Silent Infarction Research Articles

Initial Progressions of Carotid Artery Plaque Are Associated with Risk Factors of Cardiovascular Disease.

Background:Carotid artery plaque, white matter disease (WMD), and silent lacunae infarcts (initial indicators) are associated with symptomatic cerebral infarction (CI) caused by atherosclerosis. We retrospectively examined the association between the initial indicators and risk factors for cerebrovascular disease, considering the primary prevention of symptomatic CI.Methods:We divided 1503 individuals who were neurologically healthy and enrolled in a brain screening program (brain dock) at our institution, into three initial plaque grades (grade 0, 1, and 2) based on having no plaques, having plaques on the right or left carotid artery, or having plaques on both carotid arteries, respectively. We analyzed the risk factors according to the presence/absence of the initial indicators.Results:WMD and the risk factors (low-density lipoprotein [LDL], hemoglobin A1c, systolic blood pressure [BP], and smoking cigarettes) were positively correlated with the initial plaque grades, even when their laboratory values were within normal ranges. Systolic BP (116.5 ± 14.0 mmHg) was significantly lower in group 00 (without carotid plaque and WMD) than that in age-adjusted others (with carotid plaque or WMD). In young participants aged between 40 and 52 years, LDL (132.8 ± 24.5 mg/dl) was significantly higher in subgroup ++ (with carotid plaque and WMD) compared to others (without carotid plaque or WMD).Conclusion:Initial plaque grade and WMD grade as clinical initial indicators of symptomatic CI are associated with risk factors. To avoid deterioration of the initial indicators, it was suggested that the risk factors should be maintained at the lower ends of normal ranges and smoking cessation should be recommended.

A Study of Cardiac Autonomic Neuropathy Among Type-II Diabetic Patients

Background: Though very common, CAN is a least understood complication of diabetes which is often under diagnosed. In diabetes mellitus patients, CAN leads to silent myocardial infarction and sudden death. So by identifying CAN early, which is asymptomatic will help to delay or arrest its progression. AIM: To find out the prevalence and the associated risk factors of Cardiac autonomic neuropathy (CAN) among type-II Diabetes Mellitus patients in a tertiary care hospital. Materials & Methods: A total of 273 type-II diabetic participants were selected after taking into consideration of inclusion & exclusion criteria. The prevalence of CAN was assessed by ewings and clarkesnon invasive cardiac autonomic neuropathy reflex tests. The association of risk factors with the presence of CAN was analysed by using Pearson’s chi square test. Data were analysed by using SPSS 16. The accepted level of significance was set below 0.05 (P<0.05). Results: The prevalence of CAN among type-II diabetic patients in this study was found to be 34%. Prevalence of CAN increased in the participants with male gender, increased age, and increased BMI, increased duration of diabetes, poor glycaemic control,dyslipidimea, smokers and hypertension and it is statistically significant. Conclusion: In this study it is observed that the prevalence of CAN increased with old age, male gender, poor glycemic control, increased duration of diabetes, Dyslipidemia, higher BMI, Hypertension & smoking. So risk factors associated with the CAN be detected and treated at an early stage to further reduce morbidity and mortality.

Screening Cardiovascular Autonomic Neuropathy in Diabetic Patients With Microvascular Complications Using Machine Learning: A 24-Hour Heart Rate Variability Study

Cardiovascular autonomic neuropathy (CAN) is one of the most overlooked complications associated with diabetes. It is characterized by damage in the autonomic nerves regulating heart rate and vascular compliance. Ewing battery is currently the diagnostic tool of choice but is unable to detect sub-clinical CAN and requires patient cooperation. In addition, appropriate timing (day/night) of CAN diagnostic test was not explored in the past. Therefore, a novel approach is proposed herein to investigate the feasibility of using heart rate variability (HRV) features over 24 hours embedded within machine learning algorithms to provide a complete screening for patients suffering from CAN. 24-hour Holter ECG data were acquired from a Bangladeshi cohort (n = 95 patients [75 Diabetic and 25 healthy]). HRV features were extracted from every 5-minute segment of the HRV signal and used as input to four machine learning algorithms for hourly training and testing. A complete hierarchical step by step diagnosis procedure (4 tests) was developed; namely test 1 to check for being healthy or diabetic; test 2 to check for any microvascular complications (including neuropathy such as CAN, peripheral neuropathy (DPN), nephropathy (NEP), and retinopathy (RET)) or not; test 3 to check for presence of only CAN; test 4 to check for combined or multiple complications along with CAN. The highest levels of performance were achieved with accuracy measures of 85.5% (test 1 - convolutional neural network (CNN)), 98.5% (test 2 - CNN), 98.3% (test 3 - one-class support vector machines (SVM)), and 90.9% (test 4 - random forest). Hours 7:00 AM and 7:00 PM were found to be most significant in the diagnosis of CAN in diabetic patients (test 1, 3, and 4). Early screening of CAN by our proposed models could help primary healthcare centers stratify the risk leading to early treatment in preventing sudden cardiac death due to silent myocardial infarction. The approach is considered to be simple and effective, especially for under-resourced clinical settings.

Association Between Silent Myocardial Infarction and Long-Term Risk of Sudden Cardiac Death.

