Machine Learning Modeling to Predict Atrial Fibrillation Detection in Embolic Stroke of Undetermined Source Patients.

BACKGROUND: In patients with embolic stroke of undetermined source (ESUS), occult atrial fibrillation (AF) has been implicated as a key source of cardioembolism. However, only a minority acquire implantable cardiac loop recorders (ILRs) to detect occult paroxysmal AF, partly due to financial cost and procedural inconvenience. Without the initiation of appropriate anticoagulation, these patients are at risk of increased ischemic stroke recurrence. Hence, cost-effective and accurate methods of predicting AF in ESUS patients are highly sought after. OBJECTIVE: We aimed to incorporate clinical and echocardiography data into machine learning (ML) algorithms for AF prediction on ILRs in ESUS. METHODS: This was a single-center cohort study that included 157 consecutive patients diagnosed with ESUS from October 2014 to October 2017 who had ILR evaluation. We developed four ML models, with hyperparameters tuned, to predict AF detection on an ILR. RESULTS: The median age of the cohort was 67 (IQR 59-74) years old and the median monitoring duration was 1051 (IQR 478-1287) days. Of the 157 patients, 32 (20.4%) had occult AF detected on the ILR. Support vector machine predicted for AF with a 95% confidence interval area under the receiver operating characteristic curve (AUC) of 0.736-0.737, multilayer perceptron with an AUC of 0.697-0.708, XGBoost with an AUC of 0.697-0.697, and random forest with an AUC of 0.663-0.674. ML feature importance found that age, HDL-C, and admitting heart rate were important non-echocardiography variables, while peak mitral A-wave velocity and left atrial volume were important echocardiography parameters aiding this prediction. CONCLUSION: Machine learning modeling incorporating clinical and echocardiographic variables predicted AF in ESUS patients with moderate accuracy.

Left Ventricular Diastolic Dysfunction Is Associated with Poor Functional Outcomes after Endovascular Thrombectomy.

INTRODUCTION: With the advent of endovascular thrombectomy (ET), patients with acute ischaemic strokes (AIS) with large vessel occlusion (LVO) have seen vast improvements in treatment outcomes. Left ventricular diastolic dysfunction (LVDD) has been shown to herald poorer prognosis in conditions such as myocardial infarction. However, whether LVDD is related to functional recovery and outcomes in ischaemic stroke remains unclear. We studied LVDD for possible relation with clinical outcomes in patients with LVO AIS who underwent ET. METHODS: We studied a retrospective cohort of 261 LVO AIS patients who had undergone ET at a single comprehensive stroke centre and correlated LVDD to short-term mortality (in-hospital death) as well as good functional recovery defined as modified Rankin Scale of 0-2 at 3 months. RESULTS: The study population had a mean age of 65-years-old and were predominantly male (54.8%). All of the patients underwent ET with 206 (78.9%) achieving successful reperfusion. Despite this, 25 (9.6%) patients demised during the hospital admission and 149 (57.1%) did not have good function recovery at 3 months. LVDD was present in 82 (31.4%) patients and this finding indicated poorer outcomes in terms of functional recovery at 3 months (OR 2.18, 95% CI 1.04-4.54, p = 0.038) but was not associated with increased in-hospital mortality (OR 2.18, 95% CI 0.60-7.99, p = 0.240) after adjusting for various confounders. CONCLUSION: In addition to conventional echocardiographic indices such as left ventricular ejection fraction, LVDD may portend poorer outcomes after ET, and this relationship should be investigated further.

