Left Atrial Appendage Closure Yields Favorable Cardio- and Cerebrovascular Outcomes in Patients With Non-valvular Atrial Fibrillation and Prior Stroke

Introduction: Patients with non-valvular atrial fibrillation (NVAF) and previous stroke are at significantly higher risk of stroke recurrence. Data on the efficacy of left atrial appendage closure (LAAC) on these patients is limited. The aim of this study was to investigate the differences of LAAC efficacy on long-term cardio- and cerebrovascular outcomes in NVAF patients with vs. without prior stroke.Methods: Three hundred and seventy consecutive NVAF patients who underwent LAAC were enrolled and divided into stroke and non-stroke groups based on history of previous stroke. Endpoints, such as thromboembolism, major bleeding, and mortality post-LAAC, were followed up among groups.Results: Patients in the stroke group had higher mean CHA2DS2-VASc and HAS-BLED scores compared to the non-stroke group (5.1 vs. 3.6 and 4.1 vs. 3.4, both P < 0.001, respectively). Over a median follow-up of 2.2 years, there were no significant differences in incidence rates of thromboembolism, device-related thrombus (DRT), major bleeding, and combined efficacy endpoints between the two groups. In both stroke and non-stroke groups, LAAC decreased the risk of thromboembolism [relative risk reduction (RRR) 87.5%, P = 0.034, and 74.6%, P = 0.004, respectively] and major bleeding (RRR 68.8%, P = 0.034, and 68.6%, P = 0.007, respectively) compared with predicted risk. The RRR in thromboembolism was greater in patients with vs. without prior stroke (OR 2.45, 95% CI: 1.20–5.12, P = 0.016). The incidence rates of all-cause mortality and non-cardiovascular death were similar between the two groups, but the risks of cardiovascular death post-LAAC both before (1.4% vs. 8.1%, respectively, P = 0.038) and after adjustment for confounding factors (P = 0.048) were significantly decreased in the stroke group.Conclusions: Patients with vs. without prior stroke did not exhibit a worse clinical prognosis after LAAC. LAAC may provide an increased benefit in cardio-cerebrovascular outcomes in patients with previous stroke compared to those without previous stroke. Further research is necessary to evaluate the efficacy of LAAC in this field.

Incidence and Risk Factors for Acute Transient Contrast‐Induced Neurologic Deficit: A Systematic Review With Meta‐Analysis

BACKGROUND After MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) demonstrated that endovascular therapy improved outcomes in patients with stroke, the number of endovascular procedures has risen sharply. We describe acute transient contrast‐induced neurological deficit (ATCIND), a group of neurological syndromes associated with arterial contrast administration during angiography. Our goal is to elucidate the incidence, risk factors, outcomes, pathogenesis, and diagnostic characteristics of ATCIND. Our primary objective is to elucidate the incidence of ATCIND in the setting of coronary or cerebral angiography. Secondary outcomes include potential risk factors, demographics, treatment modalities, and patient recovery. METHODS The data that support the findings of this study are available from the corresponding author on reasonable request. The databases of the Cochrane Library, MEDLINE, Web of Science, and Embase were queried, yielding studies from 1974 to 2021. Inclusion criteria for articles were the following: (1) contrast‐induced encephalopathy, contrast‐induced neurotoxicity, or cortical blindness after contrast administration during angiography were the focus of the article; (2) incidence was reported; (3) studies included ≥3 cases; and (4) follow‐up tests were described to rule out other causes. Exclusion criteria included the following: (1) incidence was not reported; (2) unavailable in the English language; (3) abstracts and unpublished studies; and (4) did not exclude other possible causes, or findings suggested other possible causes, such as worsening ischemic injury. Of 627 articles, 7 were retained. This systematic review with meta‐analysis was performed in accordance with guidelines provided by the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) and the Meta‐Analysis of Observational Studies in Epidemiology (MOOSE) checklists. Independent extraction by multiple reviewers was performed. Data were pooled using a random‐effects model. RESULTS The primary study outcome was incidence of ATCIND, which was formulated before data collection began. We hypothesized that the pooled incidence of ATCIND would be similar to that of individual studies. A total of 70 of 21007 patients had the diagnosis of contrast‐induced encephalopathy, contrast‐induced neurotoxicity or angiography‐associated cortical blindness, and ATCIND. The incidence rate of ATCIND is estimated to be 0.51% (CI, 0.3%–1.0%; P <0.001 [ I 2 =29.3]), or 51 per 10 000 patients. Pooled data for risk factors for contrast‐induced encephalopathy were higher contrast dose (odds ratio [OR], 1.072; 95% CI, 0.952–1.192 [ P <0.001]; I 2 =0), and prior stroke (OR, 5.153; CI 1.726–8.581 [ P =0.003]; I 2 =0). Contrast dose >150 mL was a positive, significant predictor of visual disturbance (OR, 7.083; CI, 1.1742–42.793 [ P =0.033]). Full recovery is estimated at 89.5% (95% CI, 76.9%–95.6%; P <0.001 [ I 2 =0]). CONCLUSIONS This study confirms the rare incidence of ATCIND, although it shows moderate heterogeneity, likely reflecting the type of angiography performed. Risk factors include larger contrast dose and prior stroke. Full recovery occurs in the majority of patients. It should remain in the differential diagnosis in patients with certain risk factors for blood–brain barrier compromise.

