A Common Variant at the 3'untranslated Region of the CCL7 Gene (rs17735770) Is Associated With Decreased Susceptibility to Coronary Heart Disease.

Monocytes participate in the development of atherosclerosis through the action of cytokines and other inflammatory mediators. Among them, CCR2 and its ligands, CCL2 and CCL7 play an important role, so the main objective of this work was to determine whether genetic variants affecting their activity were associated with cardiovascular disease. A cohort of 519 patients that have suffered coronary events was analyzed under a propensity score-matching protocol selecting a homogeneous set of cases and controls, according to age, sex, smoking status, dyslipidemia, arterial hypertension and type 2 diabetes as risk factors. While dyslipidemia and arterial hypertension were more prevalent among patients with angina pectoris, current smoking status and elevated inflammatory markers, including total leukocyte and monocyte counts, were more likely associated with acute coronary events. Propensity score matching analysis, performed to eliminate the influence of these risk factors and highlight genetic modifiers, revealed that a single nucleotide variant, rs17735770 at the 3'untranslated region of the CCL7 gene transcript, was associated with decreased cardiovascular risk in a group represented mostly by men, with an average age of 57, and without significant differences in traditional risk factors. Furthermore, the presence of this variant altered the local mRNA structure encompassing a binding site for miR-23ab, resulting in increased translation of a reporter gene in a miR23 independent fashion. The rs17735770 genetic variant led to increased expression of CCL7, a potential antagonist of CCR2 at inflammatory sites, where it could play a meaningful role during the evolution of atherosclerosis.

Blood test assessment of liver ultrasound findings in patients with Fontan surgery.

Hepatic complications are common in patients with Fontan surgery. The objective of this observational study is to compare demographic, clinical and blood test data in patients older than 14 years old with a Fontan procedure (cases) and asymptomatic patients with single non-operated restrictive ventricular septal defect (VSD) (controls) and to determine whether there are differences in blood collection and liver disease scores according to the liver ultrasound findings in the group of Fontan patients. The liver findings were classified as mild (normal or heterogeneous echogenicity) and significant (nodular surface, small hyperechoic nodules or hepatocarcinoma). 74 patients (14 patients with a Fontan procedure and 60 patients with a restrictive VSD) were included in the study. Median age was 18 (14-45) years old and 41 patients were males. Fontan patients had significantly lower platelet count, lower mean platelet volume (MPV) and lower glucose levels than patients with single non-operated restrictive VSD. On the contrary, Fontan patients showed higher liver enzymes [aspartate aminotransferase (AST) and alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT)], N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and thyroid-stimulating hormone (TSH) concentrations than patients with restrictive VSD. 4 out of 14 (29%) patients with Fontan operation and significant liver ultrasound findings showed greater number of cardiac surgeries, lower MPV values and higher GGT and TSH levels than Fontan patients with mild findings. In conclusion, Fontan patients showed higher liver enzymes (AST, ALT and GGT) than controls and Fontan patients with significant liver ultrasound findings had higher GGT and TSH concentrations than Fontan patients with mild findings.

Vitreous inflammation and macular edema secondary to perfluoro-n-octane toxicity.

Although it is not frequent, residual perfluoro-n-octane elicits an inflammatory response in form of macroscopic white flake-like material on intraocular structures formed by macrophages with intracellular vacuoles containing it. Macular edema could be another manifestation of this entity which, to our knowledge, has not been described so far. We describe an unusual case of intravitreal inflammation and macular edema secondary to the presence of residual perfluoro-n-octane after a surgical intervention of retinal detachment.

Multimodal imaging in choroidal metastasis from primary adenocarcinoma of the esophagus: a case report.

Adenocarcinoma of the esophagus is an extremely rare cause of choroidal metastasis. We report a case of a 53-year-old male with a six-month history of weight loss and two months of solid dysphagia, who presented with acute vision loss of his right eye, of 2 days of evolution. Ophthalmologic examination revealed bilateral choroidal masses associated with exudative retinal detachment in the right eye. Gastroduodenoscopy revealed a mass in the distal esophagus and endoscopic biopsy evidenced esophageal adenocarcinoma. The systemic study disclosed multiple pulmonary and liver metastatic nodules and enlarged thorax and abdomen lymph nodes. Systemic palliative chemotherapy was started, and specific ophthalmological treatment was ruled out given the patient's situation. Choroidal metastasis of esophageal adenocarcinoma is a very rare cause of metastasis and there are very few cases reported until present in literature.

Anterior spinal artery syndrome and aortic dissection.

