Publications by authors named "Efrén Martínez-Quintana"

99 Publications

Gamma-glutamyl transferase and cardiovascular events in patients with congenital heart disease.

Eur J Clin Invest 2021 Nov 24:e13720. Epub 2021 Nov 24.

Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain.

Introduction: Serum gamma-glutamyltransferase activity (GGT) seems to predict cardiovascular events in different populations. However, no data exist on patients with congenital heart disease (CHD).

Methods: Observational, analytic, prospective cohort study design involving CHD patients and a control population to determine the effect of GGT levels on survival.

Results: 589 CHD patients (58% males, 29 ± 14 years old) and 2745 matched control patients were followed up. 69 (12%) CHD patients had a major acute cardiovascular event (MACE) during the follow up time [6.1 (0.7-10.4) years]. Patients with CHD and a GGT > 60 U/L were significantly older, more hypertensive and dyslipedemic, had a worse NYHA functional class and a greater anatomical complexity than CHD patients with a GGT ≤ 60 U/L. The binary logistic regression analysis showed that age, a great CHD anatomical complexity, and having atrial fibrillation/flutter were predictive factors of higher GGT levels (> 60 U/L). The Kaplan-Meier analysis showed that patients with CHD and a GGT concentration above 60 UL showed the lowest probability of survival compared to CHD with GGT ≤ 60 U/L and controls irrespective of their GGT concentrations (p<0.001). Similarly, the multivariable Cox regression analysis found an independent association between higher GGT levels (> 60 U/L) and a worse prognosis [HR 2.44 (1.34-4.44), p=0.003] among patients with CHD.

Conclusion: Patients with CHD showed significant higher GGT levels than patients in the control group having those with higher GGT concentrations (> 60 U/L) the worst survival.
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http://dx.doi.org/10.1111/eci.13720DOI Listing
November 2021

COVID-19 quarantine and depression in patients with congenital heart disease.

Am J Cardiovasc Dis 2021 15;11(1):80-86. Epub 2021 Feb 15.

Research Unit, Complejo Hospitalario Universitario Insular-Materno Infantil Las Palmas de Gran Canaria 35016, Spain.

COVID-19 outbreak has brought tremendous psychological pressure to the general population, especially to those with associated cardiovascular disease. An online Patient Health Questionnaire (PHQ-9) survey on consecutive congenital heart disease (CHD) patients, was carried out to determine depression during the Spanish coronavirus disease (COVID-19) quarantine. Two-hundred forty-two out of 407 (59%) CHD patients answered the survey, 123 (51%) had mild defects, 88 (36%) moderate and 31 (13%) great defects, most of them between 18 and 24 years old and 51% were male. Patients were dichotomized to no or mild (PHQ-9 < 10) and moderate to severe (≥ 10) depressive symptoms. Thirty-four (14%) patients showed a PHQ-9 ≥ 10 and 10 of them (29%) were under anxiolytic or antidepressant treatment during the quarantine. During the study period, 9 (4%) patients had COVID-19 symptoms. Patients with a NYHA above 2 (P=0.025), living in houses without garden or balcony (P=0.014), needing psychological/psychiatric evaluation/medication in the previous 12 months or being under anxiolytic/antidepressant treatment during the confinement had, significantly, a PHQ-9 score ≥ 10 (P < 0.001). Being under anxiolytic/antidepressant treatment during the coronavirus pandemic [OR 3.92 (95% CI 1.05-14.66), P=0.043] and having previous psychological/psychiatric evaluation in the previous 12 months to the quarantine [OR 3.82 (95% CI 1.16-12.54), P=0.027] were the only variables that reached statistical significance, in the multivariable analysis, as predictors of a pathological PHQ-9 questionnaire (score ≥ 10). In conclusion depression was frequent during the COVID-19 quarantine among CHD patients, with only a third of them being under anxiolytic or antidepressant treatment. Needing psychological/psychiatric evaluation/treatment during the previous 12 months to the lockdown was a predictive factor for an abnormal PHQ-9 score.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012290PMC
February 2021

Evaluation of quality of life in patients with congenital heart disease: an observational case control study.

Am J Cardiovasc Dis 2021 15;11(1):73-79. Epub 2021 Feb 15.

Ophthalmology Service, Hospital Universitario de Gran Canaria Dr. Negrín Las Palmas de Gran Canaria, Spain.

