Publications by authors named "Jorge Solis"

54 Publications

Subclinical Liver Disease is Associated with Subclinical Atherosclerosis in Psoriasis: Results from Two Observational Studies.

J Invest Dermatol 2021 Jul 19. Epub 2021 Jul 19.

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Psoriasis is associated with a higher risk of liver diseases. We investigated the impact of hepatic steatosis (European cohort) and hepatic inflammation (United States cohort) on subclinical atherosclerosis. In the European cohort (n=76 psoriasis participants and 76 controls), non-alcoholic fatty liver disease (NAFLD), assessed by the sonographic hepatorenal index (SHRI), was more prevalent in psoriasis than controls (61% vs 45%; p=.04). Psoriasis participants with NAFLD had a higher prevalence of subclinical atherosclerosis (ultrasonographic presence of plaque in femoral or carotid arteries) than psoriasis without NAFLD (61% vs 23%; p=.006) and controls with NAFLD (61% vs 32%; p<.05). SHRI was a determinant of subclinical atherosclerosis in psoriasis (OR, 3.5; p=.01). In the United States cohort, (n=162 psoriasis participants who underwent positron emission tomography and coronary CT angiography), those with high hepatic F-FDG uptake had higher noncalcified (1.3 (0.49 mm) vs 1.0 (0.40 mm)), fibrofatty (0.23 (0.15 mm) vs 0.11 (0.087 mm)), and lipid rich necrotic core (4.3 (2.3 mm) vs 3.0 (1.7 mm)) coronary burden (all p<.001,). Hepatic F-FDG uptake associated with noncalcified (β=0.28; p<.001), fibrofatty (β=0.49; p<.001) and lipid rich necrotic core (β=0.28; p=.003) burden. These results demonstrate the downstream cardiovascular effects of subclinical liver disease in psoriasis.
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http://dx.doi.org/10.1016/j.jid.2021.05.034DOI Listing
July 2021

Diabetes Mellitus and Its Implications in Aortic Stenosis Patients.

Int J Mol Sci 2021 Jun 9;22(12). Epub 2021 Jun 9.

Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos (HNP), SESCAM, 45071 Toledo, Spain.

Aortic stenosis (AS) and diabetes mellitus (DM) are both progressive diseases that if left untreated, result in significant morbidity and mortality. Several studies revealed that the prevalence of DM is substantially higher in patients with AS and, thus, the progression from mild to severe AS is greater in those patients with DM. DM and common comorbidities associated with both diseases, DM and AS, increase patient management complexity and make aortic valve replacement the only effective treatment. For that reason, a better understanding of the pathogenesis underlying both these diseases and the relationships between them is necessary to design more appropriate preventive and therapeutic approaches. In this review, we provided an overview of the main aspects of the relationship between AS and DM, including common comorbidities and risk factors. We also discuss the established treatments/therapies in patients with AS and DM.
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http://dx.doi.org/10.3390/ijms22126212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227301PMC
June 2021

In vivo paradoxical embolism during monitorization of extracorporeal membrane oxygenation implantation.

Eur Heart J 2020 Dec 9. Epub 2020 Dec 9.

Cardiac Imaging Unit, Department of Cardiology, Hospital Universitario 12 de Octubre, Madrid, Spain.

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http://dx.doi.org/10.1093/eurheartj/ehaa1002DOI Listing
December 2020

Metabolic "ace of spades" in apical hypertrophic cardiomyopathy.

Rev Esp Cardiol (Engl Ed) 2021 03 7;74(3):264. Epub 2020 Nov 7.

Servicio de Cardiología, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain; Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Spain; Departamento de Medicina, Facultad de Medicina, Universidad Complutense, Madrid, Spain. Electronic address:

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http://dx.doi.org/10.1016/j.rec.2020.08.030DOI Listing
March 2021

Identification of a peripheral blood gene signature predicting aortic valve calcification.

Physiol Genomics 2020 12 12;52(12):563-574. Epub 2020 Oct 12.

Intercellular Signaling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.

Calcific aortic valve disease (CAVD) is a significant cause of illness and death worldwide. Identification of early predictive markers could help optimize patient management. RNA-sequencing was carried out on human fetal aortic valves at gestational , , and and on a case-control study with adult noncalcified and calcified bicuspid and tricuspid aortic valves. In dimension reduction and clustering analyses, diseased valves tended to cluster with fetal valves at rather than normal adult valves, suggesting that part of the disease program might be due to reiterated developmental processes. The analysis of groups of coregulated genes revealed predominant immune-metabolic signatures, including innate and adaptive immune responses involving lymphocyte T-cell metabolic adaptation. Cytokine and chemokine signaling, cell migration, and proliferation were all increased in CAVD, whereas oxidative phosphorylation and protein translation were decreased. Discrete immune-metabolic gene signatures were present at fetal stages and increased in adult controls, suggesting that these processes intensify throughout life and heighten in disease. Cellular stress response and neurodegeneration gene signatures were aberrantly expressed in CAVD, pointing to a mechanistic link between chronic inflammation and biological aging. Comparison of the valve RNA-sequencing data set with a case-control study of whole blood transcriptomes from asymptomatic individuals with early aortic valve calcification identified a highly predictive gene signature of CAVD and of moderate aortic valve calcification in overtly healthy individuals. These data deepen and broaden our understanding of the molecular basis of CAVD and identify a peripheral blood gene signature for the early detection of aortic valve calcification.
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http://dx.doi.org/10.1152/physiolgenomics.00034.2020DOI Listing
December 2020

Percutaneous closure of an atrial septal defect in a patient with Ebstein anomaly and right-to-left shunt.

