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1.
Circulation ; 142(11): 1092-1105, 2020 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-32697107

RESUMEN

BACKGROUND: Aortic valve stenosis is an increasingly prevalent degenerative and inflammatory disease. Transcatheter aortic valve implantation (TAVI) has revolutionized its treatment, thereby avoiding its life-threatening/disabling consequences. Whether aortic valve stenosis is accelerated by inflammation and whether it is itself a cause of inflammation are unclear. We hypothesized that the large shear forces exerted on circulating cells, particularly on the largest circulating cells, monocytes, while passing through stenotic aortic valves result in proinflammatory effects that are resolved with TAVI. METHODS: TAVI provides a unique opportunity to compare the activation status of monocytes under high shear stress (before TAVI) and under low shear stress (after TAVI). The activation status of monocytes was determined with a single-chain antibody, MAN-1, which is specific for the activated ß2-integrin Mac-1. Monocyte function was further characterized by the adhesion of myocytes to stimulated endothelial cells, phagocytic activity, uptake of oxidized low-density lipoprotein, and cytokine expression. In addition, we designed a microfluidic system to recapitulate the shear rate conditions before and after TAVI. We used this tool in combination with functional assays, Ca2+ imaging, siRNA gene silencing, and pharmacological agonists and antagonists to identify the key mechanoreceptor mediating the shear stress sensitivity of monocytes. Last, we stained for monocytes in explanted stenotic aortic human valves. RESULTS: The resolution of high shear stress through TAVI reduces Mac-1 activation, cellular adhesion, phagocytosis, oxidized low-density lipoprotein uptake, and expression of inflammatory markers in monocytes and plasma. Using microfluidics and pharmacological and genetic studies, we could recapitulate high shear stress effects on isolated human monocytes under highly controlled conditions, showing that shear stress-dependent calcium influx and monocyte adhesion are mediated by the mechanosensitive ion channel Piezo-1. We also demonstrate that the expression of this receptor is shear stress dependent and downregulated in patients receiving TAVI. Last, we show monocyte accumulation at the aortic side of leaflets of explanted aortic valves. CONCLUSIONS: We demonstrate that high shear stress, as present in patients with aortic valve stenosis, activates multiple monocyte functions, and we identify Piezo-1 as the mainly responsible mechanoreceptor, representing a potentially druggable target. We demonstrate an anti-inflammatory effect and therefore a novel therapeutic benefit of TAVI.


Asunto(s)
Antiinflamatorios/administración & dosificación , Estenosis de la Válvula Aórtica , Canales Iónicos/sangre , Monocitos/metabolismo , Resistencia al Corte , Estrés Mecánico , Reemplazo de la Válvula Aórtica Transcatéter , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/sangre , Estenosis de la Válvula Aórtica/cirugía , Femenino , Humanos , Masculino
2.
Am J Cardiol ; 124(7): 1085-1090, 2019 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-31353006

RESUMEN

Limited data exist regarding transcatheter aortic valve implantation (TAVI) in nonagenarians. This study evaluates the short- and mid-term outcomes of nonagenarians after TAVI. Between 2008 and 2017, all patients who underwent TAVI in 2 centers in Australia were prospectively included in a registry and followed-up for 5 years. Outcomes were based on VARC-2 criteria. Additionally, the patient's reliance on daily living support at 1 year was evaluated. Of the 588 patients, 71 (12.1%) were ≥90 years old (mean age 92.2 ± 2 vs 83.2 ± 6 years in <90-year-old patients), with a median STS-PROM score of 5.7 (vs 3.9 in <90-year-old patients, odds ratio [OR] 1.07, 95% confidence interval 1.01 to 1.13, p = 0.02) and a median clinical frailty score of 4 (vs 4 <90-year-old patients, OR 0.88, p = 0.44). Mortality was 0% in ≥90-year-old patients at 30 days (vs 1.4% in <90-year-old patients; p = 0.82) and 12% at 1 year (vs 7.4%, in <90-year-old patients; hazard ratio 1.64, p = 0.20). There were no significant differences in periprocedural complications and mortality at 5 years between the 2 groups. At 1 year, nonagenarians were significantly more likely to live in an aged-care facility compared with <90-year-old patients (25% vs 16%, OR 5.99, 95% confidence interval 2.62 to 13.67, p <0.001). In conclusion, carefully selected nonagenarians have excellent short- and mid-term outcomes post-TAVI and should therefore not be refused based on age alone. Nevertheless, the significantly higher rate of transfer to an aged-care facility highlights the importance of a more refined frailty assessment before TAVI than the currently widely used clinical frailty score.