BackgroundAlthough silent myocardial infarction (SMI) is prognostically important, the risk of sudden cardiac death (SCD) among patients with incident SMI is not well established.Methods and ResultsWe examined 2 community‐based cohorts: the ARIC (Atherosclerosis Risk in Communities) study (n=13 725) and the CHS (Cardiovascular Health Study) (n=5207). Incident SMI was defined as electrocardiographic evidence of new myocardial infarction during follow‐up visits that was not present at the baseline. The primary study end point was physician‐adjudicated SCD. In the ARIC study, 513 SMIs, 441 clinically recognized myocardial infarctions (CMIs), and 527 SCD events occurred during a median follow‐up of 25.4 years. The multivariable hazard ratios of SMI and CMI for SCD were 5.20 (95% CI, 3.81–7.10) and 3.80 (95% CI, 2.76–5.23), respectively. In the CHS, 1070 SMIs, 632 CMIs, and 526 SCD events occurred during a median follow‐up of 12.1 years. The multivariable hazard ratios of SMI and CMI for SCD were 1.70 (95% CI, 1.32–2.19) and 4.08 (95% CI, 3.29–5.06), respectively. The pooled hazard ratios of SMI and CMI for SCD were 2.65 (2.18–3.23) and 3.99 (3.34–4.77), respectively. The risk of SCD associated with SMI is stronger with White individuals, men, and younger age. The population‐attributable fraction of SCD was 11.1% for SMI, and SMI was associated with an absolute risk increase of 8.9 SCDs per 1000 person‐years. Addition of SMI significantly improved the predictive power for both SCD and non‐SCD.ConclusionsIncident SMI is independently associated with an increased risk of SCD in the general population. Additional research should address screening for SMI and the role of standard post–myocardial infarction therapy.

Hippocampal silent infarct leads to subtle cognitive decline that is associated with inflammation and gliosis at twenty-four hours after injury in a rat model

Silent infarcts (SI) are subcortical cerebral infarcts that occur in the absence of clinical symptoms commonly associated with ischemia and are linked to dementia development. Little is known about the pathophysiology underlying the cognitive dysfunction associated with SI, and few studies have examined the early cellular responses and neurobiological underpinnings. We induced SI in adult male Sprague-Dawley rats using an infusion of endothelin-1 in the CA1 dorsal hippocampus. Twenty-four hours later, we assessed cognition using the hippocampal-dependent object place recognition task. We also examined whether the resulting cognitive effects were associated with common markers of ischemia, specifically cell and synapse loss, gliosis, and inflammation, using histology and immunohistochemistry. Hippocampal SI led to subtle cognitive impairment on the object place recognition task 24 -hs post-injury. This was characterized by a significant difference in exploration proportion relative to a pre-injury baseline and a positive association between time spent with both the moved and unmoved objects. SI did not result in any detectable cell or synaptophysin loss, but did increase apoptosis, gliosis and inflammation in the CA1. Principal component analysis indicated the main variables associated with hippocampal SI included increased time spent with the unmoved object, gliosis, apoptosis and inflammation as well as decreased exploration proportion and CA1 cells. Our data demonstrate that hippocampal SI can lead to cognitive dysfunction 24 -hs after injury. Further, this appears to be driven by early degenerative processes including apoptosis, gliosis and inflammation, suggesting that these may be targets for early interventions treating hippocampal SI and its cognitive consequences.

Cardiovascular outcomes associated with Ultrathin bioresorbable polymer sirolimus eluting stents versus thin, durable polymer everolimus eluting stents following percutaneous coronary intervention in patients with type 2 diabetes mellitus: A meta-analysis of published studies.

Background:Percutaneous coronary intervention with the new generation drug eluting stents (DES) is 1 among the revascularization procedures required to treat patients with coronary artery disease (CAD). Since late stent thrombosis and silent myocardial infarction are highly associated with type 2 diabetes mellitus (T2DM), an analysis comparing the newer generation DES in this specific subgroup of patients would be scientifically relevant.In this analysis, we aimed to systematically compare the cardiovascular outcomes observed with the ultrathin bioresorbable polymer sirolimus eluting stents (SES) versus thin, durable polymer everolimus eluting stents (EES) following percutaneous coronary intervention in patients with T2DM.Methods:Through online databases, relevant studies comparing ultrathin bioresorbable polymer SES versus the durable polymer EES were carefully searched. The cardiovascular outcomes were assessed during a follow-up time period of 1 year and more than 1 year (1–5 years) respectively. This meta-analysis was carried out by the latest version of the RevMan software. Following analysis, the results were represented by odds ratios (OR) with 95% confidence intervals (CI).Results:A total number of 1967 patients with T2DM were included in this analysis. During a 1 year follow-up time period, target lesion failure (TLF) (OR: 0.59, 95% CI: 0.34–1.02; P = .06, target vessel revascularization (TVR) (OR: 0.97, 95% CI: 0.55–1.70; P = .91) and target lesion revascularization (TLR) (OR: 0.91, 95% CI: 0.44–1.87; P = .79) were similarly observed with ultrathin bioresorbable polymer SES versus the thin, durable polymer EES in these patients with T2DM. Other cardiovascular outcomes including myocardial infarction (MI), major adverse cardiac events, all-cause mortality (OR: 0.72, 95% CI: 0.37–1.40; P = .34), cardiac death and stent thrombosis (OR: 0.85, 95% CI: 0.45–1.62; P = .63) were also similarly observed with these 2 types of new stents. During a follow-up time period above 1 year (1–5 years), still no significant difference was observed in TLF, TVR, TLR, major adverse cardiac events, MI, all-cause mortality, cardiac death and stent thrombosis (OR: 0.62, 95% CI: 0.33–1.16; P = .14).Conclusions:The ultrathin bioresorbable polymer SES were similar to the durable polymer EES in these patients with T2DM. These 2 types of new generation stents were comparable in terms of cardiovascular outcomes. Hence, they might be recommended in patients with T2DM. Upcoming trials should be able to confirm this hypothesis.

