Echocardiography and Electrocardiography in Detecting Atrial Cardiomyopathy: A Promising Path to Predicting Cardioembolic Strokes and Atrial Fibrillation.

(1) Background: Atrial cardiomyopathy constitutes an intrinsically prothrombotic atrial substrate that may promote atrial fibrillation and thromboembolic events, especially stroke, independently of the arrhythmia. Atrial reservoir strain is the echocardiography marker with the most robust evidence supporting its prognostic utility. The main aim of this study is to identify atrial cardiomyopathy by investigating the association between left atrial dysfunction in echocardiography and P-wave abnormalities in the surface electrocardiogram. (2) Methods: This is a community-based, multicenter, prospective cohort study. A randomized sample of 100 patients at a high risk of developing atrial fibrillation were evaluated using diverse echocardiography imaging techniques, and a standard electrocardiogram. (3) Results: Significant left atrial dysfunction, expressed by a left atrial reservoir strain < 26%, showed a relationship with the dilation of the left atrium (p < 0.001), the left atrial ejection fraction < 50% (p < 0.001), the presence of advanced interatrial block (p = 0.032), P-wave voltage in lead I < 0.1 mV (p = 0.008), and MVP ECG score (p = 0.036). (4) Conclusions: A significant relationship was observed between left atrial dysfunction and the presence of left atrial enlargement and other electrocardiography markers; all of them are non-invasive biomarkers of atrial cardiomyopathy.

Blood-biomarkers and devices for atrial fibrillation screening: Lessons learned from the AFRICAT (Atrial Fibrillation Research In CATalonia) study.

BACKGROUND AND OBJECTIVE: AFRICAT is a prospective cohort study intending to develop an atrial fibrillation (AF) screening program through the combination of blood markers, rhythm detection devices, and long-term monitoring in our community. In particular, we aimed to validate the use of NT-proBNP, and identify new blood biomarkers associated with AF. Also, we aimed to compare AF detection using various wearables and long-term Holter monitoring. METHODS: 359 subjects aged 65-75 years with hypertension and diabetes were included in two phases: Phase I (n = 100) and Phase II (n = 259). AF diagnosis was performed by baseline 12-lead ECG, 4 weeks of Holter monitoring (NuuboTM), and/or medical history. An aptamer array including 1310 proteins was measured in the blood of 26 patients. Candidates were selected according to p-value, logFC and biological function to be tested in verification and validation phases. Several screening devices were tested and compared: AliveCor, Watch BP, MyDiagnostick and Fibricheck. RESULTS: AF was present in 34 subjects (9.47%). The aptamer array revealed 41 proteins with differential expression in AF individuals. TIMP-2 and ST-2 were the most promising candidates in the verification analysis, but none of them was further validated. NT-proBNP (log-transformed) (OR = 1.934; p<0.001) was the only independent biomarker to detect AF in the whole cohort. Compared to an ECG, WatchBP had the highest sensitivity (84.6%) and AUC (0.895 [0.780-1]), while MyDiagnostick showed the highest specificity (97.10%). CONCLUSION: The inclusion and monitoring of a cohort of primary care patients for AF detection, together with the testing of biomarkers and screening devices provided useful lessons about AF screening in our community. An AF screening strategy using rhythm detection devices and short monitoring periods among high-risk patients with high NT-proBNP levels could be feasible.

Blood-Based Biomarkers to Search for Atrial Fibrillation in High-Risk Asymptomatic Individuals and Cryptogenic Stroke Patients.