Quality of life (QoL) has become an important issue in patients with congenital heart disease (CHD). Accordingly, the focus has shifted from mere survival to a better QoL. The objective of this study is to assess QoL, by examining the World Health Organization QoL-bref (WHOQoL-BREF) questionnaire, in patients with CHD and a control population of a same geographic area matched for age, sex, cardiovascular risk factors and educational level. 154 patients with CHD recruited from a single hospital outpatient clinic and 250 healthy controls were studied between October 2018 and April 2019. Median age in patients with CHD was 27 (20-34) years and 62% were male. 32, 90 and 32 patients with CHD showed mild, moderate, and complex defects, respectively. 131 (53%) controls referred having felt or experienced negative feelings such as bad mood, despair, stress, or depression compared to 53 (34%) patients in the CHD group (P<0.001). Despite needing more medical treatment (P<0.001), patients with CHD enjoyed more their lives (P<0.001), felt their lives made more sense (P<0.001), were happier with themselves (P=0.006) and with their personal relationships (P=0.020), had a greater support from friends (P=0.031) and felt safer in their daily lives (P=0.004) than patients in the control group. Similarly, patient with CHD felt their environment was healthier, had more opportunities for leisure and were happier with their access to healthcare system (P<0.005) than controls. On the contrary, except the need for more medical treatment in patients with great CHD defects (P=0.019), no significant differences were seen in the WHOQoL-BREF survey according to the anatomical complexity. In conclusion, overall patients with CHD scored better in the WHOQoL-BREF questionnaire, especially in the psychological and environment domains, than patients in the control group.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012282PMC
February 2021

The effect of physical activity on quality of life and serum glucose and cholesterol levels in patients with congenital heart disease.

Am J Cardiovasc Dis 2021 15;11(1):53-64. Epub 2021 Feb 15.

Research Unit. Complejo Hospitalario Universitario Insular-Materno Infantil Las Palmas de Gran Canaria 35016, Spain.

As physical activity contributes to quality of life and health, we evaluated its association, as measured by the Global physical activity (GPAQ) questionnaire, on the quality of life (QoL) and serum glucose and cholesterol levels of patients with congenital heart disease (CHD). This cross-sectional study was carried out in 200 adult patients with CHD (17 to 58 years old), of whom 45 had simple defects, 122 moderate defects and 33 great anatomical complexity defects. Physiological complexity was defined as stage A in 74 patients, stage B in 29, stage C in 86 and stage D in 11. The energy expenditure was below 600 Metabolic Equivalent of Task (MET)-minutes per week in 56 (28%) patients, while 144 (72%) were above 600 MET-minutes per week. Physically inactive patients with CHD were significantly more dyslipidemic than active ones, but no significant differences in serum glucose and cholesterol levels were observed. Logistic regression analysis showed that physical activity was associated with a better QoL rating [0.28 (0.10-0.17), P=0.014] and health satisfaction [0.24 (0.09-0.62), P=0.003]. Physically active patients with CHD scored 7.7 and 8.9 points higher, on a 100-point scale, in the physical and social relationships domains respectively, than physically inactive ones. No significant differences were seen in the psychological and the environment domains associated with physical activity. Additionally, a worse New York Heart Association (NYHA) functional class (≥ 2) was identified as a risk factor for dissatisfaction with health [OR 7.48, 95% CI (1.55-47.14), P=0.020], having a significantly negative impact of 8.5 and 7.6, on a 100-point scale, in the physical and psychological domains respectively. In conclusion, physically active patients with CHD had a better QoL assessment, were more satisfied with their health and scored higher in the physical and social relationships domains.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012286PMC
February 2021

Proteinuria versus albuminuria in 24-hour urine collection: prevalence and clinical outcome in non-hypoxemic adult patients with congenital heart disease.

Am J Cardiovasc Dis 2021 15;11(1):46-52. Epub 2021 Feb 15.

Hospital Universitario de Gran Canaria Dr. Negrín Las Palmas de Gran Canaria, Spain.