Treatment of Delayed Cerebral Ischemia in Good-Grade Subarachnoid Hemorrhage: Any Role for Invasive Neuromonitoring?

BackgroundGood-grade aneurysmal subarachnoid hemorrhage (Hunt and Hess 1–2) is generally associated with a favorable prognosis. Nonetheless, patients may still experience secondary deterioration due to delayed cerebral ischemia (DCI), contributing to poor outcome. In those patients, neurological assessment is challenging and invasive neuromonitoring (INM) may help guide DCI treatment.MethodsAn observational analysis of 135 good-grade SAH patients referred to a single tertiary care center between 2010 and 2018 was performed. In total, 54 good-grade SAH patients with secondary deterioration evading further neurological assessment, were prospectively enrolled for this analysis. The cohort was separated into two groups: before and after introduction of INM in 2014 (pre-INMSecD: n = 28; post-INMSecD: n = 26). INM included either parenchymal oxygen saturation measurement (ptiO2), cerebral microdialysis or both. Episodes of DCI (ptiO2 < 10 mmHg or lactate/pyruvate > 40) were treated via induced hypertension or in refractory cases by endovascular means. The primary outcome was defined as the extended Glasgow outcome scale after 12 months. In addition, we recorded the amount of imaging studies performed and the occurrence of silent and overall DCI-related infarction.ResultsSecondary deterioration, impeding neurological assessment, occurred in 54 (40.0%) of all good-grade SAH patients. In those patients, a comparable rate of favorable outcome at 12 months was observed before and after the introduction of INM (pre-INMSecD 14 (50.0%) vs. post-INMSecD 16, (61.6%); p = 0.253). A significant increase in good recovery (pre-INMSecD 6 (50.0%) vs. post-INMSecD 14, (61.6%); p = 0.014) was observed alongside a reduction in the incidence of silent infarctions (pre-INMSecD 8 (28.6%) vs. post-INMSecD 2 (7.7%); p = 0.048) and of overall DCI-related infarction (pre-INMSecD 12 (42.8%) vs. post-INMSecD 4 (23.1%); p = 0.027). The number of CT investigations performed during the DCI time frame decreased from 9.8 ± 5.2 scans in the pre-INMSecD group to 6.1 ± 4.0 (p = 0.003) in the post-INMSecD group.ConclusionsA considerable number of patients with good-grade SAH experiences secondary deterioration rendering them neurologically not assessable. In our cohort, the introduction of INM to guide DCI treatment in patients with secondary deterioration increased the rate of good recovery after 12 months. Additionally, a significant reduction of CT scans and infarction load was recorded, which may have an underestimated impact on quality of life and more subtle neuropsychological deficits common after SAH.

Abstract 13196: The Utility of Silent Myocardial Infarction on Electrocardiogram as an ASCVD Risk Enhancer for Primary Prevention: The Multi-Ethnic Study of Atherosclerosis

Introduction: The 2018 AHA/ACC cholesterol guidelines introduced a new list of markers called “risk enhancers” that, if present, confer an increased risk of atherosclerotic cardiovascular disease (ASCVD). Notably absent is silent myocardial infarction (SMI) on electrocardiogram (ECG), even though SMI has been shown to be associated with future ASCVD. Hypothesis: Adding SMI to the pooled cohort equation (PCE) will improve risk discrimination and classification in those with intermediate ASCVD risk (5 - 20% 10-year risk). Methods: SMI was defined as a major Q-wave abnormality or minor Q/QS waves in the setting of major ST-T abnormalities in the absence of history of clinical cardiovascular disease. Incident ASCVD events included myocardial infarction, coronary heart disease death, and fatal and non-fatal stroke. Results: Among 2,278 intermediate-risk MESA participants, 48 (2.1%) had SMI at baseline. Over 32,150 person-years (median 15.8), incident ASCVD events occurred in 297/2,230 (13%) of those without SMI and 13/48 (27%) of those with SMI. In a Cox proportional hazards model that was adjusted for calculated 10-year ASCVD risk based on the PCE, SMI was associated with increased risk of ASCVD (HR 2.22, 95% CI 1.27 - 3.87, p = 0.005). Adding SMI to the PCE did not improve discrimination, with areas under the receiver operating characteristic curves for models without and with SMI of 0.5812 and 0.5874, respectively (p-value for difference 0.22; Figure 1a). The net reclassification improvement for adding SMI as a risk enhancer to reclassify participants from intermediate-risk to high-risk was 0.0242 (95% CI 0.0011 - 0.0472, p = 0.04; Figure 1b). Conclusions: Our findings suggest that the prevalence of SMI is 2.1% among those without known clinical cardiovascular disease considered intermediate-risk by the pooled cohort equation. In our analysis, SMI only modestly improved classification of risk, suggesting that it may not be very useful as an ASCVD risk enhancer.

