Filtering directory lookups in CMPs

Coherence protocols consume an important fraction of power to determine which coherence action should take place. In this paper we focus on CMPs with a shared cache and a directory-based coherence protocol implemented as a duplicate of local caches tags. We observe that a big fraction of directory lookups produce a miss since the block looked up is not cached in any local cache. We propose to add a filter before the directory lookup in order to reduce the number of lookups to this structure. The filter identifies whether the current block was last accessed as a data or as an instruction. With this information, looking up the whole directory can be avoided for most accesses. We evaluate the filter in a CMP with 8 in-order processors with 4 threads each and a memory hierarchy with a shared L2 cache.We show that a filter with a size of 3% of the tag array of the shared cache can avoid more than 70% of all comparisons performed by directory lookups with a performance loss of just 0.2% for SPLASH2 and 1.5% for Specweb2005. On average, the number of 15-bit comparisons avoided per cycle is 54 out of 77 for SPLASH2 and 29 out of 41 for Specweb2005. In both cases, the filter requires less than one read of 1 bit per cycle.Postprint (published version

Filtering directory lookups in CMPs

Coherence protocols consume an important fraction of power to determine which coherence action should take place. In this paper we focus on CMPs with a shared cache and a directory-based coherence protocol implemented as a duplicate of local caches tags. We observe that a big fraction of directory lookups produce a miss since the block looked up is not cached in any local cache. We propose to add a filter before the directory lookup in order to reduce the number of lookups to this structure. The filter identifies whether the current block was last accessed as a data or as an instruction. With this information, looking up the whole directory can be avoided for most accesses. We evaluate the filter in a CMP with 8 in-order processors with 4 threads each and a memory hierarchy with a shared L2 cache.We show that a filter with a size of 3% of the tag array of the shared cache can avoid more than 70% of all comparisons performed by directory lookups with a performance loss of just 0.2% for SPLASH2 and 1.5% for Specweb2005. On average, the number of 15-bit comparisons avoided per cycle is 54 out of 77 for SPLASH2 and 29 out of 41 for Specweb2005. In both cases, the filter requires less than one read of 1 bit per cycle

Combining glucose and high-sensitivity cardiac troponin in the early diagnosis of acute myocardial infarction

Abstract Glucose is a universally available inexpensive biomarker, which is increased as part of the physiological stress response to acute myocardial infarction (AMI) and may therefore help in its early diagnosis. To test this hypothesis, glucose, high-sensitivity cardiac troponin (hs-cTn) T, and hs-cTnI were measured in consecutive patients presenting with acute chest discomfort to the emergency department (ED) and enrolled in a large international diagnostic study (NCT00470587). Two independent cardiologists centrally adjudicated the final diagnosis using all clinical data, including serial hs-cTnT measurements, cardiac imaging and clinical follow-up. The primary diagnostic endpoint was index non-ST-segment elevation MI (NSTEMI). Prognostic endpoints were all-cause death, and cardiovascular (CV) death or future AMI, all within 730-days. Among 5639 eligible patients, NSTEMI was the adjudicated final diagnosis in 1051 (18.6%) patients. Diagnostic accuracy quantified using the area under the receiver-operating characteristics curve (AUC) for the combination of glucose with hs-cTnT and glucose with hs-cTnI was very high, but not higher versus that of hs-cTn alone (glucose/hs-cTnT 0.930 [95% CI 0.922–0.937] versus hs-cTnT 0.929 [95% CI 0.922–0.937]; glucose/hs-cTnI 0.944 [95% CI 0.937–0.951] versus hs-cTnI 0.944 [95% CI 0.937–0.951]). In early-presenters, a dual-marker strategy (glucose < 7 mmol/L and hs-cTnT < 5/hs-cTnI < 4 ng/L) provided very high and comparable sensitivity to slightly lower hs-cTn concentrations (cTnT/I < 4/3 ng/L) alone, and possibly even higher efficacy. Glucose was an independent predictor of 730-days endpoints. Our results showed that a dual marker strategy of glucose and hs-cTn did not increase the diagnostic accuracy when used continuously. However, a cutoff approach combining glucose and hs-cTn may provide diagnostic utility for patients presenting ≤ 3 h after onset of symptoms, also providing important prognostic information

