention and Stroke Council
Circulation · 2018 May · PMID 29674324 · Publisher ↗
Intracranial endovascular interventions provide effective and minimally invasive treatment of a broad spectrum of diseases. This area of expertise has continued to gain both wider application and greater depth as new and...
Intracranial endovascular interventions provide effective and minimally invasive treatment of a broad spectrum of diseases. This area of expertise has continued to gain both wider application and greater depth as new and better techniques are developed and as landmark clinical studies are performed to guide their use. Some of the greatest advances since the last American Heart Association scientific statement on this topic have been made in the treatment of ischemic stroke from large intracranial vessel occlusion, with more effective devices and large randomized clinical trials showing striking therapeutic benefit. The treatment of cerebral aneurysms has also seen substantial evolution, increasing the number of aneurysms that can be treated successfully with minimally invasive therapy. Endovascular therapies for such other diseases as arteriovenous malformations, dural arteriovenous fistulas, idiopathic intracranial hypertension, venous thrombosis, and neoplasms continue to improve. The purpose of the present document is to review current information on the efficacy and safety of procedures used for intracranial endovascular interventional treatment of cerebrovascular diseases and to summarize key aspects of best practice.
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