Novel Functional, Health, and Genetic Determinants of Cognitive Terminal Decline: Kuakini Honolulu Heart Program/Honolulu-Asia Aging Study

To investigate inter-individual differences in cognitive terminal decline and identify determinants including functional, health, and genetic risk and protective factors, data from the Honolulu Heart Program/Honolulu-Asia Aging Study, a prospective cohort study of Japanese American men, were analyzed. The sample was recruited in 1965-68 (ages 45-68 years). Longitudinal performance of cognitive abilities and mortality status were assessed from Exam 4 (1991-1994) through June 2014. Latent class analysis revealed two groups: maintainers retained relatively high levels of cognitive functioning until death and decliners demonstrated significant cognitive waning several years prior to death. Maintainers were more likely to have greater education, diagnosed coronary heart disease, and presence of the apolipoprotein E (APOE) ε2 allele and FOXO3 G allele (SNP rs2802292). Decliners were more likely to be older and have prior stroke, Parkinson’s disease, dementia, and greater depressive symptoms at Exam 4, and the APOE ε4 allele. Findings support terminal decline using distance to death as the basis for modeling change. Significant differences were observed between maintainers and decliners 15 years prior to death, a finding much earlier compared to the majority of previous investigations.

Combined Catheter Ablation and Left Atrial Appendage Closure in Atrial Fibrillation Patients with and without Prior Stroke

Background. Combined atrial fibrillation (AF) ablation and left atrial appendage closure (LAAC) has been practiced for management of both the symptoms and the high stroke risk of AF. Data of the combined procedure in selected patients with prior stroke are limited. The aim of this study is to compare the safety and efficacy of combined catheter ablation and LAAC between AF patients with and without prior stroke. Methods and Results. This retrospective study enrolled 296 patients who underwent combined procedures of AF ablation and LAAC. Patients were divided into two groups: 81 patients with prior stroke (Stroke group) and 215 patients without prior stroke (Control group). Combined procedures were successfully performed in all the patients. Patients in the Stroke group had higher CHA2DS2-VASc scores (4.9 ± 1.2 vs. 3.2 ± 1.0, P < 0.001 ) and higher HAS-BLED scores (3.5 ± 1.1 vs. 3.0 ± 1.0, P < 0.001 ) compared with those in the Control group. Procedure-related complications in the Stroke group included two pericardial effusions and two groin hematomas, which did not differ significantly fromthe Control group (4.9% vs. 4.2%, P = 0.778 ). After a mean follow-up of 20 months, the AF-free rate of the Stroke group was comparable with that of the Control group (64.2% vs. 68.4%, P = 0.495 ). The relative risk reductions in stroke and bleeding (observed rate compared to that predicted from the CHA2DS2-VASc and HAS-BLED scores) were 80% and 79%, respectively, in the Stroke group, and 62% and 62%, respectively, in the Control group. Conclusions. The combination of catheter ablation and LAAC is safe and efficient in selected AF patients with prior stroke. It was observed that patients with prior stroke may benefit more from risk reductions of stroke and bleeding following the combined procedure.