Oxygen Gradient Ektacytometry-Derived Biomarkers Are Associated with the Occurrence of Cerebral Infarction, Acute Chest Syndrome and Vaso-Occlusive Crisis in Sickle Cell Disease

Background: In sickle cell disease (SCD), hemoglobin S (HbS) polymerizes upon deoxygenation, reducing red blood cell (RBC) deformability. RBC deformability can be measured over a gradient of oxygen tensions (pO2) with the Laser Optical Rotational Red Cell Analyzer (Lorrca) ektacytometer (RR Mechatronics). Oxygen gradient ektacytometry generates 3 key parameters: 1) EImax, RBC deformability at normoxia; 2) EImin, minimum RBC deformability upon deoxygenation; and 3) the point of sickling (PoS): the oxygen tension at which a 5% decrease in deformability is observed during deoxygenation, reflecting the patient-specific pO2 at which sickling begins (Figure 1A). Previously we showed that oxygen gradient ektacytometry-derived biomarkers correlate with measures of SCD disease severity and hemolytic rate (Rab et al. Blood 2018), and is associated with vaso-occlusive crisis (VOC) frequency (Rab et al, Blood 2019). In this study, we confirm these observations in 2 independent cohorts and extend it to occurrence of acute chest syndrome (ACS), stroke including silent cerebral infarction (SCI), and transcranial Doppler (TCD) outcome. Methods: We analyzed 2 cohorts of SCD patients; an adult patient cohort of 53 SCD patients, enrolled at either University Medical Center Utrecht, The Netherlands (UMCU, n=25) or Hospital Lyon France (LIBM, n=28), and a pediatric patient cohort of 190 SCD patients enrolled at Texas Children's Hospital, USA (TCH). Subjects were HbSS or HbS/β-thalassemia, with a substantial number of subjects on hydroxyurea (HU) therapy (adult cohort 66% and pediatric cohort 86%), and not on chronic transfusion therapy. Correlations between oxygen gradient ektacytometry-derived biomarkers and the clinical complications of stroke or silent infarcts (SCI), ACS, VOC were assessed in both pediatric and adult patients. Patient groups generally did not significantly differ significantly by age, gender or HU treatment in the adult cohort except for age, which was lower in the ACS+ group (25.3years (y) compared to 32.0y) and also lower in the VOC+ group (27.1y compared to 35.8y). In the pediatric cohort, patient groups differed significantly in the ACS+ group compared to the ACS- group by age (ACS- group 8.37, ACS+ group 10.9y) and HU treatment (ACS- group 76%, ACS+ group 93%). Similarly, age was significantly higher in the Stroke+ group compared to the Stroke- group (14.0y compared to 9.3y), which was also found when studying VOC (VOC+ group 11.6y, VOC- group 8.2y). Results: In the pediatric cohort, PoS was significantly higher in patients with ACS (mean 40.3 compared to 34.9 mmHg, p=0.0001, Figure 1B). In the adult cohort, PoS was also higher in those with ACS although this did not reach significance (p=0.053, Figure 1C). In the pediatric cohort, PoS was higher in patients with stroke or SI (mean 43.0 mmHg compared to mean 37.3 mmHg, p&amp;lt;0.05), Figure 1D). This finding was replicated in the adult cohort (p&amp;lt;0.05, Figure 1E). EImin and EImax in both cohorts were significantly lower in patients who experienced stroke or SCI (all p&amp;lt;0.05). PoS was higher and EImin and EImax lower in subjects with elevated TCD measurements (all p&amp;lt;0.01, Figure 1F and G). In the adult and pediatric patient cohort, PoS was higher in patients with recent VOC (both p&amp;lt;0.05, Figure 1H and I). Differences in mean PoS between pediatric and adult patient cohorts could be due to differences in treatment, age, genetic background or technical differences between Lorrca devices. Lower significance levels found in the adult patient cohort could be due to smaller sample size. Conclusion: We show that oxygen gradient ektacytometry provides functional, clinically relevant next generation biomarkers that are associated with ACS, stroke and VOC. This study therefore further validates the clinical usefulness of these biomarkers, in particular in relation to cerebral vasculopathy. Since our results merely describe an association and not causality further validation is warranted to establish how well oxygen gradient ektacytometry can assess disease severity. However, its parameters could already provide the clinician with information about patient RBC characteristics and sickling propensity that could aid in clinical decision making. Our results provide a rationale for further development of these biomarkers in the evaluation of novel therapies as part of clinical care, or clinical trial endpoints. Disclosures Rab: RR Mechatronics: Research Funding. Bos:RR Mechatronics: Research Funding. Cnossen:Takeda: Research Funding; Shire: Research Funding; Baxter: Research Funding; Bayer: Research Funding; Sobi: Research Funding; CSL behring: Research Funding; Nordic Pharma: Research Funding; Novo Nordisk: Research Funding; Pfizer: Research Funding. Wijk:Agios Pharmaceuticals Inc.: Research Funding; RR mechatronics: Research Funding. Sheehan:Emmaus: Research Funding; Global Blood Therapeutics: Research Funding; Novartis: Research Funding. van Beers:Pfizer: Research Funding; RR mechatronics: Research Funding; Agios: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding.