BACKGROUND: Anterior spinal artery syndrome, usually resulting in flaccid paraplegia, is a rare but disastrous complication that can occur after surgery of aortic aneurysms and aortic dissections. Spinal cord infarct as the initial clinical presentation of aortic dissection is a very rare finding. CASE REPORT: A 42-year-old male patient who comes to the emergency department due to severe chest pain associated with presyncope and paraplegia of the lower limbs in the context of type A aortic dissection. CONCLUSIONS: Recognizing this atypical clinical presentation of aortic dissection and knowing how to approach it is critical for an early diagnosis and to minimize the risk of spinal cord ischemia during surgery.

ANTECEDENTES: La lesión de la médula espinal, generalmente resultante en paraplejia flácida, es una complicación rara, pero desastrosa, que puede ocurrir tras intervenciones quirúrgicas de aneurismas o disecciones de aorta. La presentación clínica inicial de una disección de aorta como un síndrome de la arteria espinal anterior es un hallazgo muy infrecuente. CASO CLÍNICO: Varón de 42 años que acude al servicio de urgencias hospitalario por dolor torácico intenso asociado a cuadro presincopal y paraplejia de miembros inferiores en el contexto de una disección de aorta tipo A. CONCLUSIONES: Reconocer esta forma de presentación clínica y saber cómo realizar un abordaje adecuado es fundamental para el diagnóstico precoz y para minimizar el riesgo quirúrgico de presentar isquemia medular.

Cardiovascular risk factors and arterial thrombotic events in congenital heart disease patients.

INTRODUCTION: As congenital patients get older, it can be hypothesised that cardiovascular risk factors increase. METHODS: Retrospective study of congenital heart disease (CHD) patients attended between January 2008 and September 2018. Cardiovascular risk factors, myocardial infarction, stroke, peripheral vascular disease, and analytical data such as serum glucose and lipid profile were determined. RESULTS: Eight hundred and eighteen CHD patients and 1955 control patients matched for age and sex were studied. CHD patients were distributed in simple (462 patients), moderate (228 patients) and great (128 patients) complexity. Median age in CHD patients was 33 (25-41) years old and 56% were male. CHD patients were significantly more hypertensive and diabetic but less dyslipidemic and smokers than patients in the control group. Twenty-seven (3.3%) CHD patients had an arterial thrombotic event: 3 coronary, 22 neurological and 2 peripheral vascular disease. No significant differences were seen in the incidence of myocardial infarction between the control and the CHD groups. However CHD patients had a significant higher incidence of arterial thrombotic events (coronary, neurological and peripheral vascular events) at the expense of strokes and transient ischaemic attacks (22 vs 2 events in CHD and control patients, respectively). Also, no significant differences were seen in age, sex, BMI, arterial hypertension, diabetes mellitus, dyslipidemia, smoking habit, serum glucose, total and LDL cholesterol, statin treatment, myocardial infarction and arterial thrombotic events according to CHD complexity. Being older and having arterial hypertension, diabetes mellitus, dyslipidemia and smoking habit were more frequent among CHD patients with arterial thrombosis. CONCLUSIONS: Congenital heart diseases are more hypertensive and diabetic but less dyslipemic and smokers than patients in the control group. CHD patients have a higher incidence of neurological events but not of myocardial infarction in relation to the control population.

Anemia in Adolescents and Young Adult Patients With Congenital Heart Disease.

INTRODUCTION: Despite anemia in acquired heart disease being a common problem, little is known in patients with congenital heart disease (CHD). METHODS: In total, 544 consecutive stable noncyanotic CHD patients were studied to determine demographic, clinical, and analytic parameters. Anemia was defined as a condition in which hemoglobin concentration was <13 g/dL in male individuals and <12 g/dL in female individuals. RESULTS: In total, 49 (9%) CHD patients had anemia. Patients with complex anatomy had the highest prevalence of anemia (33%). The median hemoglobin concentration was 14.4 (13.5 to 15.6) mg/dL. Of the total anemic CHD patients, 21 of 49 (43%) were microcytic (mean corpuscular volume <84 fL) and 46 of 49 (94%) had a mean corpuscular volume under 95 fL. Oral anticoagulation, oral antiaggregation, diuretic treatment, and having valve prostheses or cardiovascular risk factors, such as arterial hypertension or diabetes mellitus, did not reach statistical significance between anemic and nonanemic CHD patients. Multivariate analyses determined as risk factors for anemia a worse New York Heart Association functional class (patients in class >II/IV) (odds ratio [OR], 8.37; 95% confidence interval [CI], 1.69-41.35), N-terminal proB-type natriuretic peptide levels >125 pg/mL (OR, 7.90; 95% CI, 2.88-21.69), and apoferritn levels below 15 ng/mL (OR, 0.21; 95% CI, 0.09-0.50). The Kaplan-Meier survival analysis showed no significant differences in mortality between anemic and nonanemic CHD patients (P=0.143). CONCLUSIONS: The incidence of anemia in CHD patients is similar to that of the normal population and iron deficiency anemia accounts for most of the cases. There were no significant differences in mortality between CHD patients with and without anemia.