Background: Atrial fibrillation (AF) increases the risk of ischemic stroke in asymptomatic individuals and may be the underlying cause of many cryptogenic strokes. We aimed to test the usefulness of candidate blood-biomarkers related to AF pathophysiology in two prospective cohorts representative of those populations. Methods: Two hundred seventy-four subjects aged 65-75 years with hypertension and diabetes from the AFRICAT cohort, and 218 cryptogenic stroke patients aged >55 years from the CRYPTO-AF cohort were analyzed. AF was assessed by 4 weeks of monitoring with a wearable Holter device (NuuboTM™). Blood was collected immediately before monitoring started. 10 candidate biomarkers were measured by automated immunoassays (Roche, Penzberg) in the plasma of all patients. Univariate and logistic regression analyses were performed in each cohort separately. Results: Atrial fibrillation detection rate was 12.4% (AFRICAT cohort) and 22.9% (CRYPTO-AF cohort). 4 biomarkers were significantly increased in asymptomatic individuals with AF [Troponin-T, Angiopoietin-2 (Ang-2), Endocan, and total N-terminal pro-B type natriuretic peptide (NT-proBNP)] and 7 biomarkers showed significantly higher concentrations in cryptogenic stroke patients with AF detection [growth differentiation factor 15, interleukin 6, Troponin-T, Ang-2, Bone morphogenic protein 10, Dickkopf-related protein 3 (DKK-3), and total NT-proBNP]. The models including Ang-2 and total NT-proBNP [AUC 0.764 (0.665-0.863)], and Ang-2 and DKK-3 [AUC = 0.733 (0.654-0.813)], together with age and sex, showed the best performance to detect AF in high-risk asymptomatic individuals, and in cryptogenic stroke patients, respectively. Conclusion: Blood-biomarkers, in particular, total NT-proBNP, DKK-3, and Ang-2, were associated with AF reflecting two mechanistically different pathways involved in AF pathophysiology (AF stretch and vascular changes). The combination of these biomarkers could be useful in AF screening strategies in the primary care setting and also for searching AF after cryptogenic stroke.

Adjusted Morbidity Groups and Intracerebral Haemorrhage: A Retrospective Primary Care Cohort Study.

BACKGROUND: Intracerebral haemorrhage rates are increasing among highly complex, elderly patients. The main objective of this study was to identify modifiable risk factors of intracerebral haemorrhage. METHODS: Multicentre, retrospective, community-based cohort study was conducted, including patients in the Adjusted Morbidity Group 4 with no history of intracerebral haemorrhage. Cases were obtained from electronic clinical records of the Catalan Institute of Health and were followed up for five years. The primary outcome was the occurrence of intracerebral haemorrhage during the study period. Demographic, clinical and pharmacological variables were included. Logistic regression analyses were carried out to detect prognostic variables for intracerebral haemorrhage. RESULTS: 4686 subjects were included; 170 (3.6%) suffered an intracerebral haemorrhage (85.8/10,000 person-year [95% CI 85.4 to 86.2]). The HAS-BLED score for intracerebral haemorrhage risk detection obtained the best AUC (0.7) when used in the highest complexity level (cut-off point ≥3). Associated independent risk factors were age ≥80 years, high complexity and use of antiplatelet agents. CONCLUSIONS: The Adjusted Morbidity Group 4 is associated with a high risk of intracerebral haemorrhage, particularly for highly complex patients and the use of antiplatelet agents. The risk of bleeding in these patients must be closely monitored.

Complex chronic patients as an emergent group with high risk of intracerebral haemorrhage: an observational cohort study.