The T117S Variant of Cytochrome b5 Reductase 3 Increases the Risk for Ischemic Stroke with Enhanced Anemia in Mice with Sickle Cell Disease

Introduction. Stroke and silent infarcts are serious complications of sickle cell disease (SCD), occurring frequently in children between 3 and 14 years old. A vast amount of clinical and experimental evidence has concluded that decreased nitric oxide (NO) bioavailability and/or NO responsiveness, as is seen in SCD, is a major contributing factor in the pathogenesis of neurovascular disease. NO responsiveness, which occurs via NO-induced activation of soluble guanylate cyclase (sGC), requires reduced heme iron (Fe2+) in the sGC active site. We recently identified cytochrome b5 reductase 3 (Cyb5R3) as an sGC heme iron reductase in vascular smooth muscle (VSM), where it reverses the oxidized heme iron of sGC (Fe3+ --&amp;gt; Fe2+) to preserve NO sensing/signaling under conditions of oxidative stress. In a mouse model of SCD we have shown that knockdown of Cyb5R3 in VSM accelerates the development of pulmonary hypertension and cardiac remodeling. A missense variant of Cyb5R3 (T117S) that results in loss-of-function methemoglobin reductase activity occurs at a high frequency in persons of African ancestry (0.23 minor allele frequency). Unpublished baseline data from the Walk-PHaSSt trial (NCT00492531) reveals that persons with SCD who carry the T117S variant are at increased risk of ischemic stroke; these individuals self-reported almost 50% more (74 vs 51 cases per 1000 individuals) ischemic stroke than those with wild-type (WT) Cyb5R3. Hypothesis. We hypothesized that impaired reductase function of Cyb5R3 T117S leads to sustained sGC heme oxidation, which drives cerebral vascular dysfunction and exacerbates brain damage after ischemic stroke in SCD. Methods. Bone marrow transplant was used to create SCD mice with global expression of WT or T117S Cyb5R3, hereafter referred to as SS/WT or SS/T117S, respectively. All mice were male, C57Bl/6 background, and &amp;gt;85% engrafted with SS Hb for 12 weeks. Ischemic stroke was induced using transient middle cerebral artery occlusion (MCAO: 55 min occlusion, 48 hr reperfusion), after which brains were stained with 2,3,5-triphenyltetrazolium chloride (TTC,1%) to determine infarct volume. Blood was sampled before and after MCAO to assess effects of brain infarct on hematological parameters. Student's t-test was used for analysis of 2 groups and Pearson's R used for correlation analyses of brain infarct volume with hematology changes [(post-pre/pre) * 100]. Results. Global expression of T117S Cyb5R3 in SCD caused increased cerebral infarct volume (62.9 vs 26.7 cm3, P=0.003) and mortality (3/6 vs 0/6) relative to WT Cyb5R3. WT and T117S Cyb5R3 mice with SCD were similar in that both showed declining red blood cells (RBC), hemoglobin (Hgb) and hematocrit (Hct) as infarct volumes increased. In the SS/T117S group, the anemia was more severe in keeping with larger infarct volumes. There were different signatures to the hematologic changes that occurred with cerebral infarct in SCD. When compared to WT Cyb5R3, T117S caused the erythroid compartment to contract (RBC: -12.97% vs 13.41%, P=0.01; Hct: -19.75% vs 0.31%, P=0.025; Hgb: -17.93% vs 2.78%, P=0.017). In SS/WT mice platelet numbers increased more relative to SS/T117S (17.5 vs 9.7 * 103 cells/uL); and MPV, a measure of platelet activation, inversely correlated with brain infarct volume (r = -0.94, P=0.006), the opposite of what was seen in SS/T117S (r = 0.87, P=0.056). Monocytes seem to play an important role in the volume of brain infarct in SS/T117S as their numbers increased in parallel with infarct volume (r = 0.73, P=0.16), but followed the opposite trajectory in SS/WT mice (r = -0.75, P=0.14). Conclusion. These results indicate that Cyb5R3 is an important modifying factor in the evolution and outcome of ischemic brain injury in SCD. Our findings also raise questions on just how cerebral infarct modifies the anemia of SCD, as well as the role played by Cyb5R3 in the dynamics of that relationship. To what extent is the sGC-cGMP-PKG pathway involved at the cerebrovascular and erythropoietic levels? Does Cyb5R3 contribute resilience to ischemic stroke in SCD? The development and application of targeted therapies for effectively preventing and treating cerebrovascular disease in SCD rely on finding the answers to these questions. Disclosures No relevant conflicts of interest to declare.

