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1.
Catheter Cardiovasc Interv ; 102(1): 80-90, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37191312

RESUMEN

BACKGROUND: We aimed to develop a machine learning algorithm to predict the presence of a culprit lesion in patients with out-of-hospital cardiac arrest (OHCA). METHODS: We used the King's Out-of-Hospital Cardiac Arrest Registry, a retrospective cohort of 398 patients admitted to King's College Hospital between May 2012 and December 2017. The primary outcome was the presence of a culprit coronary artery lesion, for which a gradient boosting model was optimized to predict. The algorithm was then validated in two independent European cohorts comprising 568 patients. RESULTS: A culprit lesion was observed in 209/309 (67.4%) patients receiving early coronary angiography in the development, and 199/293 (67.9%) in the Ljubljana and 102/132 (61.1%) in the Bristol validation cohorts, respectively. The algorithm, which is presented as a web application, incorporates nine variables including age, a localizing feature on electrocardiogram (ECG) (≥2 mm of ST change in contiguous leads), regional wall motion abnormality, history of vascular disease and initial shockable rhythm. This model had an area under the curve (AUC) of 0.89 in the development and 0.83/0.81 in the validation cohorts with good calibration and outperforms the current gold standard-ECG alone (AUC: 0.69/0.67/0/67). CONCLUSIONS: A novel simple machine learning-derived algorithm can be applied to patients with OHCA, to predict a culprit coronary artery disease lesion with high accuracy.


Asunto(s)
Reanimación Cardiopulmonar , Enfermedad de la Arteria Coronaria , Paro Cardíaco Extrahospitalario , Humanos , Paro Cardíaco Extrahospitalario/diagnóstico , Paro Cardíaco Extrahospitalario/terapia , Estudios Retrospectivos , Resultado del Tratamiento , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Angiografía Coronaria , Algoritmos
2.
Circ Res ; 120(2): 418-435, 2017 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-28104774

RESUMEN

Over the last few years, several groups have evaluated the potential of microRNAs (miRNAs) as biomarkers for cardiometabolic disease. In this review, we discuss the emerging literature on the role of miRNAs and other small noncoding RNAs in platelets and in the circulation, and the potential use of miRNAs as biomarkers for platelet activation. Platelets are a major source of miRNAs, YRNAs, and circular RNAs. By harnessing multiomics approaches, we may gain valuable insights into their potential function. Because not all miRNAs are detectable in the circulation, we also created a gene ontology annotation for circulating miRNAs using the gene ontology term extracellular space as part of blood plasma. Finally, we share key insights for measuring circulating miRNAs. We propose ways to standardize miRNA measurements, in particular by using platelet-poor plasma to avoid confounding caused by residual platelets in plasma or by adding RNase inhibitors to serum to reduce degradation. This should enhance comparability of miRNA measurements across different cohorts. We provide recommendations for future miRNA biomarker studies, emphasizing the need for accurate interpretation within a biological and methodological context.


Asunto(s)
Plaquetas/metabolismo , MicroARNs/sangre , Activación Plaquetaria/fisiología , Trombosis/sangre , Animales , Coagulación Sanguínea/fisiología , Humanos , MicroARNs/genética , ARN no Traducido/sangre , ARN no Traducido/genética , Trombosis/diagnóstico , Trombosis/genética
3.
Circ Res ; 118(3): 420-432, 2016 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-26646931

RESUMEN

RATIONALE: Platelets shed microRNAs (miRNAs). Plasma miRNAs change on platelet inhibition. It is unclear whether plasma miRNA levels correlate with platelet function. OBJECTIVE: To link small RNAs to platelet reactivity. METHODS AND RESULTS: Next-generation sequencing of small RNAs in plasma revealed 2 peaks at 22 to 23 and 32 to 33 nucleotides corresponding to miRNAs and YRNAs, respectively. Among YRNAs, predominantly, fragments of RNY4 and RNY5 were detected. Plasma miRNAs and YRNAs were measured in 125 patients with a history of acute coronary syndrome who had undergone detailed assessment of platelet function 30 days after the acute event. Using quantitative real-time polymerase chain reactions, 92 miRNAs were assessed in patients with acute coronary syndrome on different antiplatelet therapies. Key platelet-related miRNAs and YRNAs were correlated with platelet function tests. MiR-223 (rp=0.28; n=121; P=0.002), miR-126 (rp=0.22; n=121; P=0.016), and other abundant platelet miRNAs and YRNAs showed significant positive correlations with the vasodilator-stimulated phosphoprotein phosphorylation assay. YRNAs, miR-126, and miR-223 were also among the small RNAs showing the greatest dependency on platelets and strongly correlated with plasma levels of P-selectin, platelet factor 4, and platelet basic protein in the population-based Bruneck study (n=669). A single-nucleotide polymorphism that facilitates processing of pri-miR-126 to mature miR-126 accounted for a rise in circulating platelet activation markers. Inhibition of miR-126 in mice reduced platelet aggregation. MiR-126 directly and indirectly affects ADAM9 and P2Y12 receptor expression. CONCLUSIONS: Levels of platelet-related plasma miRNAs and YRNAs correlate with platelet function tests in patients with acute coronary syndrome and platelet activation markers in the general population. Alterations in miR-126 affect platelet reactivity.


