Showing papers by "Alonso Pedrote published in 2022"

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

Abstract: 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.

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

Abstract: 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.

Automated quantification and identification of decremental response after extrastimulus: validation of a novel software

Abstract: Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Junta de Andalucia Automatic identification of myocardial electrograms (EGMs) with decremental conduction (DC) is a promising field in catheter ablation procedures, allowing the identification of the critical isthmus of tachycardias with re-entry mechanisms. In this work, a novel artificial intelligence (AI)-based software was developed for the automatic analysis of delays between evoked responses in the coronary sinus (CS), allowing signal quantification. Atrioventricular (AV) and ventriculoatrial (VA) conduction was analysed in coronary sinus signals obtained from patients undergoing electrophysiological study. A simple pacing (S=400-600ms) and extra-stimulus protocol (S2=ERP + 20-60ms) were used in all cases. An AI-based algorithm was developed for EGM delineation with the objective of localising the onsets and offsets of each independent local and far field activations. The algorithm consisted in several steps. Firstly, an AI-based QRS detector was employed (Figure 1A). Secondly, the located QRS’ were used alongside another AI model to delineate the EGMs corresponding to all bipolar electrodes in the CS (Figure 1B). Thirdly, majority voting is performed on the delineations to obtain an overall prediction for all CS electrodes (Figure 1C). Fourthly, the predictions are cleaned and a rule-based algorithm is employed to automatically exclude faulty registries (e.g. loss of capture or AV/VA block after S2). Finally, the determination of decremental response is performed by computing the time difference between the last paced beat and the S2 extrastimulus. This was measured using the onsets of morphologically similar activations in the trace, correcting for misalignments. A decremental response was defined as a difference >10 ms between the AV/VA interval during the S1 drive and the same interval immediately after the S2. Four experts validated results of the automated analysis. 321 tracings from 50 patients were analysed. 81 tracings were automatically excluded due to loss of capture or AV/VA block after S2. The AV/VA interval was automatically annotated in 236 EGMs. 192 tracings exhibited decremental conduction properties, whereas 48 tracings showed non-decremental AV or VA conduction due to accessory pathways. Automatic analysis accurately classified 191 tracings as decremental (93.75% sensitivity, 91.47% specificity) and 45 tracings as non-decremental (85.42% sensitivity, 98.53% specificity). AI-based algorithms are able to produce objective quantifications over real-world data, discriminating between local and far field signals and accurately identifying EGMs with decremental evoked response. Automated data analysis can accelerate research and reduce clinical workload. Moreover, a quantification-based approach can be employed in many other applications. Validation of this software on ventricular signals could facilitate ventricular tachycardia substrate ablation procedures.

New KCNQ1 c.604+1G>C variant associated with Jervell-Lange Nielsen syndrome in homozygosity and compound heterozygosity.

Abstract: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome. Most patients are empirically treated with beta-blockers and antiplatelet drugs. The Beta-blockers and Antiplatelet agents in patients with Spontaneous Coronary Artery Dissection (BA-SCAD) is an academic, pragmatic, prospective, randomized, open-label, blinded-endpoint clinical trial, performed under the auspices of the Spanish Society of Cardiology, to assess the efficacy of pharmacological therapy in patients with SCAD.Using a 2 x 2 factorial design, 600 patients will be randomized (1:1/1:1) to: a) beta-blockers (yes/no) and b) “short” (1 month) vs “prolonged” (12 months) antiplatelet therapy. Only patients with preserved left ventricular ejection fraction will be randomized to beta-blockers (yes/no) because patients with reduced left ventricular ejection fraction will receive beta-blockers according to current guidelines. Similarly, only conservatively managed patients (ie, no coronary intervention) will be randomized to the antiplatelet stratum, as patients requiring coronary interventions will receive 1-year dual antiplatelet therapy. The primary efficacy endpoint includes a composite of death, myocardial infarction, stroke, coronary revascularization, recurrent SCAD, and unplanned hospitalization for acute coronary syndrome or heart failure at 1 year. The primary safety endpoint will be bleeding. All patients will be clinically followed up yearly. A comprehensive set of additional substudies (clinical, imaging, revascularization, biomarkers, inflammatory, immunologic, pharmacogenetics, and genetic) will be conducted to ensure a holistic view of this unique and challenging clinical entity.The results of the BA-SCAD randomized clinical trial will advance our knowledge in the treatment of patients with SCAD.The study was registered at ClinicalTrials.gov (Identifier: NCT04850417).La disección coronaria espontánea (DCE) es una causa rara de síndrome coronario agudo. La mayor parte de los pacientes con DCE son tratados empíricamente con bloqueadores beta (BB) y antiagregantes plaquetarios (AP). El estudio BA-SCAD (bloqueadores beta y agentes antiplaquetarios en pacientes con disección coronaria espontánea) es un ensayo clínico académico, pragmático, diseñado con metodología PROBE (prospective randomized open blinded endpoint), con el patrocinio de la Sociedad Española de Cardiología, para conocer la eficacia del tratamiento farmacológico en pacientes con DCE.Mediante un diseño factorial 2 × 2, se aleatorizará a 600 pacientes (1:1/1:1) a: a) BB (sí/no) y b) tratamiento con AP «corto» (1 mes) frente a tratamiento antiagregante plaquetario doble y «prolongado» (12 meses). Se aleatorizará a BB (sí/no) solo a los pacientes con fracción de eyección del ventrículo izquierdo conservada, ya que a los pacientes con fracción de eyección reducida se los tratará con BB de acuerdo con las guías actuales. De modo similar, se aleatorizará al estrato de AP solo a los pacientes en tratamiento conservador (sin revascularización), ya que los que requieran intervención coronaria recibirán tratamiento antiagregante plaquetario doble durante 1 año. El objetivo primario de valoración incluye muerte, infarto de miocardio, accidente cerebrovascular, revascularización coronaria, DCE recurrente y hospitalización no planeada por síndrome coronario agudo o insuficiencia cardiaca al año de seguimiento. El objetivo de seguridad es la hemorragia. Todos los pacientes serán seguidos anualmente. Se desarrollará un programa exhaustivo de subestudios adicionales (clínicos, de imagen, de revascularización, de biomarcadores, inflamatorios, inmunológicos, farmacogenéticos y genéticos) para garantizar una visión completa de esta entidad tan especial y compleja.Los resultados del estudio clínico aleatorizado BA-SCAD mejorarán nuestro conocimiento sobre el tratamiento de los pacientes con DCE.El estudio se registró en ClinicalTrials.gov (Identifier: NCT04850417).