Clinical Characteristics of COVID-19 Infection

The typical clinical symptoms of the patients who suffered from the novel viral pneumonia were fever, cough, and myalgia or fatigue with abnormal chest CT, and the less common symptoms were sputum production, headache, hemoptysis, and diarrhea. This new infectious agent is more likely to affect older males to cause severe respiratory diseases. Major risk factors for severe illness and mortality from COVID-19 are age, comorbidities such as: heart disease, hypertension, prior stroke, diabetes, chronic lung disease, and chronic kidney disease and associated with adverse outcomes. Loss of taste and smell preceding the onset of respiratory symptoms has been reported.

Association of Left Atrial Sphericity with Risk of Stroke in Patients with Atrial Fibrillation. Sub-Analysis of the ASSAM Study

Purpose The study was designed to evaluate the value of left atrial (LA) sphericity (LASP) in the identification of patients with atrial fibrillation (AF) who had prior ischemic stroke. The secondary aim was to investigate the possibility of improving stroke risk assessment based on six geometrical variables of LA. Methods This prospective observational study involved 157 patients: 74 in the stroke group and 83 in the control. All patients had cardiac computed tomography (CT) performed to analyze LA volume and dimensions. LASP and the discriminant function of six geometrical measurements were calculated. Results Multivariate logistic regression analysis showed a significant association of stroke with and gender, diabetes, CHA2DS2-VASc score, LA anteroposterior diameter, and LA sphericity. Patients with prior stroke had lower LASP than those without (66.6 ± 10.3% vs. 70.5 ± 7%; p = 0.0062). The most accurate identification of patients with a history of ischemic stroke was achieved by using a function of six geometrical measurements, the sphericity and volume coefficient. The C-statistic was higher for the above discriminant function (0.7273) than for LASP (0.3974). The addition of the discriminant function to the CHA2DS2-VASc score increased the performance of the risk score alone. Conclusion LASP is associated with prior stroke in AF patients. The proposed new formula for identification of AF patients who are at risk of stroke, based on geometrical measurements of LA, is superior to the basic LASP in identification of AF patients with a history of stroke.

Does Prior Stroke Predict Long-Term Recurrent Stroke After Percutaneous Coronary Intervention? Five-Year Results From a Large Cohort Study

Background: We found a positive correlation between the prior stroke history and recurrent stroke in patients who underwent percutaneous coronary intervention (PCI) in our previous study, which indicated the close interaction of stroke and cardiovascular diseases. However, it is unclear whether prior stroke is still associated with worse prognosis at a longer follow-up period.Methods: A total of 10,724 coronary heart disease (CHD) patients who received PCI from January to December 2013 were prospectively enrolled and were subsequently divided into the prior stroke (n = 1,150) and non-prior stroke (n = 9,574) groups according to their history. Baseline characteristics and 5-year outcomes were recorded.Results: Patients with prior stroke had more clinical risk factors, as well as more extensive coronary artery lesions. Although in-hospital outcomes were similar between patients from the two groups, the 5-year follow-up result revealed that patients with prior stroke experienced higher incidence of stroke, major adverse cardiac and cerebrovascular events (MACCEs), all-cause death, and cardiac death (7.0 vs. 3.0%, p &lt; 0.001; 25.9 vs. 20.3%, p &lt; 0.001; 5.3 vs. 3.5%, p = 0.002; 3.1 vs. 2.1%, p = 0.032, respectively). After the propensity score matching, the 5-year stroke rate was still higher in the prior stroke group (6.8 vs. 3.4%, p = 0.001). The multivariable regression analysis also identified the prior stroke as a risk predictor of the 5-year stroke (HR = 2.011, 95% CI: 1.322–3.059, p = 0.001).Conclusions: Coronary heart disease patients with prior stroke who received PCI had a higher incidence of 5-year long-term adverse cardiovascular and cerebrovascular events, especially recurrent stroke. Prior stroke was a strong risk predictor of future stroke events.