Asunto(s)
Síndrome Coronario Agudo/sangre , Plaquetas/metabolismo , MicroARNs/sangre , Activación Plaquetaria , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/genética , Animales , Plaquetas/efectos de los fármacos , Línea Celular Tumoral , Perfilación de la Expresión Génica/métodos , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , Oligonucleótidos/genética , Oligonucleótidos/metabolismo , Activación Plaquetaria/efectos de los fármacos , Activación Plaquetaria/genética , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pruebas de Función Plaquetaria , Polimorfismo de Nucleótido Simple , Reacción en Cadena en Tiempo Real de la Polimerasa , Transfección
4.
Europace ; 20(3): e21-e29, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-28339860

RESUMEN

Aims: Dual-coil implantable cardioverter defibrillator (ICD) leads have traditionally been used over single-coil leads due to concerns regarding high defibrillation thresholds (DFT) and consequent poor shock efficacy. However, accumulating evidence suggests that this position may be unfounded and that dual-coil leads may also be associated with higher complication rates during lead extraction. This meta-analysis collates data comparing dual- and single-coil ICD leads. Methods and results: Electronic databases were systematically searched for randomized controlled trials (RCT) and non-randomized studies comparing single-coil and dual-coil leads. The mean differences in DFT and summary estimates of the odds-ratio (OR) for first-shock efficacy and the hazard-ratio (HR) for all-cause mortality were calculated using random effects models. Eighteen studies including a total of 138,124 patients were identified. Dual-coil leads were associated with a lower DFT compared to single coil leads (mean difference -0.83J; 95% confidence interval [CI] -1.39--0.27; P = 0.004). There was no difference in the first-shock success rate with dual-coil compared to single-coil leads (OR 0.74; 95%CI 0.45-1.21; P=0.22). There was a significantly lower risk of all-cause mortality associated with single-coil leads (HR 0.91; 95%CI 0.86-0.95; P < 0.0001). Conclusion: This meta-analysis suggests that single-coil leads have a marginally higher DFT but that this may be clinically insignificant as there appears to be no difference in first-shock efficacy when compared to dual-coil leads. The mortality benefit with single-coil leads most likely represents patient selection bias. Given the increased risk and complexity of extracting dual-coil leads, centres should strongly consider single-coil ICD leads as the lead of choice for routine new left-sided ICD implants.


Asunto(s)
Arritmias Cardíacas/terapia , Muerte Súbita Cardíaca/prevención & control , Desfibriladores Implantables , Cardioversión Eléctrica/instrumentación , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/mortalidad , Arritmias Cardíacas/fisiopatología , Muerte Súbita Cardíaca/epidemiología , Cardioversión Eléctrica/efectos adversos , Cardioversión Eléctrica/mortalidad , Diseño de Equipo , Humanos , Factores de Riesgo , Resultado del Tratamiento
5.
Clin Med (Lond) ; 14(4): 391-5, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25099841

RESUMEN

YouTube contains a large volume of medical educational material. This study assessed the quality of respiratory auscultation videos contained in YouTube. Videos were searched for using the terms 'breath sounds', 'respiratory sounds', 'respiratory auscultation' and/or 'lung sounds'. In total, 6,022 videos were located, 36 of which were considered suitable for scoring for video accuracy, comprehensiveness and quality. The average score was 3.32/6 (55.3% ± 1.30). Video score correlated with time-adjusted YouTube metadata: hits per day (0.496, p=0.002) and likes per day (0.534, p=0.001). Video score also correlated with the first search page on which the video was located in the 'breath sounds' and 'lung sounds' searches (-0.571, p=0.001; -0.445, p=0.014, respectively). The quality of videos was variable. Correlation between video score and some metadata values suggests that there is value for their use in judging video quality. However, the large number of videos found and inability to filter these results quickly makes locating educational content difficult.