Congenital heart disease (CHD) patients, especially cyanotic ones, usually have renal function impairment. However, little information exists in non-cyanotic CHD patients. The objective of this study is to determine renal failure in non-hypoxemic CHD patients by measuring the amount of protein and albumin released in urine over a 24-hour period and determining the glomerular filtration rate (GFR). Prospective study of consecutive outpatient non-hypoxemic CHD patients followed up in a single tertiary referral hospital. Demographic, clinical, blood test and 24-hour urine collection were recorded. 264 CHD patients, 22 (18-343) years old and 160 (61%) males, were followed up during 9.2 (5.9-11.1) years. 137 (52%), 96 (36%) and 31 (18%) CHD patients had mild, moderate, and great anatomical CHD defects. 44 (17%) and 32 (12%) CHD patients showed proteinuria (≥ 150 mg/24 hours) and albuminuria (> 30 mg/24 hours) respectively. 35 out of 44 (79%) CHD patients with proteinuria (≥ 150 mg/24 hours) showed normal to mild albuminuria levels (< 30 mg/24 hours). Variables associated with proteinuria were male sex, body mass index, auricular fibrillation/flutter, arterial hypertension, diabetes mellitus and being under angiotensin-converting enzyme (ACE) inhibitor and an angiotensin receptor blocker (ARB), loop diuretics or anti-aldosterone treatment. Major adverse cardiovascular events (MACE), defined as cardiovascular and non-cardiovascular deaths, stroke, myocardial infarction and heart failure requiring hospitalization, occurred in 16 (6%) patients during the follow up time. Multivariate Cox regression analysis showed that older patients, patients with a great CHD complexity and patients with proteinuria [6.99 (1.90-24.74), P=0.003] had a significant higher risk of MACE. Proteinuria is frequent among non-hypoxemic CHD patients and occurs mostly in those with a GFR above 60 ml/min/1.73 m and normal to mild albuminuria levels. Having proteinuria, but not albuminuria, was independently associated with a worse outcome.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012297PMC
February 2021

COVID-19 in Adults With Congenital Heart Disease.

J Am Coll Cardiol 2021 04;77(13):1644-1655

Division of Cardiology, Medical University of South Carolina, Charleston, South Carolina, USA.

Background: Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications.

Objectives: This study sought to define the impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes.

Methods: Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide. Data collection included anatomic diagnosis and subsequent interventions, comorbidities, medications, echocardiographic findings, presenting symptoms, course of illness, and outcomes. Predictors of death or severe infection were determined.

Results: From 58 adult CHD centers, the study included 1,044 infected patients (age: 35.1 ± 13.0 years; range 18 to 86 years; 51% women), 87% of whom had laboratory-confirmed coronavirus infection. The cohort included 118 (11%) patients with single ventricle and/or Fontan physiology, 87 (8%) patients with cyanosis, and 73 (7%) patients with pulmonary hypertension. There were 24 COVID-related deaths (case/fatality: 2.3%; 95% confidence interval: 1.4% to 3.2%). Factors associated with death included male sex, diabetes, cyanosis, pulmonary hypertension, renal insufficiency, and previous hospital admission for heart failure. Worse physiological stage was associated with mortality (p = 0.001), whereas anatomic complexity or defect group were not.

Conclusions: COVID-19 mortality in adults with CHD is commensurate with the general population. The most vulnerable patients are those with worse physiological stage, such as cyanosis and pulmonary hypertension, whereas anatomic complexity does not appear to predict infection severity.
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http://dx.doi.org/10.1016/j.jacc.2021.02.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006800PMC
April 2021

Mediterranean diet adherence in patients with congenital heart disease.

Am J Cardiovasc Dis 2020 15;10(5):569-577. Epub 2020 Dec 15.

Dr. Negrín University Hospital of Gran Canaria Las Palmas de Gran Canaria, 35019, Spain.

The Mediterranean diet, based on a rural life where people ate what they grew, has shown cardiovascular benefits. Cross-sectional study of congenital heart disease (CHD) patients recruited consecutively from a single hospital outpatient clinic with the aim of determining their adherence to the Mediterranean diet according to the PREDIMED questionnaire. CHD complexity was categorized as simple, moderate, or great and demographic, clinical and blood test data were recorded. 200 CHD patients, median age 28 (16-54) years old and 120 (60%) males were studied. 45 (22.5%), 122 (61%) and 33 (16.5%) CHD patients had simple, moderate, and great complexity defects respectively. PREDIMED score was classified as low (score 0-5), intermediate (6-9) or high (> 9). 146 (83%) CHD patients showed a suboptimal Mediterranean diet adherence (PREDIMED score < 9) with less than half of patients eating enough vegetables, fruits, legumes, fish or nuts but with a high intake of butter/margarine, commercial sweets and carbonated beverages. No significant differences were seen between sex, body mass index, cardiovascular risk factors, CHD complexity or the educational level and the PREDIMED scores. Only being married was associated with a significant lower Mediterranean diet adherence (P=0.019). Meanwhile, no statistical significance was observed between serum glucose, creatinine, uric acid, albumin, LDL cholesterol, HDL cholesterol or triglycerides levels according to the PREDIMED classification (low, intermediate or high adherence). Conclusions: CHD patients have a low adherence to the Mediterranean diet with a low intake of vegetables, fruits, legumes, and fish.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811916PMC
December 2020

Malnutrition is independently associated with an increased risk of major cardiovascular events in adult patients with congenital heart disease.