Abstract 1122‐000237: Prior Vascular Risk Factors Affecting Presentation Time and Utilization of Acute Ischemic Stroke Therapies

Introduction : Multiple factors have been reported to influence the time between onset of symptoms in acute ischemic stroke and hospital presentation. Although education level is one independent factor in presentation, as we previously reported, health literacy has not been fully assessed regarding specific patient knowledge on stroke or its known risk factors. This study aims to determine whether having a history of vascular risk factors such as prior stroke, coronary artery disease (CAD), or atrial fibrillation (AF) influence presentation time and acute ischemic stroke therapy utilization. Methods : This study included 250 acute ischemic stroke patients presenting to a large academic community hospital from February to December 2018. Educational level was defined within four categories: Grade School, High School, College or Higher, and Unknown. Last seen normal, symptom onset, and arrival times were acquired. Vascular risk factors chosen for this study included prior stroke, CAD, and AF. History of vascular risk factors was verified by medical documentation showing prior diagnosis by physician. Initial NIH Stroke Scale score, stroke location, vessel involved, LDL, hemoglobin A1c, gender, and race were also obtained. Patients were categorized based on their level of education, the presence or absence of vascular risk factors, and utilization of tPA or thrombectomy (MT). The primary outcomes were onset‐to‐arrival time (OTA), in minutes, and utilization rates of acute ischemic stroke therapies (either tPA, MT, or both). Subgroup analysis was conducted to associate education level with each vascular risk factor, comparing OTA and acute ischemic stroke therapy utilization rate. Results : As previously reported, educational level was inversely associated with OTA and positively associated with utilization of at least one acute ischemic stroke therapy. Prior stroke, CAD, and AF showed a substantial OTA decrease for all education groups except for College. Prior stroke decreased OTA in Grade School by 24% (764 vs. 579); High School by 30% (222 vs. 154) and College by 20% (52 vs. 41). CAD decreased OTA in Grade School by 65% (734 vs. 253), High School by 14% (209 vs. 180), and College by 3% (50 vs 49). AF decreased OTA in Grade School by 88% (764 vs. 91) and High School by 56% (216 vs. 95), but increased in College by 35% (47 vs. 64). History of prior stroke decreased utilization of both tPA and MT by 14%; CAD increased tPA use by 8% and MT by 5%; while AF increased tPA use by 9% and MT by 12%. Conclusions : Having at least one prior vascular risk factor (prior stroke, CAD, AF), diagnosed by a physician, was associated with lower OTA in Grade School and High School educated patients. A history of prior stroke was associated with lower acute stroke therapy utilization (tpa and MT), while both CAD and AF were associated with increased acute stroke therapy utilization.

Prior Stroke and Age Predict Acute Ischemic Stroke Among Hospitalized COVID-19 Patients: A Derivation and Validation Study