Asunto(s)
Internet , Ruidos Respiratorios , Grabación en Video/normas , Humanos
6.
Artículo en Inglés | MEDLINE | ID: mdl-38752958

RESUMEN

BACKGROUND: Although the substrate in persistent atrial fibrillation (PeAF) is not limited to the pulmonary veins (PVs), PV isolation (PVI) remains the cornerstone ablation strategy. OBJECTIVES: The aim of this study was to describe the mechanism of outgoing wavefronts (WFs) originating in the PV sleeves during PeAF. METHODS: Eleven patients presenting for first-time PeAF ablation were recruited (mean age 63.1 ± 10.9 years, 91% men). A 64-electrode catheter (Constellation; 38 mm) was positioned within the PV under fluoroscopic guidance. An inverse mapping technique was used to reconstruct unipolar atrial electrograms on the PV surface, and the resulting phase maps were used to identify incoming and outgoing WFs at the PV junction and to classify focal and re-entrant activity within the PV sleeves. RESULTS: During PeAF, the PVs gave rise to outgoing WFs with a frequency of 3.7 s-1 (Q1-Q3: 3.4-5.4 s-1) compared with 3.6 s-1 (Q1-Q3: 2.8-4.2 s-1) for incoming WFs. Circuitous macroscopic re-entry was the dominant mechanism driving outgoing WFs (frequency of re-entry 2.7 s-1 [Q1-Q3: 2.0-3.3 s-1] compared with focal activity 1.4 s-1 [Q1-Q3: 1.1-1.5 s-1]; P < 0.006). This was initiated by incoming WFs in 80% of cases. Consecutive focal activation from the same location was infrequent (10.0% ± 6.6%, n = 10). Rotors ≥360° were never observed. The median ratio (R) of outgoing to incoming WF frequency was 1.14 (Q1-Q3: 0.84-1.75), with R > 1 in 6 of 11 PVs. CONCLUSIONS: Electric activity generated by PV sleeves during PeAF is due mainly to circuitous re-entry initiated by incoming waves, frequently with R > 1. That is, the PVs act less as drivers of atrial fibrillation than as "echo chambers" that sustain and amplify fibrillatory activity.

7.
Bioengineering (Basel) ; 10(11)2023 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-38002431

RESUMEN

BACKGROUND: Although electronic health records (EHR) provide useful insights into disease patterns and patient treatment optimisation, their reliance on unstructured data presents a difficulty. Echocardiography reports, which provide extensive pathology information for cardiovascular patients, are particularly challenging to extract and analyse, because of their narrative structure. Although natural language processing (NLP) has been utilised successfully in a variety of medical fields, it is not commonly used in echocardiography analysis. OBJECTIVES: To develop an NLP-based approach for extracting and categorising data from echocardiography reports by accurately converting continuous (e.g., LVOT VTI, AV VTI and TR Vmax) and discrete (e.g., regurgitation severity) outcomes in a semi-structured narrative format into a structured and categorised format, allowing for future research or clinical use. METHODS: 135,062 Trans-Thoracic Echocardiogram (TTE) reports were derived from 146967 baseline echocardiogram reports and split into three cohorts: Training and Validation (n = 1075), Test Dataset (n = 98) and Application Dataset (n = 133,889). The NLP system was developed and was iteratively refined using medical expert knowledge. The system was used to curate a moderate-fidelity database from extractions of 133,889 reports. A hold-out validation set of 98 reports was blindly annotated and extracted by two clinicians for comparison with the NLP extraction. Agreement, discrimination, accuracy and calibration of outcome measure extractions were evaluated. RESULTS: Continuous outcomes including LVOT VTI, AV VTI and TR Vmax exhibited perfect inter-rater reliability using intra-class correlation scores (ICC = 1.00, p < 0.05) alongside high R2 values, demonstrating an ideal alignment between the NLP system and clinicians. A good level (ICC = 0.75-0.9, p < 0.05) of inter-rater reliability was observed for outcomes such as LVOT Diam, Lateral MAPSE, Peak E Velocity, Lateral E' Velocity, PV Vmax, Sinuses of Valsalva and Ascending Aorta diameters. Furthermore, the accuracy rate for discrete outcome measures was 91.38% in the confusion matrix analysis, indicating effective performance. CONCLUSIONS: The NLP-based technique yielded good results when it came to extracting and categorising data from echocardiography reports. The system demonstrated a high degree of agreement and concordance with clinician extractions. This study contributes to the effective use of semi-structured data by providing a useful tool for converting semi-structured text to a structured echo report that can be used for data management. Additional validation and implementation in healthcare settings can improve data availability and support research and clinical decision-making.