BACKGROUND: Demographic aging is a generalised event and the proportion of older adults is increasing rapidly worldwide with chronic pathologies, disability, and complexity of health needs. The intracerebral haemorrhage (ICH) has devastating consequences in high risk people. This study aims to quantify the incidence of ICH in complex chronic patients (CCP). METHODS: This is a multicentre, retrospective and community-based cohort study of 3594 CCPs followed up from 01/01/2013 to 31/12/2017 in primary care without a history of previous ICH episode. The cases were identified from clinical records encoded with ICD-10 (10th version of the International Classification of Diseases) in the e-SAP database of the Catalan Health Institute. The main variable was the ICH episode during the study period. Demographic, clinical, functional, cognitive and pharmacological variables were included. Descriptive and logistic regression analyses were carried out to identify the variables associated with suffering an ICH. The independent risk factors were obtained from logistic regression models, ruling out the variables included in the HAS-BLED score, to avoid duplication effects. Results are presented as odds ratio (OR) and 95% confidence interval (CI). The analysis with the resulting model was also stratified by sex. RESULTS: 161 (4.4%) participants suffered an ICH episode. Mean age 87 ± 9 years; 55.9% women. The ICH incidence density was 151/10000 person-years [95%CI 127-174], without differences by sex. Related to subjects without ICH, presented a higher prevalence of arterial hypertension (83.2% vs. 74.9%; p = 0.02), hypercholesterolemia (55.3% vs. 47.4%, p = 0.05), cardiovascular disease (36.6% vs. 28.9%; p = 0.03), and use of antiplatelet drugs (64.0% vs. 52.9%; p = 0.006). 93.2% had a HAS-BLED score ≥ 3. The independent risk factors for ICH were identified: HAS-BLED ≥3 [OR 3.54; 95%CI 1.88-6.68], hypercholesterolemia [OR 1.62; 95%CI 1.11-2.35], and cardiovascular disease [OR 1.48 IC95% 1.05-2.09]. The HAS_BLED ≥3 score showed a high sensitivity [0.93 CI95% 0.89-0.97] and negative predictive value [0.98 (CI95% 0.83-1.12)]. CONCLUSIONS: In the CCP subgroup the incidence density of ICH was 5-60 times higher than that observed in elder and general population. The use of bleeding risk score as the HAS-BLED scale could improve the preventive approach of those with higher risk of ICH. TRIAL REGISTRATION: This study was retrospectively registered in ClinicalTrials.gov ( NCT03247049 ) on August 11/2017.

Risk of Atrial Fibrillation, Ischemic Stroke and Cognitive Impairment: Study of a Population Cohort ≥65 Years of Age.

PURPOSE: To evaluate a model for calculating the risk of AF and its relationship with the incidence of ischemic stroke and prevalence of cognitive decline. MATERIALS AND METHODS: It was a multicenter, observational, retrospective, community-based study of a cohort of general population ≥6ct 35 years, between 01/01/2016 and 31/12/2018. Setting: Primary Care. Participants: 46,706 people ≥65 years with an active medical history in any of the primary care teams of the territory, information accessible through shared history and without previous known AF. Interventions: The model to stratify the risk of AF (PI) has been previously published and included the variables sex, age, mean heart rate, mean weight and CHA2DS2VASc score. Main measurements: For each risk group, the incidence density/1000 person/years of AF and stroke, number of cases required to detect a new AF, the prevalence of cognitive decline, Kendall correlation, and ROC curve were calculated. RESULTS: The prognostic index was obtained in 37,731 cases (80.8%) from lowest (Q1) to highest risk (Q4). A total of 1244 new AFs and 234 stroke episodes were diagnosed. Q3-4 included 53.8% of all AF and 69.5% of strokes in men; 84.2% of all AF and 85.4% of strokes in women; and 77.4% of cases of cognitive impairment. There was a significant linear correlation between the risk-AF score and the Rankin score (p < 0.001), the Pfeiffer score (p < 0.001), but not NIHSS score (p 0.150). The overall NNS was 1/19. CONCLUSION: Risk stratification allows identifying high-risk individuals in whom to intervene on modifiable risk factors, prioritizing the diagnosis of AF and investigating cognitive status.

Incidence and Risk Assessment for Atrial Fibrillation at 5 Years: Hypertensive Diabetic Retrospective Cohort.

(1) Background: The link between diabetes and hypertension is mutual and reciprocal, increasing the risks for the development of atrial fibrillation (AF). The main objective was to develop a prediction model for AF in a population with both diabetes and hypertension at five years of follow-up. (2) Methods: A multicenter and community-based cohort study was undertaken of 8237 hypertensive diabetic patients without AF between 1 January 2103 and 31 December 2017. Multivariate Cox proportional-hazards regression models were used to identify predictors AF and to stratify risk scores by quartiles. (3) Results: AF incidence was 10.5/1000 people/years (95% confidence interval (CI) 9.5-11.5), higher in men. The independent prognostic factors identified: age (hazard ratio (HR) 1.07 95% CI 1.05-1.09, p < 0.001), weight (HR 1.03 95% CI 1.02-1.04, p < 0.001), CHA2DS2VASc score (HR 1.57 95% CI 1.16-2.13, p = 0.003) and female gender (HR 0.55 95% CI 0.37-0.82, p = 0.004). Q4 (highest-risk group for AF) had the highest AF incidence, stroke and mortality, and the smallest number needed to screen to detect one case of AF. (4) Conclusions: Risk-based screening for AF should be used in high cardiovascular risk patients as the hypertensive diabetics, for treatment of modifiable cardiovascular risk, and monitoring AF detection.