Influence of Meteorological Temperature and Pressure on the Severity of Heart Failure Decompensations

To investigate the relationship between ambient temperature and atmospheric pressure (AP) and the severity of heart failure (HF) decompensations.; We analysed patients coming from the Epidemioloy Acute Heart Failure Emergency (EAHFE) Registry, a multicentre prospective cohort study enrolling patients diagnosed with decompensated HF in 26 emergency departments (EDs) of 16 Spanish cities. We recorded patient and demographic data and maximum temperature (T; max; ) and AP (AP; max; ) the day before ED consultation. Associations between temperature and AP and severity endpoints were explored by logistic regression. We used restricted cubic splines to model continuous non-linear associations of temperature and AP with each endpoint.; We analysed 16,545 patients. Daily T; max; and AP; max; (anomaly) of the day before patient ED arrival ranged from 0.8 to 41.6° and from - 61.7 to 69.9 hPa, respectively. A total of 12,352 patients (75.2%) were hospitalised, with in-hospital mortality in 1171 (7.1%). The probability of hospitalisation by HF decompensation showed a U-shaped curve versus T; max; and an increasing trend versus AP; max; . Regarding temperature, hospitalisation significantly increased from 20 °C (reference) upwards (25 °C: OR = 1.12, 95% CI = 1.04-1.21; 40 °C: 1.65, 1.13-2.40) and below 5.4 °C (5 °C: 1.21, 1.01-1.46). Concerning the mean AP of the city (anomaly = 0 hPa), hospitalisation increased when AP; max; (anomaly) was above + 7.0 hPa (atmospheric anticyclone; + 10 hPa: 1.14, 1.05-1.24; + 30 hPa: 2.02. 1.35-3.03). The lowest probability of mortality also corresponded to cold-mild temperatures and low AP, with a significant increased risk only found for T; max; above 24.3 °C (25 °C: 1.13, 1.01-1.27; 40 °C: 2.05, 1.15-3.64) and AP; max; (anomaly) above + 3.4 hPa (+ 10 hPa: 1.21, 1.07-1.36; + 30 hPa: 1.73, 1.06-2.81). Sensitivity analysis confirmed the main analysis results.; Temperature and AP are independently associated with the severity of HF decompensations, with possible different effects on the need for hospitalisation and in-hospital mortality

Characteristics and Outcomes of Type 2 Myocardial Infarction

In contrast to type 1 myocardial infarction (T1MI) caused by atherothrombosis, characteristics and outcomes of type 2 myocardial infarction (T2MI) caused by supply-demand mismatch are incompletely understood.; To explore the characteristics and outcomes of patients with T2MI compared with those with T1MI.; In a prospective, international, multicenter cohort study including 12 emergency departments (EDs) in 5 European countries, unselected patients presenting with acute chest discomfort were enrolled from April 2006 to April 2018. Follow-up was done by telephone or in written form 3, 12, and 24 months after hospital discharge. Data were analyzed from April 2006 to April 2020.; The final diagnoses of T2MI and T1MI were centrally adjudicated according to the Fourth Universal Definition of Myocardial Infarction by 2 independent cardiologists, including the pathophysiological trigger of T2MI.; Patient characteristics and outcomes, including 2-year all-cause and cardiovascular mortality and future T2MI and T1MI events.; Of 6253 included patients, 2078 (33.2%) were women, and the median (IQR) age was 61 (48-74) years. Among 6253 patients with acute chest discomfort, the final adjudicated diagnosis was T2MI in 251 patients (4.0%), with tachyarrhythmia and hypertension responsible for two-thirds of cases, and T1MI in 1027 patients (16.4%). All-cause and cardiovascular mortality were comparable at 2 years (T2MI: adjusted hazard ratio, 1.0; 95% CI, 0.7-1.5; T1MI: adjusted hazard ratio, 0.7; 95% CI, 0.4-1.1). Patients with tachyarrhythmia or hypertension as their underlying trigger of T2MI had a lower mortality compared with patients with hypotension, hypoxemia, or anemia. Future T2MI was more likely among patients with index T2MI compared with patients with index T1MI (hazard ratio, 3.2; 95% CI, 1.4-7.5). Similarly, future T1MI was more likely to occur among patients with index T1MI (hazard ratio, 3.0; 95% CI, 1.2-7.4).; Among patients with T2MI, tachyarrhythmia and hypertension were responsible for more than two-thirds of T2MI cases. While T2MI and T1MI had comparable all-cause and cardiovascular mortality at 2 years, patients with tachyarrhythmia or hypertension as their underlying trigger of T2MI had a lower mortality compared with patients with hypotension, hypoxemia, or anemia. Future T2MI occurred 3-fold more frequently among patients with T2MI vs T1MI as the index event. Improved understanding of the specifics of patients with T2MI should help improve management strategies