8.
Interv Cardiol ; 18: e29, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38213747

RESUMEN

Background: Out-of-hospital cardiac arrest (OHCA) is associated with very poor clinical outcomes. An optimal pathway of care is yet to be defined, but prognostication is likely to assist in the challenging decision-making required for treatment of this high-risk patient cohort. The MIRACLE2 score provides a simple method of neuro-prognostication but as yet it has not been externally validated. The aim of this study was therefore to retrospectively apply the score to a cohort of OHCA patients to assess the predictive ability and accuracy in the identification of neurological outcome. Methods: Retrospective data of patients identified by hospital coding, over a period of 18 months, were collected from a large tertiary-level cardiac centre with a mature, multidisciplinary OHCA service. MIRACLE2 score performance was assessed against three existing OHCA prognostication scores. Results: Patients with all-comer OHCA, of presumed cardiac origin, with and without evidence of ST-elevation MI (43.4% versus 56.6%, respectively) were included. Regardless of presentation, the MIRACLE2 score performed well in neuro-prognostication, with a low MIRACLE2 score (≤2) providing a negative predictive value of 94% for poor neurological outcome at discharge, while a high score (≥5) had a positive predictive value of 95%. A high MIRACLE2 score performed well regardless of presenting ECG, with 91% of patients receiving early coronary angiography having a poor outcome. Conclusion: The MIRACLE2 score has good prognostic performance and is easily applicable to cardiac-origin OHCA presentation at the hospital front door. Prognostic scoring may assist decision-making regarding early angiographic assessment.

9.
JACC Cardiovasc Interv ; 16(19): 2439-2450, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37609699

RESUMEN

BACKGROUND: The MIRACLE2 score is the only risk score that does not incorporate and can be used for selection of therapies after out-of-hospital cardiac arrest (OHCA). OBJECTIVES: This study sought to compare the discrimination performance of the MIRACLE2 score, downtime, and current randomized controlled trial (RCT) recruitment criteria in predicting poor neurologic outcome after out-of-hospital cardiac arrest (OHCA). METHODS: We used the EUCAR (European Cardiac Arrest Registry), a retrospective cohort from 6 centers (May 2012-September 2022). The primary outcome was poor neurologic outcome on hospital discharge (cerebral performance category 3-5). RESULTS: A total of 1,259 patients (total downtime = 25 minutes; IQR: 15-36 minutes) were included in the study. Poor outcome occurred in 41.8% with downtime <30 minutes and in 79.3% for those with downtime >30 minutes. In a multivariable logistic regression analysis, MIRACLE2 had a stronger association with outcome (OR: 2.23; 95% CI: 1.98-2.51; P < 0.0001) than zero flow (OR: 1.07; 95% CI: 1.01-1.13; P = 0.013), low flow (OR: 1.04; 95% CI: 0.99-1.09; P = 0.054), and total downtime (OR: 0.99; 95% CI: 0.95-1.03; P = 0.52). MIRACLE2 had substantially superior discrimination for the primary endpoint (AUC: 0.877; 95% CI: 0.854-0.897) than zero flow (AUC: 0.610; 95% CI: 0.577-0.642), low flow (AUC: 0.725; 95% CI: 0.695-0.754), and total downtime (AUC: 0.732; 95% CI: 0.701-0.760). For those modeled for exclusion from study recruitment, the positive predictive value of MIRACLE2 ≥5 for poor outcome was significantly higher (0.92) than the CULPRIT-SHOCK (Culprit lesion only PCI Versus Multivessel PCI in Cardiogenic Shock) (0.80), EUROSHOCK (Testing the value of Novel Strategy and Its Cost Efficacy In Order to Improve the Poor Outcomes in Cardiogenic Shock) (0.74) and ECLS-SHOCK (Extra-corporeal life support in Cardiogenic shock) criteria (0.81) (P < 0.001). CONCLUSIONS: The MIRACLE2 score has superior prediction of outcome after OHCA than downtime and higher discrimination of poor outcome than the current RCT recruitment criteria. The potential for the MIRACLE2 score to improve the selection of OHCA patients should be evaluated formally in future RCTs.


Asunto(s)
Reanimación Cardiopulmonar , Paro Cardíaco Extrahospitalario , Humanos , Paro Cardíaco Extrahospitalario/diagnóstico , Paro Cardíaco Extrahospitalario/terapia , Resultado del Tratamiento , Choque Cardiogénico , Predicción
10.
Front Physiol ; 13: 873049, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35651876

RESUMEN

Introduction: Atrial fibrillation (AF) is the most prevalent cardiac dysrhythmia and percutaneous catheter ablation is widely used to treat it. Panoramic mapping with multi-electrode catheters can identify ablation targets in persistent AF, but is limited by poor contact and inadequate coverage. Objective: To investigate the accuracy of inverse mapping of endocardial surface potentials from electrograms sampled with noncontact basket catheters. Methods: Our group has developed a computationally efficient inverse 3D mapping technique using a meshless method that employs the Method of Fundamental Solutions (MFS). An in-silico test bed was used to compare ground-truth surface potentials with corresponding inverse maps reconstructed from noncontact potentials sampled with virtual catheters. Ground-truth surface potentials were derived from high-density clinical contact mapping data and computer models. Results: Solutions of the intracardiac potential inverse problem with the MFS are robust, fast and accurate. Endocardial surface potentials can be faithfully reconstructed from noncontact recordings in real-time if the geometry of cardiac surface and the location of electrodes relative to it are known. Larger catheters with appropriate electrode density are needed to resolve complex reentrant atrial rhythms. Conclusion: Real-time panoramic potential mapping is feasible with noncontact intracardiac catheters using the MFS. Significance: Accurate endocardial potential maps can be reconstructed in AF with appropriately designed noncontact multi-electrode catheters.