Results, barriers and enablers in atrial fibrillation case finding: barriers in opportunistic atrial fibrillation case finding-a cross-sectional study.

BACKGROUND: Atrial fibrillation (AF) is often asymptomatic, and screening is not routinely undertaken. OBJECTIVE: Evaluate the feasibility and effectiveness of a population-based case finding program and to identify the enablers of and/or barriers to its implementation. METHODS: We conducted a cross-sectional study of a health care case finding program for AF from 1 January 2016, to 31 December 2017, that included 48 336 people ≥60 years of age in the region of Terresde l'Ebre (Catalonia, Spain). We analysed the effect on the prevalence of AF and, stratified by age, on the incidence of new diagnoses of AF. We assessed the sociodemographic and clinical variables related to the realization of a case finding. RESULTS: A total of 32 090 (62.4%) people were screened for AF. We observed a significant increase in the AF prevalence after 2 years of program intervention (5.9-7.7%; P < 0.001). The detection of new AF cases was significantly higher in the case finding group across the whole of the age range, and 765 (2.6%) new AF cases were diagnosed using case finding. The factors that were significantly associated with an underuse of case finding were: age <70 years, urban residence, institutionalized status, Pfeiffer score ≥2, Charlson score >3 and number of visits <7/year. CONCLUSIONS: A health care program of case finding is feasible and is associated with a significant increase in the prevalence and incidence of AF. The results depend on factors such as the ease of access to health care, age, place of residence and comorbidities.

Risk of Long-Term Mortality for Complex Chronic Patients with Intracerebral Hemorrhage: A Population-Based e-Cohort Observational Study.

INTRODUCTION: Over recent years there has been growing evidence of increased risk of mortality associated with hemorrhagic stroke among older patients. The main objective of this study is to propose and validate a prognostic life table for complex chronic patients after an intracerebral hemorrhage (ICH) episode in primary care settings. METHODS: This was a multicenter and retrospective study (April 1, 2006-December 31, 2016) of a cohort from the general population presenting an episode of ICH from which a predictive model of mortality was obtained using a Cox proportional hazards regression model. In addition, Kaplan-Meier survival curves, the log-rank test, receiver operating characteristic (ROC) curves, and area under the ROC curve (AUC) were used to evaluate the ability to stratify patients according to vital prognosis. We proceeded to external validation of the model through prospective monitoring (January 1, 2013-December 31, 2017) of the population of complex chronic patients with an episode of ICH. RESULTS: A total of 3594 people aged ≥ 65 years were identified as complex chronic patients (women 55.9%; mean age, 86.1 ± 8.4 years) of whom 161 suffered hemorrhagic stroke during the study period (January 1, 2013-December 31, 2017). The primary outcome was death from any cause within 5 years of follow-up after an ICH episode. The independent prognostic factors of mortality were age > 80 years (HR 1.048, 95% CI 1.021-1.076, p < 0.001) and HAS-BLED score (HR 1.369, 95% CI 1.057-1.774, p = 0.017). Compared to the general population, the incidence density/1000 person per year (15 vs 0.22) was significantly higher with a significantly lower annual lethality rate (17% vs 49.2%); and both the prognostic factors and the risk of stratified mortality showed different epidemiological patterns. The internal validation of the model was optimal (log-rank < 0.0001) in the general population, but its external validation was not significant in the complex chronic patient population (log-rank p = 0.104). CONCLUSIONS: The ICH-AP is a clinical scale that can improve the prognostic prediction of mortality in primary care after an episode of ICH in the general population, but it was not significant in its external validation in a population of complex chronic patients. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03247049.

N-Terminal Pro B-Type Natriuretic Peptide's Usefulness for Paroxysmal Atrial Fibrillation Detection Among Populations Carrying Cardiovascular Risk Factors.