Association Between Calcium Supplementation and the Risk of Cardiovascular Disease and Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Some observational studies and randomised controlled trials (RCTs) have reported an association between calcium supplementation and increased risk of cardiovascular disease. Previous meta-analyses on the topic, based on data from RCTs and observational studies, have contradictory findings. This meta-analysis was conducted to determine the difference in associated risks of calcium supplementation with cardiovascular disease and stroke in RCTs. METHODS: Relevant studies published from database inception to 6 August 2021 were sourced from PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials. Any RCTs focusing on the relationship between calcium supplementation and incidence of cardiovascular disease or stroke were included. Articles were screened independently by two authors, according to the PICO criteria, with disagreements resolved by a third author. RESULTS: Twelve RCTs were included in the meta-analysis. Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and all-cause/cardiovascular mortality. Subgroup analysis focusing on calcium monotherapy/calcium co-therapy with vitamin D, female sex, follow-up duration, and geographical region did not affect the findings. CONCLUSION: Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and cardiovascular/all-cause mortality. Further studies are required to examine and understand these associations.

Acute Myocardial Infarction and Risk of Cognitive Impairment and Dementia: A Review.

Cognitive impairment (CI) shares common cardiovascular risk factors with acute myocardial infarction (AMI), and is increasingly prevalent in our ageing population. Whilst AMI is associated with increased rates of CI, CI remains underreported and infrequently identified in patients with AMI. In this review, we discuss the evidence surrounding AMI and its links to dementia and CI, including pathophysiology, risk factors, management and interventions. Vascular dysregulation plays a major role in CI, with atherosclerosis, platelet activation, microinfarcts and perivascular inflammation resulting in neurovascular unit dysfunction, disordered homeostasis and a dysfunctional neurohormonal response. This subsequently affects perfusion pressure, resulting in enlarged periventricular spaces and hippocampal sclerosis. The increased platelet activation seen in coronary artery disease (CAD) can also result in inflammation and amyloid-ß protein deposition which is associated with Alzheimer's Dementia. Post-AMI, reduced blood pressure and reduced left ventricular ejection fraction can cause chronic cerebral hypoperfusion, cerebral infarction and failure of normal circulatory autoregulatory mechanisms. Patients who undergo coronary revascularization (percutaneous coronary intervention or bypass surgery) are at increased risk for post-procedure cognitive impairment, though whether this is related to the intervention itself or underlying cardiovascular risk factors is debated. Mortality rates are higher in dementia patients with AMI, and post-AMI CI is more prevalent in the elderly and in patients with post-AMI heart failure. Medical management (antiplatelet, statin, renin-angiotensin system inhibitors, cardiac rehabilitation) can reduce the risk of post-AMI CI; however, beta-blockers may be associated with functional decline in patients with existing CI. The early identification of those with dementia or CI who present with AMI is important, as subsequent tailoring of management strategies can potentially improve outcomes as well as guide prognosis.

Left Ventricular Ejection Fraction Association with Acute Ischemic Stroke Outcomes in Patients Undergoing Thrombolysis.

(1) Background: Little is known about how left ventricular systolic dysfunction (LVSD) affects functional and clinical outcomes in acute ischemic stroke (AIS) patients undergoing thrombolysis; (2) Methods: A retrospective observational study conducted between 2006 and 2018 included 937 consecutive AIS patients undergoing thrombolysis. LVSD was defined as left ventricular ejection fraction (LVEF) < 50%. Univariate and multivariate binary logistic regression analysis was performed for demographic characteristics. Ordinal shift regression was used for functional modified Rankin Scale (mRS) outcome at 3 months. Survival analysis of mortality, heart failure (HF) admission, myocardial infarction (MI) and stroke/transient ischemic attack (TIA) was evaluated with a Cox-proportional hazards model; (3) Results: LVSD patients in comparison with LVEF ≥ 50% patients accounted for 190 and 747 patients, respectively. LVSD patients had more comorbidities including diabetes mellitus (100 (52.6%) vs. 280 (37.5%), p < 0.001), atrial fibrillation (69 (36.3%) vs. 212 (28.4%), p = 0.033), ischemic heart disease (130 (68.4%) vs. 145 (19.4%), p < 0.001) and HF (150 (78.9%) vs. 46 (6.2%), p < 0.001). LVSD was associated with worse functional mRS outcomes at 3 months (adjusted OR 1.41, 95% CI 1.03-1.92, p = 0.030). Survival analysis identified LVSD to significantly predict all-cause mortality (adjusted HR [aHR] 3.38, 95% CI 1.74-6.54, p < 0.001), subsequent HF admission (aHR 4.23, 95% CI 2.17-8.26, p < 0.001) and MI (aHR 2.49, 95% CI 1.44-4.32, p = 0.001). LVSD did not predict recurrent stroke/TIA (aHR 1.15, 95% CI 0.77-1.72, p = 0.496); (4) Conclusions: LVSD in AIS patients undergoing thrombolysis was associated with increased all-cause mortality, subsequent HF admission, subsequent MI and poorer functional outcomes, highlighting a need to optimize LVEF.