Novel Marfan Syndrome-Associated Mutation in the FBN1 Gene Caused by Parental Mosaicism and Leading to Abnormal Limb Patterning.

Marfan syndrome is an autosomal dominant disorder of the connective tissue caused by mutations in the fibrillin-1 (FBN1) gene. Mutations affecting cysteine residues within the epidermal growith factor-like calcium-binding domains (EGF_CA) of FBN1 are associated with Marfan syndrome features and, especially, with ectopia lentis. We report a novel substitution, affecting the first cysteine of an EGF_CA-binding module encoded by exon 63 of FBN1 (C2571Y), in a patient presenting with typical Marfan syndrome features but without ectopia lentis. The involvement of this particular carboxi-terminal domain in bone morphogenetic protein signaling is evidenced by patterning defects in the apendicular skeleton shown by the gain of a phalange at digit 1 and the fusion of some wrist bones. Although the mutation appeared as sporadic, detailed analysis revealed that the asymptomatic father was a gonosomal mosaic, and that aproximately 25% of his body cells carry the mutation. Based on this and previous evidence on the origin of sporadic mutations, we would like to stress the importance of detailed parental genetic screening, so the risk of recurrence may be evaluated.

CYP2C19 activity and cardiovascular risk factors in patients with an acute coronary syndrome. / Actividad de CYP2C19 y factores de riesgo cardiovascular en pacientes con síndrome coronario agudo.

INTRODUCTION: CYP2C19 is a major isoform of cytochrome P450 that metabolizes a number of drugs and is involved in the glucocorticoids synthesis. CYP2C19 polymorphisms have been associated with the genetic risk for type 2 diabetes. METHODS: Five hundred and three patients with an acute coronary event were studied to assess the association between the CYP2C19 activity (CYP2C19*2, CYP2C19*3 and CYP2C19*17 variants) and the type of acute coronary syndrome, cardiovascular risk factors (arterial systemic hypertension, diabetes mellitus, dyslipidemia and smoking), analytical parameters and the extent and severity of coronary atherosclerosis. RESULTS: Genotype distribution in our series was similar to that expected in the Caucasian population. Among the traditional cardiovascular risk factors, very poor metabolizer patients (*2/*2, *3/*3 or *2/*3) had a greater tendency to present diabetes mellitus needing insuline (P=.067). Conversely, when we compared very poor, poor and normal metabolizers vs. rapid and ultrarapid metabolizers we found significant differences in those diabetic patients under insulin treatment (64 patients [18%] vs. 17 patients [11%]; P=.032). On the contrary, analytical parameters, systemic arterial hypertension, dyslipidemia, smoking or the personal/family history of coronary artery disease did not reach statistical significance regardless of CYP2C19 activity. Similarly, the number and the type of coronary disease (thrombotic, fibrotic or both) did not differ between patients with different CYP2C19 enzyme activity. CONCLUSION: Patients with an acute coronary event and a very poor, poor and normal CYP2C19 metabolizer genotype have a higher prevalence of diabetes mellitus needing insuline than patients with the rapid and ultrarapid metabolizers CPY2C19 genotype.

Hepatocellular carcinoma in a non-failing Fontan circulation.

Patients after a Fontan operation exhibit some degree of fibrosis which are primarily located in a sinusoidal or centrilobular pattern. Cirrhosis may develop years later and the incidence of cancer is up to 5%. That is why some authors recommend that patients who are >10 years out from their Fontan operation should undergo cardiac assessment as well as the determination of alpha-fetoprotein level, the realization of liver imaging tests or even liver biopsy to stay ahead of neoplastic transformation.

Paraoxonase 1 (Q192R) gene polymorphism, coronary heart disease and the risk of a new acute coronary event.