Characteristics and Outcomes of Type 2 Myocardial Infarction

Importance: In contrast to type 1 myocardial infarction (T1MI) caused by atherothrombosis, characteristics and outcomes of type 2 myocardial infarction (T2MI) caused by supply-demand mismatch are incompletely understood. Objective: To explore the characteristics and outcomes of patients with T2MI compared with those with T1MI. Design, Setting, and Participants: In a prospective, international, multicenter cohort study including 12 emergency departments (EDs) in 5 European countries, unselected patients presenting with acute chest discomfort were enrolled from April 2006 to April 2018. Follow-up was done by telephone or in written form 3, 12, and 24 months after hospital discharge. Data were analyzed from April 2006 to April 2020. Interventions: The final diagnoses of T2MI and T1MI were centrally adjudicated according to the Fourth Universal Definition of Myocardial Infarction by 2 independent cardiologists, including the pathophysiological trigger of T2MI. Main Outcomes and Measures: Patient characteristics and outcomes, including 2-year all-cause and cardiovascular mortality and future T2MI and T1MI events. Results: Of 6253 included patients, 2078 (33.2%) were women, and the median (IQR) age was 61 (48-74) years. Among 6253 patients with acute chest discomfort, the final adjudicated diagnosis was T2MI in 251 patients (4.0%), with tachyarrhythmia and hypertension responsible for two-thirds of cases, and T1MI in 1027 patients (16.4%). All-cause and cardiovascular mortality were comparable at 2 years (T2MI: adjusted hazard ratio, 1.0; 95% CI, 0.7-1.5; T1MI: adjusted hazard ratio, 0.7; 95% CI, 0.4-1.1). Patients with tachyarrhythmia or hypertension as their underlying trigger of T2MI had a lower mortality compared with patients with hypotension, hypoxemia, or anemia. Future T2MI was more likely among patients with index T2MI compared with patients with index T1MI (hazard ratio, 3.2; 95% CI, 1.4-7.5). Similarly, future T1MI was more likely to occur among patients with index T1MI (hazard ratio, 3.0; 95% CI, 1.2-7.4). Conclusions and Relevance: Among patients with T2MI, tachyarrhythmia and hypertension were responsible for more than two-thirds of T2MI cases. While T2MI and T1MI had comparable all-cause and cardiovascular mortality at 2 years, patients with tachyarrhythmia or hypertension as their underlying trigger of T2MI had a lower mortality compared with patients with hypotension, hypoxemia, or anemia. Future T2MI occurred 3-fold more frequently among patients with T2MI vs T1MI as the index event. Improved understanding of the specifics of patients with T2MI should help improve management strategies

Cardiovascular Biomarkers in the Early Discrimination of Type 2 Myocardial Infarction.