11.
Front Physiol ; 13: 873630, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35874529

RESUMEN

Atrial fibrillation (AF) is the most common cardiac dysrhythmia and percutaneous catheter ablation is widely used to treat it. Panoramic mapping with multi-electrode catheters has been used to identify ablation targets in persistent AF but is limited by poor contact and inadequate coverage of the left atrial cavity. In this paper, we investigate the accuracy with which atrial endocardial surface potentials can be reconstructed from electrograms recorded with non-contact catheters. An in-silico approach was employed in which "ground-truth" surface potentials from experimental contact mapping studies and computer models were compared with inverse potential maps constructed by sampling the corresponding intracardiac field using virtual basket catheters. We demonstrate that it is possible to 1) specify the mixed boundary conditions required for mesh-based formulations of the potential inverse problem fully, and 2) reconstruct accurate inverse potential maps from recordings made with appropriately designed catheters. Accuracy improved when catheter dimensions were increased but was relatively stable when the catheter occupied >30% of atrial cavity volume. Independent of this, the capacity of non-contact catheters to resolve the complex atrial potential fields seen in reentrant atrial arrhythmia depended on the spatial distribution of electrodes on the surface bounding the catheter. Finally, we have shown that reliable inverse potential mapping is possible in near real-time with meshless methods that use the Method of Fundamental Solutions.

12.
JACC Cardiovasc Interv ; 15(10): 1074-1084, 2022 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-35589238

RESUMEN

OBJECTIVES: The purpose of this study was to evaluate the impact of performing immediate coronary angiography (CAG) after out-of-hospital cardiac arrest (OHCA) with stratification of predicted neurologic injury and cardiogenic shock on arrival to a center. BACKGROUND: The role of immediate CAG for patients with OHCA is unclear, which may in part be explained by the majority of patients dying of hypoxic brain injury. METHODS: Between May 2012 and July 2020, patients from 5 European centers were included in the EUCAR (European Cardiac Arrest Registry). Patients were retrospectively classified into low vs high neurologic risk (MIRACLE2 score 0-3 vs ≥4) and degree of cardiogenic shock on arrival (Society for Cardiovascular Angiography and Interventions [SCAI] grade A vs B-E). A multivariable logistic regression analysis including immediate CAG was performed for the primary outcome of survival with good neurologic outcome (Cerebral Performance Category 1 or 2) at hospital discharge. RESULTS: Nine hundred twenty-six patients were included in the registry, with 405 (43.7%) in the low-risk group and 521 (56.3%) in the high-risk group. Immediate CAG was independently associated with improved survival with good neurologic outcome in the low MIRACLE2 risk group with ST-segment elevation myocardial infarction (OR: 11.80; 95% CI: 2.24-76.74; P = 0.048) and with SCAI grade B to E shock (OR: 3.23; 95% CI: 1.10-9.50; P = 0.031). No subgroups, including those with ST-segment elevation myocardial infarction and with SCAI grade B to E shock, achieved any benefit from early CAG in the high MIRACLE2 group. CONCLUSIONS: Combined classification of patients with OHCA with 12-lead electrocardiography, MIRACLE2 score 0 to 3, and SCAI grade B to E identifies a potential cohort of patients at low risk for neurologic injury who benefit most from immediate CAG.


Asunto(s)
Reanimación Cardiopulmonar , Paro Cardíaco Extrahospitalario , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Angiografía Coronaria , Humanos , Paro Cardíaco Extrahospitalario/diagnóstico por imagen , Paro Cardíaco Extrahospitalario/terapia , Estudios Retrospectivos , Choque Cardiogénico , Resultado del Tratamiento
13.
J Mol Cell Cardiol ; 50(1): 99-106, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20933519