Nutr Metab Cardiovasc Dis 2021 02 28;31(2):481-488. Epub 2020 Sep 28.

Research Unit, Complejo Hospitalario Universitario Insular- Materno Infantil, Las Palmas de Gran Canaria, Spain.

Background And Aims: Malnutrition is found frequently during chronic diseases, and its prevalence and relation to disease outcome in adult patients with congenital heart disease (CHD) remains unknown.

Methods And Results: A cohort of 393 consecutive stable congenital heart disease (CHD) patients was followed up in a single dedicated clinical unit. Demographic, clinical and laboratory parameters, along with a nutritional risk index (NRI), were studied, as well as major acute cardiovascular events (MACE), defined as arterial thrombotic events, heart failure requiring hospitalization or cardiovascular and non-cardiovascular mortality. The median age of the patients was 23 years (17-35) and 225 (57%) were males. Median plasma albumin concentration was 4.5 (4.2-4.7) g/dL, the body mass index was 23 (21-27) kg/m, the NRI was 112 (106-118), and 33 (8%) patients showed malnutrition (NIR<100). A worse NYHA functional class (II and III), total cholesterol and serum glucose levels were significant risk factors associated with malnutrition (NRI<100) in CHD patients. During a median follow-up of 8 (5-10) years, 39 (10%) CHD patients suffered a MACE. Multivariable Cox regression analysis showed that older patients (years) [HR 1.06 (1.04-1.09), p < 0.001], CHD patients with great anatomical complexity [HR 4.24 (2.17-8.27), p < 0.001] and those with a lower NRI [HR 0.95 (0.93-0.98), p = 0.001] had a significant worse MACE-free survival, being the NRI a better predictor of MACE than albumin concentration.

Conclusions: A low NRI is independently associated with a significant increased risk of MACE in CHD patients.
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http://dx.doi.org/10.1016/j.numecd.2020.09.026DOI Listing
February 2021

Red blood cell distribution width in addition to N-terminal prohormone of B-type natriuretic peptide concentration improves assessment of risk of cardiovascular events in adult patients with congenital heart disease.

Arch Cardiovasc Dis 2020 Oct 7;113(10):607-616. Epub 2020 Oct 7.

Research Unit, Complejo Hospitalario Universitario Insular-Materno Infantil, 35016 Las Palmas de Gran Canaria, Spain.

Background: Red blood cell distribution width (RDW) is a predictor of adverse outcomes in patients with heart disease.

Aim: To establish predictors of high RDW values in patients with congenital heart disease (CHD), and their relationship with cardiovascular events.

Methods: Overall, 561 patients with stable CHD who attended a single outpatient clinic and a matched control population of 2128 patients were studied. Exclusion criteria were renal failure, anaemia, receiving iron therapy and cyanosis. Blood tests included glucose, creatinine, iron, apoferritin, liver enzymes and a complete blood count. C-reactive protein and N-terminal prohormone of B-type natriuretic peptide (NT-pro-BNP) concentrations were also measured in patients with CHD. Major adverse cardiac events (MACE) were defined as cardiovascular/total mortality, arterial thrombotic events, arrhythmias, major bleedings, pulmonary embolism or heart failure needing hospital admission.

Results: The median age in patients with CHD was 23 (17-36) years and the median follow-up time was 5.8 (3.2-8.7) years; 103 (4.8%) controls and 40 (7.1%) patients with CHD had an RDW>15% (P=0.032). During follow-up, MACE were reported in 48 patients. CHD of great complexity, cardiovascular risk factors, low haemoglobin concentration and high NT-pro-BNP concentration were risk factors for an RDW>15%. Kaplan-Meier analysis showed a significantly worse cardiovascular outcome in patients with CHD with an RDW>15% (P<0.001). The multivariable survival analysis determined that age, CHD of great complexity, high NT-pro-BNP concentration and an RDW>15% were independent predictive factors for MACE.

Conclusion: RDW and NT-pro-BNP concentration are independent analytical predictors of MACE in patients with CHD.
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http://dx.doi.org/10.1016/j.acvd.2020.05.019DOI Listing
October 2020

Predicting sudden cardiac death in adults with congenital heart disease.