Importance Rapid and accurate noninvasive discrimination of type 2 myocardial infarction (T2MI), which is because of a supply-demand mismatch, from type 1 myocardial infarction (T1MI), which arises via plaque rupture, is essential, because treatment differs substantially. Unfortunately, this is a major unmet clinical need, because even high-sensitivity cardiac troponin (hs-cTn) measurement provides only modest accuracy. Objective To test the hypothesis that novel cardiovascular biomarkers quantifying different pathophysiological pathways involved in T2MI and/or T1MI may aid physicians in the rapid discrimination of T2MI vs T1MI. Design, Setting, and Participants This international, multicenter prospective diagnostic study was conducted in 12 emergency departments in 5 countries (Switzerland, Spain, Italy, Poland, and the Czech Republic) with patients presenting with acute chest discomfort to the emergency departments. The study quantified the discrimination of hs-cTn T, hs-cTn I, and 17 novel cardiovascular biomarkers measured in subsets of consecutively enrolled patients against a reference standard (final diagnosis), centrally adjudicated by 2 independent cardiologists according to the fourth universal definition of MI, using all information, including cardiac imaging and serial measurements of hs-cTnT or hs-cTnI. Results Among 5887 patients, 1106 (18.8%) had an adjudicated final diagnosis of MI; of these, 860 patients (77.8%) had T1MI, and 246 patients (22.2%) had T2MI. Patients with T2MI vs those with T1MI had lower concentrations of biomarkers quantifying cardiomyocyte injury hs-cTnT (median [interquartile range (IQR)], 30 (17-55) ng/L vs 58 (28-150) ng/L), hs-cTnI (median [IQR], 23 [10-83] ng/L vs 115 [28-576] ng/L; P < .001), and cardiac myosin-binding protein C (at presentation: median [IQR], 76 [38-189] ng/L vs 257 [75-876] ng/L; P < .001) but higher concentrations of biomarkers quantifying endothelial dysfunction, microvascular dysfunction, and/or hemodynamic stress (median [IQR] values: C-terminal proendothelin 1, 97 [75-134] pmol/L vs 68 [55-91] pmol/L; midregional proadrenomedullin, 0.97 [0.67-1.51] pmol/L vs 0.72 [0.53-0.99] pmol/L; midregional pro-A-type natriuretic peptide, 378 [207-491] pmol/L vs 152 [90-247] pmol/L; and growth differentiation factor 15, 2.26 [1.44-4.35] vs 1.56 [1.02-2.19] ng/L; all P < .001). Discrimination for these biomarkers, as quantified by the area under the receiver operating characteristics curve, was modest (hs-cTnT, 0.67 [95% CI, 0.64-0.71]; hs-cTn I, 0.71 [95% CI, 0.67-0.74]; cardiac myosin-binding protein C, 0.67 [95% CI, 0.61-0.73]; C-terminal proendothelin 1, 0.73 [95% CI, 0.63-0.83]; midregional proadrenomedullin, 0.66 [95% CI, 0.60-0.73]; midregional pro-A-type natriuretic peptide, 0.77 [95% CI, 0.68-0.87]; and growth differentiation factor 15, 0.68 [95% CI, 0.58-0.79]). Conclusions and Relevance In this study, biomarkers quantifying myocardial injury, endothelial dysfunction, microvascular dysfunction, and/or hemodynamic stress provided modest discrimination in early, noninvasive diagnosis of T2MI

Ambient temperature and atmospheric pressure at discharge as precipitating factors in immediate adverse events in patients treated for decompensated heart failure

To investigate the relationship of ambient temperature and atmospheric pressure (AP) at patient discharge after an episode of acute heart failure (AHF) with very early post-discharge adverse outcomes. We analyzed 14,656 patients discharged after an AHF episode from 26 hospitals in 16 Spanish cities. The primary outcome was the 7-day post-discharge combined adverse event (emergency department -ED- revisit or hospitalization due to AHF, or all-cause death), and secondary outcomes were these three adverse events considered individually. Associations (adjusted for patient and demographic conditions, and length of stay -LOS- during the AHF index episode) of temperature and AP with the primary and secondary outcomes were investigated. We used restricted cubic splines to model the continuous non-linear association of temperature and AP with each endpoint. Some sensitivity analyses were performed. Patients were discharged after a median LOS of 5 days (IQR = 1-10). The highest temperature at discharge ranged from - 2 to 41.6 °C, and AP was from 892 to 1037 hPa. The 7-day post-discharge combined event occurred in 1242 patients (8.4%), with percentages of 7-day ED-revisit, hospitalization and death of 7.8%, 5.1% and 0.9%, respectively. We found no association between the maximal temperature and AP on the day of discharge and the primary or secondary outcomes. Similarly, there were no significant associations when the analyses were restricted to hospitalized patients (median LOS = 7 days, IQR = 4-11) during the index event, or when lag-1, lag-2 or the mean of the 3 post-discharge days (instead of point estimation) of ambient temperature and AP were considered. Temperature and AP on the day of patient discharge are not independently associated with the risk of very early adverse events during the vulnerable post-discharge period in patients discharged after an AHF episode