The impact of sodium-glucose cotransporter inhibitors on blood pressure: a meta-analysis and metaregression of 111 randomized-controlled trials.

OBJECTIVE: Multiple trials on sodium-glucose cotransporter (SGLT) inhibitors have been performed recently demonstrating blood pressure (BP) reduction benefits in both diabetic and nondiabetic patients. Hence, we conducted a systematic review and meta-analysis to determine the effect of different SGLT inhibitors on BP in both patients with and without diabetes mellitus. METHODS: Four electronic databases (PubMed, Embase, Cochrane, and SCOPUS) were searched on 4 November 2021 for articles published from 1 January 2000 up to 21 November 2021, for studies evaluating the BP effects of SGLT inhibitors. Pair-wise meta-analysis and random effects metaregression models were utilized. RESULTS: In total, 111 studies examining SBP (108 studies, 104 304 patients) and/or DBP (82 studies, 74 719 patients) were included. In patients with diabetes, the random effects model demonstrated SGLT inhibitor produced a mean reduction in SBPs of -3.46 mmHg (95% confidence interval: -3.83, -3.09) compared with placebo. There were no statistically significant changes in BP among patients without diabetes. Drug response relationship was not observed in SGLT inhibitors and BP, except for Canagliflozin and DBP. CONCLUSION: Sodium-glucose cotransporter 2 inhibitors and combined sodium-glucose cotransporter 1/2 inhibitors produced small reductions in BP in patients with diabetes.

Comparison of the Efficacy and Safety of Non-vitamin K Antagonist Oral Anticoagulants with Warfarin in Atrial Fibrillation Patients with a History of Bleeding: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with atrial fibrillation (AF) require oral anticoagulation to prevent ischemic stroke. However, oral anticoagulation may cause bleeding, and patients with AF and a history of bleeding were excluded from pivotal trials comparing non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin. We therefore aimed to assess the efficacy and safety of NOACs compared with warfarin in patients with AF and a history of bleeding. METHODS: We conducted a systematic review of retrospective studies and clinical trials using the PubMed, EMBASE, SCOPUS, Cochrane Library, and Web of Science databases to May 2021. RESULTS: Overall, 56,697 patients from six studies were included. NOACs significantly reduced the risk of ischemic stroke (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.59-0.91; p = 0.005), fatal ischemic stroke (HR 0.49, 95% CI 0.39-0.61; p < 0.001), all-cause mortality (HR 0.70, 95% CI 0.50-0.98; p = 0.04), major bleeding events (HR 0.75, 95% CI 0.67-0.84; p < 0.001), intracranial hemorrhage (ICH; HR 0.63, 95% CI 0.48-0.82; p < 0.001), fatal ICH (HR 0.33, 95% CI 0.20-0.56, p < 0.001), and gastrointestinal bleeding (HR 0.83, 95% CI 0.72-0.96; p = 0.01). CONCLUSIONS: NOACs showed better efficacy and safety profile compared with warfarin in patients with AF and a history of bleeding. Randomized controlled trials are warranted to validate these findings.