Heart 2021 01 16;107(1):67-75. Epub 2020 Jun 16.

Adult Congenital Heart Disease Unit, Department of Cardiology, Hospital General Universitario Gregorio Marañon, Instituto de Investigación Sanitaria Gregorio Marañón, Facultad de Medicina, Universidad Complutense de Madrid and CIBERCV, Madrid, Spain.

Objectives: To develop, calibrate, test and validate a logistic regression model for accurate risk prediction of sudden cardiac death (SCD) and non-fatal sudden cardiac arrest (SCA) in adults with congenital heart disease (ACHD), based on baseline lesion-specific risk stratification and individual's characteristics, to guide primary prevention strategies.

Methods: We combined data from a single-centre cohort of 3311 consecutive ACHD patients (50% male) at 25-year follow-up with 71 events (53 SCD and 18 non-fatal SCA) and a multicentre case-control group with 207 cases (110 SCD and 97 non-fatal SCA) and 2287 consecutive controls (50% males). Cumulative incidences of events up to 20 years for specific lesions were determined in the prospective cohort. Risk model and its 5-year risk predictions were derived by logistic regression modelling, using separate development (18 centres: 144 cases and 1501 controls) and validation (two centres: 63 cases and 786 controls) datasets.

Results: According to the combined SCD/SCA cumulative 20 years incidence, a lesion-specific stratification into four clusters-very-low (<1%), low (1%-4%), moderate (4%-12%) and high (>12%)-was built. Multivariable predictors were lesion-specific cluster, young age, male sex, unexplained syncope, ischaemic heart disease, non-life threatening ventricular arrhythmias, QRS duration and ventricular systolic dysfunction or hypertrophy. The model very accurately discriminated (C-index 0.91; 95% CI 0.88 to 0.94) and calibrated (p=0.3 for observed vs expected proportions) in the validation dataset. Compared with current guidelines approach, sensitivity increases 29% with less than 1% change in specificity.

Conclusions: Predicting the risk of SCD/SCA in ACHD can be significantly improved using a baseline lesion-specific stratification and simple clinical variables.
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http://dx.doi.org/10.1136/heartjnl-2020-316791DOI Listing
January 2021

Prevalence and predictors of psychological distress in congenital heart disease patients.

J Clin Psychol 2020 09 9;76(9):1705-1718. Epub 2020 Mar 9.

Research Unit, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de Gran Canaria, Spain.

Objective: To determine psychological distress in congenital heart disease (CHD) patients.

Methods: Cross-sectional study among consecutive CHD patients recruited from a single hospital outpatient clinic to determine anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS) questionnaire.

Results: One hundred and sixty-nine CHD patients [29 (19-39) years old, 100 (59%) males] were studied. A total of 25% and 9% of CHD patients showed anxiety and depression symptoms, respectively. Patients with an HADS score ≥ 8 had a significantly worse New York Heart Association (NYHA) functional class, needed more psychological support, had more mental health history, and took more anxiolytic/antidepressant medication than the CHD patients with an HADS score below 8. A worse NYHA functional class [OR, 1.88 (1.01-3.52)] proved to be a predictor of a borderline/abnormal HADS score.

Conclusion: Psychological distress has a high prevalence among CHD patients and having an NYHA Class II and III is a significant predictor of an HADS score ≥ 8.
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http://dx.doi.org/10.1002/jclp.22948DOI Listing
September 2020

Truncus arteriosus and truncal valve regurgitation.

Transl Pediatr 2019 Dec;8(5):360-362

Cardiac Surgery Service, Dr. Negrín University Hospital of Gran Canaria, Las Palmas de Gran Canaria, Spain.

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http://dx.doi.org/10.21037/tp.2019.02.01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970119PMC
December 2019

Anterior spinal artery syndrome and aortic dissection.

Cir Cir 2019 ;87(4):466-469

Servicio de Oftalmología, Hospital Universitario de Gran Canaria Dr. Negrín. Las Palmas de Gran Canaria, España.

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.
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http://dx.doi.org/10.24875/CIRU.18000357DOI Listing
January 2020

Giant right pulmonary artery aneurysm in a systemic-to-pulmonary artery shunt.

Cardiol Young 2019 Jun 14;29(6):835-836. Epub 2019 Jun 14.

Radiology Service, Insular-Materno Infantil University Hospital,Las Palmas de Gran Canaria,Spain.