Diabetic cardiovascular autonomic neuropathy in children

Abstract Diabetic cardiovascular autonomic neuropathy (CAN) encompasses damage to the autonomic nerve fibers innervating the heart and blood vessels, resulting in abnormalities in heart rate control and vascular dynamics. Clinical symptoms associated with CAN include resting tachycardia, postural hypotension, dizziness, syncope, exercise intolerance, silent myocardial infarction. The earliest finding of CAN, even at the subclinical stage, is a decrease in heart rate variability (HRV) Purpose To study CAN prevalence and understand the diagnostic capabilities of HRV - tests of diabetic cardiovascular autonomic neuropathy in children with type 1 diabetes. Methods 100 children with type 1 diabetes were assessed for CAN (age 15.2 yrs [9.0–17.8], duration 6.5 yrs [4.0–10.6], HbA1c 8.1% 6.3–9.7]). The degree of compensation of diabetes was estimated according to criteria ISPAD Consensus Guidelines, 2018. Optimal level (HbA1c &amp;lt;7.0%) of compensation was revealed in 62% of children (group I) and nonoptimal in 38% of children (group II). For evaluation of the CAN we used HRV - tests: RR 30:15 ratio, ΔRR quiet breath, ΔRR deep breath, BP response to standing. Results Diabetic cardiovascular autonomic neuropathy was diagnosed in 41 children: in group I – in 6 (29%) and in group II – 35 (71%) children (p=0.00001). The prevalence of DCN correlated with HbA1c level in children and adolescents (groups I and II): ΔRR quiet breath r=−0.47 &amp; r=−0.9; ΔRR deep breath r=−0.65 &amp; r=−0.85; RR30:15 r=−0.77 &amp; r=−0.88 respectively. Prevalence of CAN increased parallel to type 1 diabetes duration (p&amp;lt;0.01). Conclusions Diabetic cardiovascular autonomic neuropathy in children with type 1 diabetes was diagnosed in 41%. Prevalence of diabetic cardiovascular autonomic neuropathy increases parallel to type 1 diabetes duration (p&amp;lt;0.01). In this study we found an association between HRV indexes and HbA1c level. This provides support for HRV - testing to assess diabetic cardiovascular autonomic neuropathy in children. Funding Acknowledgement Type of funding source: None

Silent myocardial infarction among young sudden cardiac death victims

Abstract Background Silent myocardial infarctions (SMIs) occur with atypical or no symptoms at all. The burden of SMIs among sudden cardiac death victims have recently been acknowledged. However, the prevalence of previously undetected SMI in young victims remains unclear. Purpose The aim of the present study was to determine the prevalence of autopsy verified SMI in SCD victims under 50 years old without a prior diagnosis of coronary artery disease (CAD). Methods Fingesture study consists of systematically collected consecutive victims of SCD in Northern Finland between years 1998–2017 (n=5,869). According to Finnish law, all unexpected deaths undergo medico-legal autopsy. The autopsies routinely included histological examinations, and a toxicology investigation was carried out if needed. The SMI was defined as focal scar detected by macroscopic evaluation of the dissected ventricles and histologic analysis of the myocardial samples with an absence of a history of previously diagnosed CAD. Pre-mortem clinical history was obtained from medical records, standardized questionnaire to the closest family members of the victims and police reports about the conditions of the death. Results Overall, 10.4% off all SCDs occurred among victims under the age of 50 years (610 victims). Most common underlying cause of SCD among young was CAD (44%). About 90% of the victims had no clinical diagnosis of CAD, however, 34% (78 victims) had previously undetected myocardial scar at autopsy indicating a previous SMI. The mean age of the young SMI victims was 44±4 and they were mostly men (87%). 24% of SCDs occurred during physical activity and 21% had SCD outdoors. The mean heart weight was 466±110 g and 67% had hypertrophied hearts. Three vessel disease was detected in 69% of the victims. Alcohol was detected in 17% of victims in toxicology investigations. Conclusions Previously undetected myocardial infarction is also common among young victims who experienced CAD associated SCD. Three vessel disease and cardiac hypertrophy were common autopsy findings among young SMI victims and about a fourth had SCD during physical activity. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Sigrid Juselius Foundation, Finnish Foundation for Cardiovascular Research

Non-cardiovascular comorbidities in patients with chronic coronary syndromes (review) (2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes)

С areful evaluation of patient history, including of anginal symptoms, and evaluation of risk factors and manifestation of coronary artery disease (CAD), as well as proper physical examination and basic testing, are crucial for the diagnosis and management of chronic coronary syndrome(s) (CCS) and non-cardiovascular comorbidities. Anti-ischaemic treatment must be adapted to the individual patient based on comorbidites, co-administered therapies, expected tolerance and adherence, and patient preferences. The choice of anti-ischaemic drugs to treat chronic coronary sydromes should be adapted to the patient’s heart rate, blood pressure, and left-ventricular (LV) function. In patients with active cancer treatment decisions should based on life be expectancy, additional comorbidities such as thrombocytopenia, increased thrombosis propensity. and potential interactions between drugs used in CCS management and antineoplastic agents. In asymptomatic patients with diabetes mellitus, a periodic resting electrocardiogram is recommended for cardiovascular detection of conduction abnormalities, atrial fibrillation, and silent myocardial infarction. Recommendations for chronic kidney disease (CRD): use iodinated contrast agents is minimized in patients with severe CKD and preserved urine production to prevent further deterioration. It is recommended that particular attention is paid to side effects of drugs, intolerance, and overdosing in elderly patients with chronic coronary syndromes. Hormone replacement therapy is not recommended for risk reduction in post- menopausal women. Тransmyocardial revascularization is not recommended in patients with debilitating angina refractory to optimal medical and revascularization strategies.

Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) study: what have we learned from it?

The Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) study is the largest natural history study on patients with 50–99% asymptomatic carotid stenosis (ACS). It included 1,121 ACS individuals with a follow-up between 6 and 96 months (mean: 48 months). During the last 15 years, several important ACSRS substudies have been published that have contributed significantly to the optimal management of ACS patients. These studies have demonstrated that specific baseline clinical characteristics and ultrasonic plaque features after image normalization (namely carotid plaque type, gray scale median, carotid plaque area, juxtaluminal black area without a visible echogenic cup, discrete white areas in an echolucent part of a plaque, silent embolic infarcts on brain computed tomography scans, a history of contralateral transient ischemic attacks/strokes) can independently predict future ipsilateral cerebrovascular events. The ACSRS study provided proof that by use of a computer program to normalize plaque images and extract plaque texture features, a combination of features can stratify patients into various categories depending on their stroke risk. The present review will discuss the various reported predictors of future ipsilateral cerebrovascular events and how these characteristics can be used to calculate individual stroke risk.

Diabetic autonomic neuropathies as a major risk factor for silent myocardial ischemia and infarction: a literature review

A substantial number of myocardial infarctions (MIs) are asymptomatic or associated with mi-nor and atypical symptoms. These symptoms are often atypical or even absent, especially in di-abetic patients. A number of studies on this topic have shown that in the presence of myocardial ischemia and infarction, diabetic patients report angina less frequently than non-diabetic pa-tients. In this article review, we researched several published articles written about this subject and investigated the relationship between Diabetes Mellitus (DM) in patients and the occur-rence of silent myocardial ischemia and infarction due to the onset of diabetic neuropathy (DN), which is brought about by prolonged diabetes. Based on our research of published articles and studies, we found overwhelming evidence that supports the fact that diabetic autonomic neu-ropathy (DAN) is a major contributing factor in the morbidity of silent myocardial ischemia and infarction among patients suffering from DM. Â

Blood Neutrophil/Lymphocyte Ratio Is Associated With Cerebral Large-Artery Atherosclerosis but Not With Cerebral Small-Vessel Disease

Background and Objective: The blood neutrophil/lymphocyte ratio (NLR) is a marker of peripheral inflammation, with a high NLR associated with an increased risk of cardiovascular events and poor prognosis in ischemic stroke. However, few data are available on the differential impact of the blood NLR on different silent cerebral vascular pathologies, including cerebral large-artery atherosclerosis (LAA) and cerebral small-vessel disease (CSVD), in neurologically healthy individuals.Methods: We evaluated cardiovascular risk factors, brain magnetic resonance imaging (MRI), and MR angiography of 950 individuals without any neurological diseases. The study participants were divided into three groups according to NLR tertile (low, middle, and high). The presences of extracranial (EC) and intracranial (IC) atherosclerosis were considered to indicate LAA on brain MR angiography. The presences of silent lacunar infarction (SLI) and cerebral white matter hyperintensities (WMHs) were analyzed as indices of CSVD on brain MRI.Results: In univariate analysis, the high NLR tertile group showed a high prevalence of old age, hyperlipidemia, and renal dysfunction and higher fasting glucose. Multivariable logistic regression analysis revealed that indices of LAA (EC atherosclerosis [odds ratio: 1.88; 95% confidence interval: 1.14–3.09; p = 0.01] and IC atherosclerosis [odds ratio: 1.87; 95% confidence interval: 1.15–3.06; p = 0.01]) were more prevalent in the highest NLR tertile group than in the lowest NLR tertile group after adjustment for cardiovascular risk factors. However, no significant differences were found in the prevalence of CSVD indices (SLI and WMHs) among the three NLR tertile groups.Conclusions: A high NLR is associated with the development of cerebral LAA but not CSVD.

Recent silent infarcts do not increase the risk of haemorrhage after intravenous thrombolysis

Haemorrhagic transformation (HT) is one of the main risks of intravenous thrombolysis (IVT) for acute ischaemic stroke. Contraindications serve to exclude patients at high risk of HT after IVT. One of these contraindications is a stroke within the preceding 3months. It is unclear if this contraindication should include recent clinically silent infarcts (RSIs). The aim of this study was to investigate whether RSIs are associated with a higher risk of HT and a worse clinical outcome after IVT for acute ischaemic stroke. In a retrospective monocentric cohort study, all patients who received IVT for acute ischaemic stroke based on magnetic resonance imaging were assessed over 5years. RSIs were defined as lesions with diffusion restriction and positive signal on fluid attenuated inversion recovery sequences. Patients with RSIs (RSI+) were compared to patients without RSIs (RSI-) regarding HT after IVT and clinical outcome. In all, 981 patients who had received IVT for acute ischaemic stroke demonstrated by magnetic resonance imaging were identified. RSIs were detected in 115 patients (11.5%). HT after IVT was observed in 32 (28.3%) RSI+ and 56 (25.8%) RSI- patients (P=0.624). Symptomatic intracerebral haemorrhage was noted in two (1.8%) RSI+ and five (2.3%) RSI- patients (P=1.000). No differences in clinical outcome were observed. The detection of RSIs in patients treated with IVT for acute ischaemic stroke was not associated with a higher risk of HT or a worse clinical outcome. The results of this study argue against considering RSIs as a contraindication for IVT.