Objectives: Our objective was to identify characteristics associated with having an acute ischemic stroke (AIS) among hospitalized COVID-19 patients and the subset of these patients with a neurologic symptom.Materials and Methods: Our derivation cohort consisted of COVID-19 patients admitted to Yale-New Haven Health between January 3, 2020 and August 28, 2020 with and without AIS. We also studied a sub-cohort of hospitalized COVID-19 patients demonstrating a neurologic symptom with and without an AIS. Demographic, clinical, and laboratory results were compared between AIS and non-AIS patients in the full COVID-19 cohort and in the sub-cohort of COVID-19 patients with a neurologic symptom. Multivariable logistic regression models were built to predict ischemic stroke risk in these two COVID-19 cohorts. These 2 models were externally validated in COVID-19 patients hospitalized at a major health system in New York. We then compared the distribution of the resulting predictors in a non-COVID ischemic stroke control cohort.Results: A total of 1,827 patients were included in the derivation cohort (AIS N = 44; no AIS N = 1,783). Among all hospitalized COVID-19 patients, history of prior stroke and platelet count ≥ 200 × 1,000/μL at hospital presentation were independent predictors of AIS (derivation AUC 0.89, validation AUC 0.82), irrespective of COVID-19 severity. Among hospitalized COVID-19 patients with a neurologic symptom (N = 827), the risk of AIS was significantly higher among patients with a history of prior stroke and age &lt;60 (derivation AUC 0.83, validation AUC 0.81). Notably, in a non-COVID ischemic stroke control cohort (N = 168), AIS patients were significantly older and less likely to have had a prior stroke, demonstrating the uniqueness of AIS patients with COVID-19.Conclusions: Hospitalized COVID-19 patients who demonstrate a neurologic symptom and have either a history of prior stroke or are of younger age are at higher risk of ischemic stroke.

Risk prediction of major adverse cardiac events by high sensitivity troponin is modified by comorbidities

Background High-sensitivity cardiac troponin (hs-cTn) is a well-established biomarker for the evaluation of Emergency Department (ED) patients with possible acute coronary syndrome. These patients often have comorbid conditions that may impact hs-cTn values. However, prior studies and current guidelines addressing the relationship between comorbidities and hs-cTn are limited. Purpose To determine whether an interaction exists between comorbidities and baseline hsTnT values on the risk of 30-day major adverse cardiac events (MACE) in a multicenter United States (US) cohort. Methods Adult ED patients with suspected acute coronary syndrome were prospectively enrolled in a multicenter cohort study in the US. Baseline blood samples were collected and hs-cTnT concentrations were measured at a central laboratory. Comorbid conditions, such as obesity, hypertension, hyperlipidemia, diabetes, coronary artery disease, congestive heart failure, renal disease, peripheral vascular disease, prior stroke, and history of coronary interventions, were collected at time of enrollment. The primary outcome was adjudicated MACE, defined as occurrence of myocardial infarction, cardiovascular or uncertain death, or coronary revascularization within 30 days. Hs-cTnT values were dichotomized using manufacturer's limit of quantification (LOQ) at 6 ng/dL and the upper reference limit (URL) of 19 ng/dL. The utility the LOQ and URL cut-offs in predicting MACE was evaluated using logistic regression. Effect modification of comorbid conditions was independently evaluated by including an interaction term between comorbidity and hs-cTnT. Results Among 1460 participants with a baseline hs-cTn measurement, 46.3% (676/1460) were female and 37.1% (542/1460) were Black with a mean age of 57.6±12.9 years. The prevalence of MACE was 14.4% (210/1460). Participants with a baseline hs-cTnT below LOQ were 0.08 (95% CI: 0.04–0.16) times less likely to have MACE compared to those exceeding LOQ. Those with a baseline hs-cTnT exceeding URL were 9.5 (95% CI: 7.0–12.9) times more likely to have MACE. The presence of prior stroke significantly modified the association between baseline hs-cTnT below LOQ and risk of MACE (p=0.006). Among those with prior stroke (n=158), there was no significant association between baseline hs-cTnT below LOQ and risk of MACE (p=0.451). For the association between hs-cTnT above URL and MACE, significant negative interaction was detected by hypertension (p&lt;0.001), hyperlipidemia (p=0.002), coronary artery disease (p=0.002), percutaneous coronary intervention (p=0.001), and congestive heart failure (p=0.038) comorbidity. Conclusion In a diverse, multicenter, US cohort the association between baseline hs-cTnT and the risk of MACE was weakened by the presence of several comorbid conditions. This suggests that the safety of previously validated hs-cTnT diagnostic strategies may be diminished when applied to populations with a high prevalence of comorbid conditions. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Roche Diagnostics