Background: Atrial fibrillation (AF) systematic screening studies have not shown a clear usefulness in stroke prevention, as AF might present as paroxysmal and asymptomatic. This study aims to determine the usefulness of some blood-biomarkers to identify paroxysmal atrial fibrillation in the context of a screening programme. Methods: A total of 100 subjects aged 65-75 years with hypertension and diabetes were randomly selected. AF was assessed by conventional electrocardiogram (ECG) and 4 weeks monitoring with a wearable Holter device (Nuubo™). N-terminal pro B-type natriuretic peptide (NT-proBNP), apolipoprotein CIII (ApoC-III), von Willebrand factor (vWF), ADAMTS13, urokinase plasminogen activator surface receptor (uPAR), and urokinase plasminogen activator (uPA) were determined in serum/plasma samples and the levels were compared depending on AF presence and mode of detection. Results: The AF prevalence in the studied population was found to be 20%. In seven subjects, AF was only detected after 1 month of Holter monitoring (hAF group). NT-proBNP levels were higher in subjects with AF compared with subjects with no AF (p < 0.0001), even when only taking into account the hAF group (p = 0.031). No significant differences were found in the other biomarkers. The NT-proBNP >95 pg/ml cut-off showed high sensitivity and specificity to detect AF (95%, 66.2%) or hAF (85.72%, 66.2%) and was found to be an independent predictor of AF and hAF in a logistic regression analysis. NT-proBNP correlated with AF burden (r = 0.597, p = 0.024). Conclusion: NT-proBNP was elevated in AF cases not identified by ECG; thus, it may be used as a screening biomarker in asymptomatic high-risk populations, with a promising cut-off point of 95 pg/ml that requires further validation.

Long-Term Survival After Stroke According to Reperfusion Therapy, Cardiovascular Therapy and Gender.

BACKGROUND: A wide variety of factors influence stroke prognosis, including age, stroke severity and comorbid conditions; but most current information about outcomes and safety is derived from patients at 3 - 12 months and mostly coming from the hospital activity. The aim of this study is to evaluate whether treatment strategies have a differential impact on long-survival after acute ischemic stroke among men versus women. METHODS: Acute ischemic stroke patients identified from the population-based register between January 1, 2011 and December 31, 2012 were included, and they were classified into: 1) Acute ischemic stroke + intravenous thrombolysis (group I); 2) Acute ischemic stroke + mechanical thrombectomy with or without intravenous thrombolysis (group II); 3) Acute ischemic stroke + medical therapy alone (no reperfusion therapies) (group III). Follow-up went through up until December 2016. The probability of survival was estimated by the Kaplan-Meier method, and the hazard ratio was obtained by using the Cox proportional hazard regression models. Mortality was interpreted as overall mortality. RESULTS: A total of 14,368 cases (men 50.1%), 77.1 ± 11.0 years old were included. There was higher survival among those treated with intravenous thrombolysis (P < 0.001); women treated with thrombectomy (P < 0.001); and women < 80 years old without reperfusion therapy. The most common medications were antiplatelets (52.8%), associated with lower survival (P < 0.001); and statins (46.5%), associated with higher survival. The regression model produced the following independent outcome variables associated to mortality: anticoagulant hazard ratio (HR) 1.53 (95% confidence interval (95% CI): 1.44 - 1.63, P < 0.001), diuretics HR 1.71 (95% CI: 1.63 - 1.79, P < 0.001), antiplatelet HR 1.49 (95% CI: 1.42 - 1.56, P < 0.001), statins HR 0.73 (95% CI: 0.70 - 0.77; P < 0.001), angiotensin II receptor antagonists HR 0.93 (95% CI: 0.89 - 0.98, P = 0.008) and reperfusion therapy HR 0.88 (95% CI: 0.81 - 0.97, P = 0.009). CONCLUSIONS: Men and women have different prognoses after revascularization treatment for acute ischemic stroke. Under 80 years old the women appear to have a better outcome than men when treated with thrombolysis therapy and/or catheter-based thrombectomy. The chronic cardiovascular pharmacotherapy must be evaluated whether they should be included as factors in the decision to reperfusion.