INTRODUCTION: Paraoxonase 1 (PON1) plays a major role in the oxidation of low density lipoprotein and in the prevention of coronary atherogenesis. In this context, coding region polymorphisms of PON1 gene, responsible for the enzyme activity, has become of interest as a marker for atherogenesis. METHODS: A study and follow-up was conducted on 529 patients with an acute coronary event in order to assess the association between the PON1 Q192R (rs662;A/G) polymorphism, the type of acute coronary syndrome, cardiovascular risk factors (arterial hypertension, diabetes mellitus, dyslipidaemia, and smoking), the extent and severity of coronary atherosclerosis, and the medium-term clinical follow-up. RESULTS: The QQ genotype was found in 245 (46.3%) patients, with 218 (41.2%) patients showing the QR genotype, and 66 (14.5%) patients had the RR genotype. No significant differences were found between the QQ and QR/RR genotypes as regards the clinical characteristics, the analytical data, and the angiographic variables. Similarly, Kaplan-Meier survival analysis showed no significant differences in presenting with a new acute coronary event (p=0.598), cardiac mortality (p=0.701), stent thrombosis (p=0.508), or stent re-stenosis (p=0.598) between QQ and QR/RR genotypes during the follow-up period (3.3±2.2 years). CONCLUSIONS: In patients with an acute coronary syndrome, the PON1 Q192R genotypes did not influence the risk of suffering a new acute coronary event during the medium-term follow-up.

Risks Factors for Atrial Septal Defect Occlusion Device Migration.

Atrial septal defect (ASD) is one of the most common congenital heart defects requiring procedural intervention. In such cases, transcatheter closure of secundum ASDs has been demonstrated to be safe and effective in both children and adults, with similar success and complication rates to surgery. However, appropriate patient selection and an accurate device selection is mandatory to prevent serious complications such as ventricular arrhythmias, outflow tract obstruction of the left and right ventricle, or ischemic events secondary to the obstruction of blood flow due to device embolization.

Severe pulmonary arterial hypertension in an adult patient with total anomalous pulmonary venous connection operated in infancy.

The goal of total anomalous pulmonary venous connection repair is to obtain an unobstructed communication between the pulmonary veins and the left atrium and removing intracardiac shunting. However, pulmonary venous obstruction orstenosis may be seen in 5-10% of patients, is usually evident in the first 6 months following surgery and may lead to pulmonary congestion, pulmonary arterial hypertension, and late mortality. In such cases, early intervention may be indicated before irreversible secondary changes occur. We present the case and the therapeutic approach of an adolescent patient with total anomalous pulmonary venous drainage to the superior vena cava operated in infancy who developed pulmonary venous obstruction and secondary severe pulmonary arterial hypertension.

[Difficulties in the percutaneous approach of the acute coronary syndrome with associated axillobifemoral bypass]. / Dificultades en el abordaje percutáneo del síndrome coronario agudo con bypass axilobifemoral.

BACKGROUND: Peripheral arterial disease and coronary artery disease are frequently associated. The percutaneous approach may sometimes involve additional difficulties to the coronary artery disease. CLINICAL CASE: The case is presented on an 82 year-old male patient with multiple cardiovascular risk factors, a Leriche syndrome and axillobifemoral bypass, who was admitted to hospital due to an inferior myocardial infarction. The procedure approach (radial, brachial, or femoral access routes for percutaneous coronary treatment) and associated complications from the procedure are discussed. CONCLUSION: Although technical improvements and/or treatment of peripheral vascular lesions may allow percutaneous coronary intervention, individual risk and benefit in each patient must be assessed.

Hipertensión arterial oculta tras coartación de aorta corregida / Occult arterial hypertension after repaired aortic coarctation

La coartación de aorta es una de las cardiopatías congénitas intervenidas más frecuentes en la edad adulta. En estos pacientes, hay una mayor incidencia de hipertensión arterial durante las actividades diarias y el ejercicio, a pesar de una correcta cirugía reparadora. Dado que la hipertensión arterial, en ocasiones, solo se demuestra al realizar un monitoreo de la tensión arterial (hipertensión arterial oculta), debemos también estar atentos a la aparición de signos indirectos, como el desarrollo de hipertrofia ventricular izquierda.

Coarctation of the aorta, repaired in childhood, is a congenital heart disease frequently seen in adulthood. In these patients there is a higher incidence ofhypertension during daily activities and exercise despite a correct surgical repair. Since hypertension may only be seen by ambulatory blood pressure monitoring (occult arterial hypertension) we should also look for indirect signs, such as the development of left ventricular hypertrophy.

[Pregnancy and coronary artery dissection]. / Embarazo y disección arterial coronaria.

Acute myocardial infarction during pregnancy is associated with high maternal and fetal mortality. Coronary atherosclerosis is the most common cause due to an increase in the age of the patients and the association with cardiovascular risk factors such as smoking, hypertension, diabetes mellitus, preeclampsia, and the existence of family history of coronary disease. However, thrombosis, coronary dissection or coronary vasospasms are other causes that may justify it. We report the case of a 33 weeks pregnant first-time mother, without cardiovascular risk factors, who presented an acute coronary event in the context of atherosclerotic disease and coronary dissection after percutaneous coronary intervention.