Aneurysms of the pulmonary arteries and trunk are rare entities. The Waterston shunt is a palliative procedure for children with cyanotic CHD due to obstruction of the pulmonary outflow. Described complications are distortion of the pulmonary artery and pulmonary arterial hypertension. We report a patient with a giant right pulmonary artery aneurysm in relation to a Waterston shunt.
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http://dx.doi.org/10.1017/S1047951119001343DOI Listing
June 2019

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

Int J Clin Pract 2019 Sep 28;73(9):1-8. Epub 2019 Jun 28.

Medical and Surgical Sciences Department, Faculty of Health Sciences, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.

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.
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http://dx.doi.org/10.1111/ijcp.13378DOI Listing
September 2019

Mean platelet volume and major adverse cardiovascular events in congenital heart disease patients.

Clin Hemorheol Microcirc 2019 ;72(4):327-337

Ophthalmology Service, Dr. Negrín University Hospital of Gran Canaria, Las Palmas de Gran Canaria, Spain.

Background: Platelet activation is linked with thrombosis, inflammation or heart failure.

Objective: To establish clinical and analytical factors that may favor high mean platelet volume (MPV) and to determine if MPV levels favor major adverse cardiovascular events (MACE).

Methods: Stable CHD patients and a control population matched for age, sex and cardiovascular factors.

Results: 658 CHD patients and 2092 controls were studied. Median age in CHD patients was 33 (25-41) year old with 56% of them being male. No significant differences were seen between MPV values and cardiac complexity (p = 0.308) nor between MPV values in the CHD and control groups (p = 0.911). CHD patients had significant lower platelet count and MPV levels than patients in the control group. In the binary logistic regression analysis NT-pro-BNP levels above 125 pg/ml, thrombocytopenia and having atrial fibrillation/flutter reached statistical significance as predictors of MPV levels above 11 fL. The Kaplan-Meier survival analysis showed no significance between MPV levels higher than 11 fL and MACE, cardiovascular mortality and thrombotic events in a median time follow-up of 6.7(1.5-10.6) years.

Conclusions: Atrial fibrillation/flutter, heart failure and thrombocytopenia are predictors of high MPV levels. A MPV above 11 fL is not associated with MACE at a median follow-up time.
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http://dx.doi.org/10.3233/CH-180471DOI Listing
December 2019

Neuroendocrine tumors and conotruncal cardiac defects.

J Cardiovasc Thorac Res 2018 10;10(3):180-181. Epub 2018 Sep 10.

Ophthalmology Service. Dr. Negrín University Hospital of Gran Canaria. Las Palmas de Gran Canaria, Spain.

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http://dx.doi.org/10.15171/jcvtr.2018.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203865PMC
September 2018

Red cell distribution width in congenital heart disease patients: Beyond cardiovascular events.

Int J Cardiol 2018 11;270:135

Ophthalmology Service, Dr. Negrín University Hospital of Gran Canaria, Las Palmas de Gran Canaria, Spain.

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http://dx.doi.org/10.1016/j.ijcard.2018.06.118DOI Listing
November 2018

Risk factors for hyperuricemia in congenital heart disease patients and its relation to cardiovascular death.

Congenit Heart Dis 2018 Sep 31;13(5):655-662. Epub 2018 Jul 31.

Cardiology Service, Insular-Materno Infantil University Hospital, Las Palmas de Gran Canaria, Spain.

Introduction: Hyperuricemia has been associated with cardiovascular risk factors but it remains controversial if uric acid is an independent predictor of cardiac mortality.

Methods: A total of 503 CHD patients (457 nonhypoxemic and 46 hypoxemic) and 772 control patients fulfilled inclusion criteria. Demographic, clinical, and analytical data [serum uric acid and 24h urine uric acid levels, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), and C-reactive-protein (CRP) concentrations] were studied. Survivals curves to determine cardiac death and arterial thrombosis in CHD patients were also examined.

Results: Noncyanotic and cyanotic CHD patients had significant higher serum uric acid concentration (5.2 ± 1.5 vs 4.9 ± 1.3mg/dL, P = .007 and 6.7 ± 2.1 vs 4.9 ± 1.3mg/dL, P < .001, respectively) and gout (1% vs 0%, P = .003 and 4% vs 0%, P < .01, respectively) than the control population. Among CHD patients, hyperuricemic patients were significant older and with overweight, used more diuretics, were more cyanotic and had higher serum creatinine, NT-pro-BNP and CRP concentrations than nonhyperuricemic. In the multivariable analysis, the body mass index (BMI) (OR 1.09; 95% CI 1.01-1.18), cyanosis (OR 6.2; 95 CI 1.5-24.6), serum creatinine concentration (OR 49; 95% CI 44-538), and being under diuretic treatment (OR 4.5; 95% CI 1.4-14.5) proved to be risk factors for hyperuricemia in CHD patients. The Kaplan-Meier events free survival curves, during a 5.2 ± 2.7 years follow-up of up time, showed that hyperuricemic CHD patients had significant higher cardiovascular death (P = .002). However, after applying the Cox regression analysis uric acid levels lost its statistical significance. No significant differences were seen in relation to thrombotic events between CHD patients with and without hyperuricemia.