Utility of conventional clinical risk scores in a low-risk COVID-19 cohort.

BACKGROUND: Several specific risk scores for Coronavirus disease 2019 (COVID-19) involving clinical and biochemical parameters have been developed from higher-risk patients, in addition to validating well-established pneumonia risk scores. We compared multiple risk scores in predicting more severe disease in a cohort of young patients with few comorbid illnesses. Accurately predicting the progression of COVID-19 may guide triage and therapy. METHODS: We retrospectively examined 554 hospitalised COVID-19 patients in Singapore. The CURB-65 score, Pneumonia Severity Index (PSI), ISARIC 4C prognostic score (4C), CHA2DS2-VASc score, COVID-GRAM Critical Illness risk score (COVID-GRAM), Veterans Health Administration COVID-19 index for COVID-19 Mortality (VACO), and the "rule-of-6" score were compared for three performance characteristics: the need for supplemental oxygen, intensive care admission and mechanical ventilation. RESULTS: A majority of patients were young (≤ 40 years, n = 372, 67.1%). 57 (10.3%) developed pneumonia, with 16 (2.9% of study population) requiring supplemental oxygen. 19 patients (3.4%) required intensive care and 2 patients (0.5%) died. The clinical risk scores predicted patients who required supplemental oxygenation and intensive care well. Adding the presence of fever to the CHA2DS2-VASc score and 4C score improved the ability to predict patients who required supplemental oxygen (c-statistic 0.81, 95% CI 0.68-0.94; and 0.84, 95% CI 0.75-0.94 respectively). CONCLUSION: Simple scores including well established pneumonia risk scores can help predict progression of COVID-19. Adding the presence of fever as a parameter to the CHA2DS2-VASc or the 4C score improved the performance of these scores in a young population with few comorbidities.

Association of Global Cardiac Calcification with Atrial Fibrillation and Recurrent Stroke in Patients with Embolic Stroke of Undetermined Source.

BACKGROUND: Calcium deposits in the heart have been associated with cardiovascular events, mortality, stroke, and atrial fibrillation (AF). However, there is no accepted standard method for scoring cardiac calcifications. Existing methods have also not been validated for the assessment of patients with embolic stroke of undetermined source (ESUS). The aim of this study was to evaluate the association of various cardiac calcification scores with new-onset AF and stroke recurrence in a cohort of patients with ESUS. METHODS: In this study, 181 consecutive patients with stroke diagnosed with ESUS were identified and evaluated. They were followed for new-onset AF and ischemic stroke recurrence for a median duration of 2.1 years. Various echocardiographic cardiac calcification scores were assessed on transthoracic echocardiography performed during the evaluation of ESUS and subsequently assessed for their relation to AF detection and recurrent stroke. The echocardiographic calcium scores assessed were the (1) global cardiac calcium score (GCCS), (2) echocardiographic calcium score (eCS), (3) echocardiographic calcification score, (4) echocardiographic composite cardiac calcium score, and (5) total heart calcification score. Only two of these scoring schemes, GCCS and eCS, quantified the cardiac calcium burden. RESULTS: Higher calcium scores as measured by GCCS and eCS were found to be significantly associated with subsequent AF detection as well as recurrent ischemic stroke in patients with ESUS. The association with recurrent stroke remained significant even after adjustment for comorbidities and AF. CONCLUSIONS: Higher cardiac calcification measured using the GCCS and eCS is independently associated with AF detection and recurrent ischemic stroke in patients with ESUS, and these scores can be useful markers for further risk stratification in patients with ESUS.

Demographic shift in COVID-19 patients in Singapore from an aged, at-risk population to young migrant workers with reduced risk of severe disease.