Asunto(s)
Estenosis de la Válvula Aórtica/mortalidad , Estenosis de la Válvula Aórtica/cirugía , Complicaciones Posoperatorias/epidemiología , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Factores de Edad , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/complicaciones , Australia , Estudios de Cohortes , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Selección de Paciente , Tasa de Supervivencia , Reemplazo de la Válvula Aórtica Transcatéter/instrumentación , Resultado del Tratamiento
3.
World J Methodol ; 9(1): 1-19, 2019 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-30705870

RESUMEN

Coronary artery disease (CAD) screening and diagnosis are core cardiac specialty services. From symptoms, autopsy correlations supported reductions in coronary blood flow and dynamic epicardial and microcirculatory coronaries artery disease as etiologies. While angina remains a clinical diagnosis, most cases require correlation with a diagnostic modality. At the onset of the evidence building process much research, now factored into guidelines were conducted among population and demographics that were homogenous and often prior to newer technologies being available. Today we see a more diverse multi-ethnic population whose characteristics and risks may not consistently match the populations from which guideline evidence is derived. While it would seem very unlikely that for the majority, scientific arguments against guidelines would differ, however from a translational perspective, there will be populations who differ and importantly there are cost-efficacy questions, e.g., the most suitable first-line tests or what parameters equate to an adequate test. This article reviews non-invasive diagnosis of CAD within the context of multi-ethnic patient populations.

4.
J Cardiovasc Thorac Res ; 8(1): 46-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27069568

RESUMEN

Pseudoaneurysm of aorta is a rare condition usually seen after aortic surgeries or serious accidents. Here we report a 60 years old man without any previous medical condition who presented with non-specific symptoms and underwent different investigations for more than 1 year, until the presence of a continuous murmur raised suspicion toward his cardiovascular system. In echocardiographic and computed tomography (CT) angiographic studies a large pseudoaneurysm of aortic arch with compression effect on pulmonary artery was detected. At this stage he remembered having suffered a minor trauma 10 years ago. He finally underwent operation and his aortic wall was repaired successfully with a patch. This case highlights the importance of thorough history taking and physical examination in patients irrespective of symptoms and high index of suspicion to detect this life-threatening condition.

5.
J Cardiol Cases ; 10(6): 205-207, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30534244

RESUMEN

Congenital coronary anomalies are mostly asymptomatic, detected accidentally during invasive or non-invasive imaging. One of the least encountered of such anomalies is single coronary ostium. Considering the fact that the whole myocardium is perfused by a single coronary vessel, performing percutaneous coronary stenting is a challenge for interventional cardiologists with some authors even considering it as a contraindication. Here we present a rare case of single coronary artery as a result of terminal extension of right coronary artery from left circumflex artery, for whom successful balloon angioplasty and stenting of left anterior descending artery after myocardial infarction was done. .

6.
J Cardiovasc Dis Res ; 1(1): 27-8, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21188087

RESUMEN

BACKGROUND: #ENTITYSTARTX02014; The Yellow Oleander is an ornamental tree that is common throughout the tropics. Ingestion of its seeds results in a clinical picture similar to digoxin toxicity. OBJECTIVES: #ENTITYSTARTX02014; The aim of this study was to evaluate cardiac findings in acute Yellow Oleander poisoning. METHODS AND MATERIALS: #ENTITYSTARTX02014; A total of 21 patients with history of Yellow Oleander ingestion were enrolled in this study. RESULTS: #ENTITYSTARTX02014; All symptomatic patients had conduction defects affecting the sinus node, theatrio-ventricular node or both. Patients showing cardiac arrhythmias that required specific management had significantly higher serum potassium concentrations. CONCLUSION: #ENTITYSTARTX02014; Most of the symptomatic patients had conduction defects affecting sinus or atrio-ventricular nodes but few had atrial or ventricular arrhythmias typical of digoxin poisoning.

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