Conclusions: CHD patients, noncyanotic and cyanotic, have higher serum uric acid levels and gout than patients in the general population. BMI, renal insufficiency, cyanosis, and the use of diuretics were risk factor for hyperuricemia among CHD patients.
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http://dx.doi.org/10.1111/chd.12620DOI Listing
September 2018

CYP2C19 or CYP3A5 Genotyping Does Not Predict Clinical Response to Clopidogrel.

J Clin Pharmacol 2018 10 3;58(10):1274-1283. Epub 2018 May 3.

Research Unit, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de Gran Canaria, Spain.

Along with aspirin, clopidogrel has been a widely used antiplatelet therapeutic regimen. Although generally well tolerated, its efficacy varies among individuals, with the main hypothesis that its bioavailability relies on its bioconversion to the active compound, which, in turn, depends on the genetic background and/or interactions with other drugs. To determine which factors influenced response in our patients, 368 patients receiving combined antiaggregation therapy with aspirin and clopidogrel were followed for 1 year to record 30 novel cardiovascular acute events. This clinical relapse was considered a surrogate end point to measure therapeutic response under the influence of the CYP2C19*2, *3, and *17 and CYP3A5*3 alleles, as well as the effects of concomitant medication and the presence of known cardiovascular risk factors and comorbidity. We show that either single CYP2C19 or CYP3A5 genotyping or combined were not useful to predict clinical efficacy in this cohort. Rather than genetic testing, we have found that clinical observations such as suffering type 2 diabetes mellitus requiring insulin, having several vessels affected, and concurrent medication with calcium channel blockers, regardless of CYP3A5 genotype or drug class were, in that order, the strongest independent predictors of disease relapse.
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http://dx.doi.org/10.1002/jcph.1144DOI Listing
October 2018

Clinical, echocardiographic and analytical parameters in patients with atrioventricular septal defect with and without Down syndrome.

Med Clin (Barc) 2018 12 2;151(11):461-463. Epub 2018 Mar 2.

Servicio de Cardiología, Complejo Hospitalario Universitario Insular-Materno Infantil, Las Palmas de Gran Canaria, Las Palmas, España; Departamento de Ciencias Médicas y Quirúrgicas, Facultad de Ciencias de la Salud, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Las Palmas, España. Electronic address:

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http://dx.doi.org/10.1016/j.medcli.2018.01.005DOI Listing
December 2018

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

J Pediatr Hematol Oncol 2018 11;40(8):620-624

Cardiology Service, Insular-Materno Infantil University Hospital.

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.
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http://dx.doi.org/10.1097/MPH.0000000000001115DOI Listing
November 2018

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

Mol Syndromol 2017 May 31;8(3):148-154. Epub 2017 Mar 31.

Research Unit, Complejo Hospitalario Universitario Insular-Materno Infantil, Las Palmas de Gran Canaria, Spain.

Marfan syndrome is an autosomal dominant disorder of the connective tissue caused by mutations in the fibrillin-1 () 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 (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.
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http://dx.doi.org/10.1159/000467909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5448450PMC
May 2017

Hepatocellular carcinoma in a non-failing Fontan circulation.

Rev Esp Enferm Dig 2017 May;109(5):375

Hospital Universitario Dr. Negrín de Gran Canaria, España.

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.
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May 2017

CYP2C19 activity and cardiovascular risk factors in patients with an acute coronary syndrome.

Med Clin (Barc) 2017 Sep 2;149(6):235-239. Epub 2017 May 2.

Unidad de Investigación, Hospital Universitario Insular-Materno Infantil, Las Palmas de Gran Canaria, España.

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.
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http://dx.doi.org/10.1016/j.medcli.2017.02.035DOI Listing
September 2017

Right ventricular function and N-terminal pro-brain natriuretic peptide levels in adult patients with simple dextro-transposition of the great arteries.

Echocardiography 2017 Jun 29;34(6):876-880. Epub 2017 Mar 29.