OBJECTIVES: The vast majority of COVID-19 cases in Singapore have occurred amongst migrant workers. This paper examined trends in the hospitalised cases and tested the assumption that the low severity of disease was related to the relatively young affected population. METHODS: All patients with PCR-positive SARS-CoV-2 admitted from February to April 2020 were divided into: (i) imported cases, (ii) locally-transmitted cases outside migrant worker dormitories and (iii) migrant worker dormitory cases. They were examined for underlying comorbidities, clinical progress and outcomes. RESULTS: Imported cases (n = 29) peaked in mid-March 2020, followed by local cases (n = 100) in mid-April 2020; migrant worker cases (n = 425) continued to increase in late April 2020. Migrant worker cases were younger, had few medical comorbidities and less severe disease. As the migrant worker cases increased, the proportion of patients with pneumonia decreased, whilst patients presenting earlier in their illness and asymptomatic disease became more common. CONCLUSION: Singapore experienced a substantial shift in the population at risk of severe COVID-19. Successful control in the community protected an aging population. Large migrant worker dormitory outbreaks occurred, but the disease incurred was less severe, resulting in Singapore having one of the lowest case fatality rates in the world.

Association of Electrocardiographic P-Wave Markers and Atrial Fibrillation in Embolic Stroke of Undetermined Source.

BACKGROUND: Several P-wave indices are thought to represent underlying atrial remodeling and have been associated with ischaemic stroke even in the absence of atrial fibrillation (AF). However, the utility of these P-wave indices in predicting outcomes in patients with embolic stroke of undetermined source (ESUS) has not been studied. The aim of this study is to examine these different P-wave indices towards predicting new-onset AF and stroke recurrence in a cohort of patients with ESUS, thereby demonstrating the value of these electrocardiographic markers for stroke risk stratification. METHODS: Between October 2014 and October 2017, consecutive patients diagnosed with ESUS were followed for new-onset AF and ischaemic stroke recurrence. The various P-wave indices, namely, the P-terminal force in the precordial lead V1 (PTFV1), P-wave duration, P-wave dispersion, interatrial blocks, and P-wave axis, were assessed on the initial electrocardiogram on presentation and studied for their relation to eventual AF detection and recurrent stroke. RESULTS: 181 ischaemic stroke patients with ESUS were recruited and followed up for a median duration of 2.1 years. An abnormal PTFV1 was associated with occult AF detection but not with recurrent ischaemic strokes. No significant association was observed between the other P-wave indices with either occult AF or stroke recurrence. CONCLUSION: PTFV1 is associated with AF detection but not recurrent strokes in ESUS patients and can be a useful electrocardiographic marker for further risk stratification in ESUS patients.

Left ventricular pacing in patients with preexisting tricuspid valve disease.

BACKGROUND: Conventional right ventricular (RV) pacing is increasingly recognised to cause tricuspid valve (TV) injury or dysfunction, in part due to the need to pass the lead through the valve. This may be especially problematic in patients with preexisting TV disease or prior TV surgery. An alternative in this situation is to implant a left ventricular (LV) lead instead of ventricular pacing. METHODS: We performed a single-center retrospective analysis of 26 patients with tricuspid valve surgery/disease who received a LV pacing lead in the coronary veins to avoid crossing the tricuspid valve, with or without a right atrial lead. A matched control population was obtained from patients receiving conventional right ventricular pacing and outcomes were compared. Main outcomes of interest were lead stability, electrical lead parameters and change in echocardiographic parameters such as left ventricular ejection fraction (LVEF) during long-term follow-up. RESULTS: Successful left ventricular pacing was established in 25 out of the 26 cases with one case converted to a RV lead due to lead dislodgement. During the 2.96 ± 1.0 year follow-up, 24 of 25 (96.0%) leads were functional with stable pacing and sensing parameters, and 1 of 25 (4.0%) was extracted for due to device infection following an episode of thrombophlebitis. CONCLUSION: We conclude that in patients with existing tricuspid valve disease or surgery, ventricular pacing via the coronary veins is a feasible, safe, and reliable alternative to right ventricular pacing.