Noninvasive model for predicting future ischemic strokes in patients with silent lacunar infarction using radiomics

BackgroundThis study aimed to investigate integrating radiomics with clinical factors in cranial computed tomography (CT) to predict ischemic strokes in patients with silent lacunar infarction (SLI).MethodsRadiomic features were extracted from baseline cranial CT images of patients with SLI. A least absolute shrinkage and selection operator (LASSO)–Cox regression analysis was used to select significant prognostic factors based on ModelC with clinical factors, ModelR with radiomic features, and ModelCR with both factors. The Kaplan–Meier method was used to compare stroke-free survival probabilities. A nomogram and a calibration curve were used for further evaluation.ResultsRadiomic signature (p < 0.01), age (p = 0.09), dyslipidemia (p = 0.03), and multiple infarctions (p = 0.02) were independently associated with future ischemic strokes. ModelCR had the best accuracy with 6-, 12-, and 18-month areas under the curve of 0.84, 0.81, and 0.79 for the training cohort and 0.79, 0.88, and 0.75 for the validation cohort, respectively. Patients with a ModelCR score < 0.17 had higher probabilities of stroke-free survival. The prognostic nomogram and calibration curves of the training and validation cohorts showed acceptable discrimination and calibration capabilities (concordance index [95% confidence interval]: 0.7864 [0.70–0.86]; 0.7140 [0.59–0.83], respectively).ConclusionsRadiomic analysis based on baseline CT images may provide a novel approach for predicting future ischemic strokes in patients with SLI. Older patients and those with dyslipidemia or multiple infarctions are at higher risk for ischemic stroke and require close monitoring and intensive intervention.

PM Association Between Silent Lacunar Infarcts And Muscle Strength: The Bunkyo Health Study

Silent lacunar infarcts by definition, lack clinically overt stroke-like symptom, are occasionally found by brain magnetic resonance imaging (MRI) scan in asymptomatic elderly individuals. A previous study revealed that more than 25% of elderly people have silent lacunar infarcts. The main risk factors for lacunar infarcts and stroke were reported as aging, hypertension, and smoking. While a recent study showed that low muscle strength is also a risk factor for cerebrovascular events, it remains unclear whether low muscle strength is a risk factor for silent lacunar infarcts. PURPOSE: To investigate the association between muscle strength and silent lacunar infarcts in the elderly people living in urban community. METHODS: This study included 1,536 elderly people without past history of cerebral vascular events, aged 65-84 years living in an urban area of Tokyo, Japan (Bunkyo Health Study). All participants underwent brain MRI scan and silent lacunar infarcts were defined as the presence of 1 or more lacunar infarcts. Isokinetic muscle strength of knee extensors was evaluated at angular velocity of 60 degree per seconds using dynamometer. Subjects was categorized tertiles (high, medium, and low) by muscle strength, and compared the prevalence of silent lacunar infarcts. RESULTS: Mean age of subjects was 73.0±5.4 years old and 58.9% were female. Two hundred fifty-two (16.4%) subjects were diagnosed as silent lacunar infarcts, and the subjects categorized as lower muscle strength showed higher prevalence of silent lacunar infarcts (high: 12.3%, medium: 17.7%, and low: 19.3%, p for trend 0.003), while skeletal muscle indices among the groups were similar. After multivariate adjustment by age, sex, body mass index, smoking status, physical activity, hypertension, diabetes, and dyslipidemia, the trend was still significant and the odds ratio for having silent lacunar infarcts was significantly higher in the lowest muscle strength tertile compared to the highest tertile [(High: 1.00 (reference), medium: 1.42 (95%CI: 0.98-2.04), Low: 1.48 (1.02-2.14), p for trend 0.043]. CONCLUSIONS: In the elderly people living in urban community, lower muscle strength of knee extensors was associated with higher prevalence of silent lacunar infarcts independent of other established risk factors.

Reduced muscle strength of knee extensors is a risk factor for silent lacunar infarcts among Japanese elderly people: the Bunkyo Health Study

AbstractBackgroundSilent lacunar infarcts (SLIs) are often incidentally diagnosed by brain magnetic resonance imaging in elderly people and are associated with the future onset of stroke, dementia, and frailty. While decreased muscle strength was reported as a risk factor for stroke, it is still unclear whether it also predisposes to SLI. In this study, we investigated the association between muscle strength and SLI in elderly subjects.MethodsThe subjects were 1536 elderly people aged 65–84 years without previous stroke events, living in an urban area of Tokyo, Japan, and recruited in the Bunkyo Health Study. Lacunar infarcts were defined by brain magnetic resonance imaging. Muscle strength of the knee extensors was measured using a dynamometer. After categorizing subjects by age and sex, we divided them into three groups based on muscle strength tertiles (High, Medium, and Low) and investigated the association between muscle strength and SLI.ResultsThe mean subject age was 73.0 ± 5.4 years, and 58.9% were female. The prevalence of SLI was 16.4% and was inversely associated with muscle strength (High, 12.3%; Medium, 17.7%; and Low, 19.3%; P for trend 0.003). After multivariate adjustment, the odds ratio for SLI was increased in the Medium and Low groups compared with the High group (High, 1.00 [reference]; Medium, 1.42 [95% confidence interval: 0.98–2.04]; and Low: 1.48 [1.02–2.14]), and the linear trend across the three groups was significant (P for trend 0.043).ConclusionsReduced knee extensor muscle strength is associated with SLI among Japanese elderly, independently of other established risk factors.