Dr. Negrín University Hospital of Gran Canaria, Las Palmas de Gran Canaira, Spain.

Introduction: Dextro-transposition of the great arteries (d-TGA) patients is at high risk of developing right ventricular dysfunction and tricuspid regurgitation in adulthood. Determining the relation between echocardiographic parameters, N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels and the New York Heart Association (NYHA) functional class may help determining the best time to operate them.

Methods: Patients with simple d-TGA operated in infancy with an atrial switch procedure (Mustard or Senning operation) were followed up in our Adult Congenital Heart Disease Unit. Analytical, echocardiographic, and clinical parameters were determined to evaluate the correlation between right echocardiographic ventricular function, NT-pro-BNP levels, and NYHA functional class.

Results: Twenty-four patients with d-TGA were operated in infancy of whom 17 alive patients had simple d-TGA. Nine patients had NT-pro-BNP levels lower than 200 pg/mL and eight patients were above 200 pg/mL. Patients with lower hemoglobin concentration, higher right ventricular diameter or under diuretic treatment showed significant higher NT-pro-BNP levels (above 200 pg/dL). The Spearman test showed a positive correlation between basal right ventricular diameter and tricuspid regurgitation with pro NT BNP levels (correlation coefficient of .624; P=.017 and .490; P=.046, respectively) and a negative correlation with the right ventricle fractional area change (-.508, P=.045). No correlation was seen between NT-pro-BNP levels and the rest of echocardiographic parameters or the NYHA functional class.

Conclusion: NT-pro-BNP levels showed a positive correlation with basal right ventricular diameter and tricuspid regurgitation but not with NYHA association functional class in d-TGA patients.
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http://dx.doi.org/10.1111/echo.13526DOI Listing
June 2017

Adrenal mass in a patient with tetralogy of Fallot: beyond expected.

J Cardiovasc Thorac Res 2016 30;8(4):190-191. Epub 2016 Dec 30.

Dr. Negrín University Hospital of Gran Canaria, Las Palmas de Gran Canaria, Spain.

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http://dx.doi.org/10.15171/jcvtr.2016.38DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5304104PMC
December 2016

Liver Imaging in Patients With Fontan Circulation.

Rev Esp Cardiol (Engl Ed) 2017 06 18;70(6):517-518. Epub 2017 Jan 18.

Servicio de Oftalmología, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain.

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http://dx.doi.org/10.1016/j.rec.2016.12.030DOI Listing
June 2017

Serum uric acid levels and cardiovascular disease: the Gordian knot.

J Thorac Dis 2016 Nov;8(11):E1462-E1466

Dr. Negrín University Hospital of Gran Canaria, Las Palmas de Gran Canaria, Spain.

Hyperuricemia is defined as serum uric acid level of more than 7 mg/dL and blood levels of uric acid are causally associated with gout, as implicated by evidence from randomized clinical trials using urate lowering therapies. Uric acid as a cardiovascular risk factor often accompanies metabolic syndrome, hypertension, diabetes, dyslipidemia, chronic renal disease, and obesity. Despite the association of hyperuricemia with cardiovascular risk factors, it has remained controversial as to whether uric acid is an independent predictor of cardiovascular disease. To settle this issue, and in the absence of large randomized controlled trials, Mendelian randomization analysis in which the exposure is defined based on the presence or absence of a specific allele that influences a risk factor of interest have tried to shed light on this.
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http://dx.doi.org/10.21037/jtd.2016.11.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5179380PMC
November 2016

Hereditary Hemorrhagic Telangiectasia and Myocardial Infarction.

Int J Angiol 2016 Dec 18;25(5):e81-e83. Epub 2015 May 18.

Cardiology Service, Insular-Materno Infantil University Hospital, Las Palmas de Gran Canaria, Spain.

Hereditary hemorrhagic telangiectasia, also known as Osler-Weber-Rendu syndrome, is an autosomal dominant genetic disorder that leads to epistaxis, gastrointestinal bleeding, iron deficiency anemia, and arteriovenous malformations at the lungs, the liver, and the brain. However, due to its rarity and its unspecific findings on routine examinations, diagnosis is not easy unless suspected due to hypoxemia or paradoxical embolism. We present a case of a 46-year-old-woman with hereditary hemorrhagic telangiectasia and hypoxemia who presented a myocardial infarction secondary to paradoxical embolism through pulmonary arteriovenous malformations.
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http://dx.doi.org/10.1055/s-0035-1551795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5186306PMC
December 2016
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