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Artigo em Inglês | MEDLINE | ID: mdl-30878439


OBJECTIVES: This study used optical coherence tomography to investigate the mechanism of false lumen (FL) formation in spontaneous coronary artery dissection (SCAD) by studying: 1) differences between fenestrated and nonfenestrated SCAD; 2) vasa vasorum density; and 3) light attenuation characteristics of the FL. BACKGROUND: SCAD is an increasingly recognized cause of acute coronary syndromes, characterized by FL formation and compression of the true lumen (TL). The mechanisms underlying FL formation remain poorly understood. METHODS: A total of 65 SCAD patients (68 vessels) who underwent acute OCT imaging as part of routine clinical care were included. Images were classified by the absence or presence of a connection (fenestration) between the TL and FL. Indexed measurements of TL stenosis, external elastic lamina (EEL) area, FL area, and light attenuation of the FL were assessed. Vasa vasorum densities of SCAD cases were compared with those in control non-SCAD myocardial infarction cases. RESULTS: In nonfenestrated cases, there was significantly larger expansion of the EEL area (9.1% vs. -1.9%; p <0.05) and a larger FL area (73.6% vs. 53.2%, respectively; p <0.05) in dissected segments. No significant differences were found between vasa vasorum density in SCAD and those in control subjects. The FL contents were heterogeneous but attenuated less light than whole blood or thrombus (4.28 ± 0.55 mm-1 vs. 5.08 ± 0.56 mm-1; p < 0.05; vs. 4.96 ± 0.56 mm-1; p < 0.05). CONCLUSIONS: These observational data suggest that the absence of a fenestration leads to increased FL pressure and compression of the TL. Although vasa vasorum may still be implicated in pathogenesis, increased vasa vasorum density could be an epiphenomenon of vascular healing.

J Am Coll Cardiol ; 73(1): 58-66, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621952


BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. OBJECTIVES: This study sought to test the association between the rs9349379 genotype and SCAD. METHODS: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. RESULTS: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. CONCLUSIONS: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD.

Heart Lung Circ ; 25(12): 1210-1217, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27396244


BACKGROUND: Despite advances in cardiopulmonary resuscitation, functional survival remains low after out-of-hospital cardiac arrest (OOHCA). Intra-aortic balloon pump (IABP) therapy has recently been shown to augment cerebral blood flow. Whether IABP therapy in the post-resuscitation period improves functional outcomes is unknown. METHODS: We analysed 174 consecutive patients who were successfully resuscitated from an OOHCA between 2011-2013 at Harefield Hospital, London. We analysed functional status at discharge and mortality up to one year. RESULTS: A total of 55 patients (32.1%) received IABP therapy. Comparing those receiving IABP with those not receiving IABP, there was no difference in favourable functional status at discharge (49.1% vs. 57.1%, p=0.321); and mortality at one year (45.5% vs. 35.5%, p=0.164). Multivariable analyses identified IABP therapy as a strong independent predictor for favourable functional status at discharge (OR=7.51, 95% CI: 2.15-26.14, p=0.002) and this association was maintained in propensity-score adjusted analyses (OR=9.90, 95% CI: 2.11-46.33, p=0.004) and inverse probability treatment weighted analyses (OR=10.84, 95% CI: 2.75-42.69, p<0.001). However, IABP therapy was not an independent predictor for mortality at one year (HR=0.93, 95% CI: 0.52-1.65, p=0.810) and this was confirmed in both propensity-score adjusted and inverse probability treatment weighted analyses. CONCLUSIONS: In this observational analysis of patients surviving an OOHCA, the use of IABP therapy in the post-resuscitation period was associated with improved functional outcomes. This warrants further evaluation in larger prospective studies.

Balão Intra-Aórtico , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/cirurgia , Período Pós-Operatório , Ressuscitação/métodos , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ressuscitação/efeitos adversos , Taxa de Sobrevida
Am J Cardiol ; 115(6): 730-7, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25644852


Despite advances in cardiopulmonary resuscitation (CPR), survival remains low after out-of-hospital cardiac arrest (OOHCA). Acute coronary ischemia is the predominating precipitant, and prompt delivery of patients to dedicated facilities may improve outcomes. Since 2011, all patients experiencing OOHCA in London, where a cardiac etiology is suspected, are systematically brought to heart attack centers (HACs). We determined the predictors for survival and favorable functional outcomes in this setting. We analyzed 174 consecutive patients experiencing OOHCA from 2011 to 2013 brought to Harefield Hospital-a designated HAC in London. We analyzed (1) all-cause mortality and (2) functional status using a modified Rankin scale (mRS 0 to 6, where mRS0-3(+) = favorable functional status). The overall survival rates were 66.7% (30 days) and 62.1% (1 year); and 54.5% had mRS0-3(+) at discharge. Patients with mRS0-3(+) had reduced mortality compared to mRS0-3(-): 30 days (1.2% vs 72.2%, p <0.001) and 1 year (5.3% vs 77.2%, p <0.001). Multivariate analyses identified lower patient comorbidity, absence of cardiogenic shock, bystander CPR, ventricular tachycardia/ventricullar fibrillation as initial rhythm, shorter duration of resuscitation, prehospital advanced airway, absence of adrenaline and inotrope use, and intra-aortic balloon pump use as predictors of mRS0-3(+). Consistent predictors of increased mortality were the presence of cardiogenic shock, advanced airway use, increased duration of resuscitation, and absence of therapeutic hypothermia. A streamlined delivery of patients experiencing OOHCA to dedicated facilities is associated with improved functional status and survival. Our study supports the standardization of care for such patients with the widespread adoption of HACs.

Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/terapia , Idoso , Epinefrina/administração & dosagem , Feminino , Hospitais Universitários , Humanos , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/etiologia , Parada Cardíaca Extra-Hospitalar/fisiopatologia , Alta do Paciente , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Choque Cardiogênico/mortalidade , Padrão de Cuidado , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Reino Unido/epidemiologia
PLoS One ; 9(8): e102645, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25115870


The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.

Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Variação Genética , Genoma Humano , Alelos , Ásia , Genética Populacional , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA
Acute Med ; 8(3): 114-6, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-21603662


We present the case of a 40-year old female who was initially seen by her GP and the Emergency Department with pneumonia failing to respond to oral antibiotics. Her severity assessment score categorised her as being in a low risk group and she was discharged. Subsequent admission and further investigations diagnosed Human Immunodeficiency Virus infection and Pneumocystis jeruvici pneumonia. It is important for emergency departments and acute physicians to apply risk validation tools appropriately and to be alert to underlying immunosuppression.