RESUMEN

Hypertension is associated with heightened cardiac sympathetic drive whilst statins reduce angiotensin II (ATII) signalling, superoxide anion production and increase nitric oxide bioavailability, events that can potentially reduce peripheral cardiac sympathetic neurotransmission. We therefore investigated whether pravastatin alters peripheral cardiac sympathetic control in the spontaneously hypertensive rat (SHR). SHRs (16-18 weeks) had significantly (p<0.05) enhanced atrial (3)H-norepinephrine ((3)H-NE) release to field stimulation compared to normotensive WKYs. 2-week pravastatin supplementation significantly reduced (3)H-NE release to levels observed in the WKY. In-vivo, pravastatin lowered resting heart rate (HR) in the SHR despite not affecting arterial blood pressure or serum cholesterol. In SHR atria/right stellate ganglion preparations, the HR response to stellate stimulation (1, 3, and 5 Hz) was also significantly reduced by pravastatin whilst the HR response to exogenous NE (0.025-5 µmol) remained similar. The nitric oxide synthase (NOS) inhibitor l-NAME (1 mmol/l) increased (3)H-NE release by similar amounts in atria from supplemented and non-supplemented SHRs, whilst Western blotting showed no difference in protein levels of nNOS, eNOS, guanylyl cyclase, or the NADPH oxidase subunits Gp91 and P40 phox. Pravastatin significantly reduced cardiac ATII levels and angiotensin converting enzyme 1 and 2 expressions whilst protein levels of the ATII receptor (ATR(1)) remained unchanged in the SHR. Immunohistochemistry co-localised ATR(1) with tyrosine hydroxylase positive neurons in the stellate ganglion. The ATR(1) antagonist Losartan (5 µmol) equalised release of (3)H-NE to comparable levels in supplemented and non-supplemented SHRs. These results suggest 2-week pravastatin treatment reduces cardiac ATII, and prevents its facilitatory effect on NE release thus normalising cardiac sympathetic hyper-responsiveness in SHRs.


Asunto(s)
Pravastatina/farmacología , Animales , Western Blotting , Colesterol/metabolismo , Guanilato Ciclasa/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Inmunohistoquímica , Losartán/farmacología , Masculino , NADPH Oxidasas/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo I/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Peptidil-Dipeptidasa A/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptores de Angiotensina/metabolismo , Tirosina 3-Monooxigenasa/metabolismo
14.
Eur Heart J Case Rep ; 5(2): ytaa548, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33598621

RESUMEN

BACKGROUND: The Gerbode defect is a rare abnormal communication between the left ventricle (LV) and right atrium (RA). The lesion is either congenital or acquired. Acquired defects are largely iatrogenic or infective in origin. We present two cases of acquired Gerbode defects with similar clinical presentations but very different outcomes. CASE SUMMARIES: Patient 1 A 64-year-old male presented with features of decompensated cardiac failure and a low-grade temperature. Dehiscence of a recently implanted bioprosthetic aortic valve and high-velocity LV to RA jet (Gerbode defect) was found on echocardiography. Blood cultures grew Staphylococcus warneri and the diagnosis of infective endocarditis was established. The patient was treated with intravenous antibiotics and the aortic valve and Gerbode defect were successfully surgically repaired.Patient 2 An 81-year-old male presented after being found on the floor at home. On admission, he was clinically septic with evidence of decompensated heart failure. No clear infective focus was initially found. Transthoracic echocardiography revealed severe left ventricular impairment, with a normal bioprosthetic aortic valve. He was treated with intravenous antibiotics, but later deteriorated with evidence of embolic phenomena. Repeat echocardiography revealed a complex infective aortic root lesion with bioprosthetic valve dehiscence and flow demonstrated from the LV to RA. Unfortunately, the patient succumbed to the infection and cardiac complications. DISCUSSION: The Gerbode defect is a rare but important complication of infective endocarditis and valve surgery. Care needs to be taken to assess for Gerbode defect shunts on echocardiogram, especially in the context of previous cardiac surgery.

15.
Cardiol J ; 28(1): 129-135, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-31225635

RESUMEN

BACKGROUND: ST2 is a circulating biomarker that is well established for predicting outcome in heart failure (HF). This is the first study to look at ST2 concentrations in optimally treated patients with stable but significant left ventricular systolic dysfunction (LVSD) compared to patients with severe aortic stenosis (AS). METHODS: Two cohorts were retrospectively studied: 94 patients undergoing transcatheter aortic valve implantation for severe AS (63 with normal ejection fraction [EF] and 31 with reduced EF), and 50 patients with severe LVSD from non-valvular causes. ST2 pre-procedural samples were taken, and repeated again at 3 and 6 months. Patients were followed-up for 2 years. Data was analyzed using SPSS software. RESULTS: Baseline concentrations of soluble ST2 did not differ significantly between the HF group and AS group with normal EF (EF ≥ 50%). However, in the AS group with a low EF (EF < 50%) ST2 concentrations were significantly higher that the HF group (p = 0.009). New York Heart Association class IV HF, baseline N-terminal pro-B-type natriuretic peptide and gender were all independent predictors of soluble ST2 (sST2) baseline concentrations. CONCLUSIONS: Raised ST2 concentrations in the context of severe AS may be a marker for subclinical or clinical left ventricular dysfunction. More research is required to assess its use for assessment of prognosis and response to treatment.


Asunto(s)
Estenosis de la Válvula Aórtica , Insuficiencia Cardíaca , Reemplazo de la Válvula Aórtica Transcatéter , Disfunción Ventricular Izquierda , Estenosis de la Válvula Aórtica/cirugía , Biomarcadores , Humanos , Péptido Natriurético Encefálico/química , Péptido Natriurético Encefálico/metabolismo , Estudios Retrospectivos , Volumen Sistólico/fisiología
16.
J Am Soc Echocardiogr ; 33(12): 1509-1516, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33051107

RESUMEN

BACKGROUND: Life-threatening arrhythmias (LTAs) can trigger sudden cardiac death or provoke implantable cardioverter-defibrillator (ICD) discharges that escalate morbidity and mortality. Longitudinal myofibrils predominate in the subendocardium, which is uniquely sensitive to arrhythmogenic triggers. In this study, we test the hypothesis that mitral annular systolic velocity (S'), a simple routinely obtained tissue Doppler index of LV long-axis systolic function, might predict lethal arrhythmias irrespective of left ventricular ejection fraction (LVEF). METHODS: This is a retrospective analysis of data from 302 patients (mean age, 68 years; LVEF, 32%; 77% male; 52% ischemic; 35% primary prevention; and 53% cardiac resynchronization therapy defibrillator [CRT-D]) who were followed up (median, 15 months) at two centers after receipt of an ICD or CRT-D for diverse indications. S', averaged from tissue Doppler-derived medial and lateral mitral annular velocities, was correlated with the primary outcome of time to sustained ventricular tachycardia (VT) or fibrillation (VF) needing device therapy. RESULTS: The median S' was 5.1 (interquartile range, 4.0-6.2) cm/sec and lower in CRT-D than ICD subjects (4.5 [3.8-5.6] cm/sec vs 5.5 [4.8-6.8] cm/sec, P < .001). Fifty-six (19%) subjects had LTA. Each 1 cm/sec higher S' correlated to a 30% decreased risk of LTA (hazard ratio = 0.70; 95% CI, 0.57-0.87; P = .001) independently of age, sex, ß-blocker use, center, ICD use, and LVEF. Adding S' to the baseline Cox model improved net reclassification (P = .02). An S' > 5.6 cm/sec was the best cutoff and linked to a 58% lower LTA risk than an S' ≤ 5.6 cm/sec (95% CI, 0.23-0.85; P = .02). CONCLUSIONS: A higher S' is associated with a reduced probability of LTA in cardiac device recipients irrespective of LVEF and may have the potential to be used clinically to titrate medical, device, and ablative therapies to mitigate future arrhythmic risk.


Asunto(s)
Desfibriladores Implantables , Taquicardia Ventricular , Anciano , Muerte Súbita Cardíaca , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular Izquierda
17.
BMJ Case Rep ; 20182018 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-29844036

RESUMEN

An 83-year-old woman, with a background of treated squamous cell oesophageal cancer, presented with a 3-week history of stridor. Of note, the patient had no risk factors for oesophageal cancer other than age. Clinical examination was unremarkable apart from stridor. Laboratory investigations, including arterial blood gas on room air, were unremarkable. Radiological examination revealed a 4.5×3.5×3.6 cm mass involving the posterior trachea and invading the tracheal orifice. Oesophagogastroduodenoscopy and rigid bronchoscopy confirmed an extensive tumour arising from the lower oesophagus and invading the trachea, causing 90% airway obstruction for a 6 mm length ending 1.5 cm above the carina. Biopsy revealed a poorly differentiated carcinoma with foci of squamous cell carcinoma. Unfortunately, the patient passed away 2 months after palliative tracheal stent placement.


Asunto(s)
Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Neoplasias de la Tráquea/diagnóstico , Anciano de 80 o más Años , Broncoscopía , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/cirugía , Diagnóstico Diferencial , Neoplasias Esofágicas/patología , Resultado Fatal , Femenino , Humanos , Ruidos Respiratorios/etiología , Stents , Tomografía Computarizada por Rayos X , Neoplasias de la Tráquea/diagnóstico por imagen , Neoplasias de la Tráquea/secundario , Neoplasias de la Tráquea/cirugía
18.
Ir J Med Sci ; 187(4): 1089-1096, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29541933

RESUMEN

BACKGROUND: Hypertensive urgency is defined as a severely elevated systolic blood pressure (SBP) of ≥ 180 mmHg and/or diastolic blood pressure (DBP) of ≥ 120 mmHg, in the absence of end organ damage. It is known that there are racial differences in prevalence and severity of hypertension but there is a dearth of studies looking at hypertensive urgency in Black populations living in Europe. AIMS: We sought to define the clinical characteristics of Black patients presenting with hypertensive urgency, in order to better define the risks and complications this growing population of patients faces. METHODS: This was a single-centre retrospective cohort study of 63 consecutive Black and Afro-Caribbean patients attending a South London district general hospital outpatient hypertension clinic from April 2014 to June 2016. All patients had initially presented with hypertensive urgency to their GP, the Emergency Department, or the hospital's medical take. RESULTS: The cohort had a mean age of 52.7 years and an even gender balance. Thirty-four patients had a pre-existing diagnosis of hypertension, with a 9-year median time since diagnosis. This was the first presentation of hypertension for the remaining 46%. Other comorbidities found were diabetes mellitus (10%), ischaemic heart disease (5%), hyperlipidaemia (5%), and cerebrovascular disease (2%). Patients who drank alcohol regularly were found to have significantly higher blood pressures than those who did not. Most patients presented with typical symptoms of uncontrolled hypertension, with headache (25%) and chest pain (16%) being most common. Features of end organ damage were also common, with 32 patients having hypertensive retinopathy, 16 patients having proteinuria and 14 patients found to have left ventricular hypertrophy on echocardiography. CONCLUSION: The large proportion of newly diagnosed hypertensive patients presenting with end organ signs of prolonged uncontrolled hypertension suggests that there are significant numbers of undiagnosed Black patients in the community, suggesting that we should more actively conduct test for hypertension and its complications when we encounter these patients, who constitute a growing part of the populations in Europe.


Asunto(s)
Población Negra/etnología , Presión Sanguínea/fisiología , Hipertensión/etnología , Adulto , Diabetes Mellitus/etnología , Ecocardiografía , Servicio de Urgencia en Hospital , Europa (Continente) , Femenino , Humanos , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/complicaciones , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos
19.
J Interv Card Electrophysiol ; 49(2): 181-189, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28386821

RESUMEN

PURPOSE: Patients at high non-sudden cardiac death risk may gain no significant benefit from implantable cardioverter-defibrillator (ICD) therapy. A number of approaches have been proposed to identify these patients, including single clinical markers and more complex scoring systems. The aims of this study were to use the proposed scoring systems to (1) establish how many current ICD recipients may be too high risk to derive significant benefit from ICD therapy and (2) evaluate how well the scoring systems predict short-term mortality in an unselected ICD cohort. METHODS: We performed a single-centre retrospective observational study of all new ICD implants over 5 years (2009-2013). We used four published scoring systems (Bilchick, Goldenberg, Kramer and Parkash) and serum urea to identify new ICD recipients whose short-term predicted mortality risk was high. We evaluated how well the scoring systems predicted death. RESULTS: Over 5 years, there were 406 new implants (79% male, mean age 70 (60-76), 58% primary prevention). During a follow-up of 936 ± 560 days, 96 patients died. Using the scoring systems, the proportion of ICD recipients predicted to be at high short-term mortality risk were 5.9% (Bilchick), 34.7% (Goldenberg), 7.4% (Kramer), 21.4% (Parkash) and 25% (urea, cut-off of >9.28 mM). All four risk scores predicted mortality (P < 0.0001); however, none outperformed urea for the prediction of 1- or 3-year mortality. CONCLUSIONS: Using published scoring systems, a significant proportion of current ICD recipients are at high short-term mortality risk. Although all four scoring systems predicted mortality during follow-up, none significantly outperformed serum urea.


Asunto(s)
Muerte Súbita Cardíaca/prevención & control , Desfibriladores Implantables , Selección de Paciente , Prevención Primaria , Medición de Riesgo , Anciano , Biomarcadores , Femenino , Humanos , Londres , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo
20.
BMJ Case Rep ; 20162016 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-27122103

RESUMEN

Re-expansion pulmonary oedema (REPO) is a rare complication of pleural fluid thoracocentesis and has been associated with a high mortality rate. There is limited evidence to inform on its most effective management. We present two cases of large volume thoracocentesis resulting in acute respiratory decompensation that was treated by reintroducing the drained pleural fluid back into the pleural cavity. We also present a review of the literature specifically assessing the reported incidence rate of REPO after pleural fluid drainage. In both of our cases, symptoms and signs of respiratory instability were promptly reversed on reintroduction of the drained pleural fluid into the patient's pleural space-a therapy we have termed 'rapid pleural space re-expansion'. This was not associated with any short-term adverse outcomes. The occurrence of REPO is a rare event with most cohort studies reporting an incidence of between 0% and 1%.


Asunto(s)
Drenaje/efectos adversos , Disnea/etiología , Cavidad Pleural , Derrame Pleural , Atelectasia Pulmonar/terapia , Edema Pulmonar/terapia , Toracocentesis/efectos adversos , Anciano , Disnea/terapia , Femenino , Humanos , Incidencia , Derrame Pleural/terapia , Neumotórax/terapia , Atelectasia Pulmonar/etiología , Edema Pulmonar/epidemiología , Edema Pulmonar/etiología
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