Rev Port Cardiol (Engl Ed) 2020 Aug 3;39(8):475.e1-475.e3. Epub 2020 Aug 3.

Clinical Cardiology Unit, HM CIEC, Hospital Universitario HM Montepríncipe, Hospital Universitario HM Sanchinarro, Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain.

Ebstein anomaly is a congenital disease frequently associated with atrial septal defects, which can generate a right-to-left shunt, leading to systemic desaturation and right ventricular failure. We describe the case of a 68-year-old man with central cyanosis due to Ebstein anomaly and a patent foramen ovale. An atrial septal occluder was initially implanted after having performed prolonged test occlusion of the interatrial communication. In this case, device embolization occurred due to high right pressure. Percutaneous closure of atrial septal defects in the presence of a right-to-left shunt can offer a significant clinical improvement in selected cases. In patients with Ebstein anomaly, the implantation of atrial septal defect closure devices may be desirable, due to the larger size of the waist, which may provide better stability in the event of an increase in right pressure.
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http://dx.doi.org/10.1016/j.repc.2019.01.010DOI Listing
August 2020

Patient Management in Aortic Stenosis: Towards Precision Medicine Through Protein Analysis, Imaging and Diagnostic Tests.

J Clin Med 2020 Jul 28;9(8). Epub 2020 Jul 28.

Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos (HNP), SESCAM, 45071 Toledo, Spain.

Aortic stenosis is the most frequent valvular disease in developed countries. It progresses from mild fibrocalcific leaflet changes to a more severe leaflet calcification at the end stages of the disease. Unfortunately, symptoms of aortic stenosis are unspecific and only appear when it is too late, complicating patients' management. The global impact of aortic stenosis is increasing due to the growing elderly population. The disease supposes a great challenge because of the multiple comorbidities of these patients. Nowadays, the only effective treatment is valve replacement, which has a high cost in both social and economic terms. For that reason, it is crucial to find potential diagnostic, prognostic and therapeutic indicators that could help us to detect this disease in its earliest stages. In this article, we comprehensively review several key observations and translational studies related to protein markers that are promising for being implemented in the clinical field as well as a discussion about the role of precision medicine in aortic stenosis.
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http://dx.doi.org/10.3390/jcm9082421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463596PMC
July 2020

Multivessel spontaneous coronary artery dissection presenting in a patient with severe acute SARS-CoV-2 respiratory infection.

Eur Heart J 2020 May;41(32):3100-3101

Cardiology Department, Interventional Cardiology Unit, University Hospital 12 of October, Health Research Institute (i + 12), Madrid, Spain.

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http://dx.doi.org/10.1093/eurheartj/ehaa400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239194PMC
May 2020

Double-orifice mitral valve associated with multivalvular involvement: a new entity?

Eur Heart J 2020 08;41(29):2818

Cardiac Imaging Unit, Cardiology Department, University Hospital 12 of October, Health Research Institute (i + 12), Av. de Córdoba, s/n, 28041 Madrid, Spain.

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http://dx.doi.org/10.1093/eurheartj/ehaa240DOI Listing
August 2020

Diagnostic and Prognostic Value of Coronary Computed Tomography Angiography in Patients with Severe Calcification.

J Cardiovasc Transl Res 2021 02 1;14(1):131-139. Epub 2020 Apr 1.

Unidad de Imagen Cardiaca, Departamento de Cardiología, HM Hospitales-Centro Integral de Enfermedades Cardiovasculares HM CIEC, Madrid, Spain.

Our aim was to analyze its diagnostic and prognostic value in patients with high coronary calcium score (CCS). A total of 113 patients with CCS > 400 were included. Significant coronary artery disease (CAD) was defined as stenosis ≥ 50%. Invasive coronary angiography and major cardiovascular events were recorded. The CCS and heart rate during the acquisition were significantly lower in the diagnostic coronary computed tomography angiography (CCTA) group. The cut-off value of CCS to establish the diagnostic utility of CCTA was 878. The rate of cardiovascular events was 9.3%. The positive predictive value of CCTA to detect significant CAD was 73.5% and the negative predictive value for predicting cardiovascular events was 96%. In patients with high CCS, CCTA is useful to evaluate CAD, especially when the CCS is lower or equal to 878; moreover, the prognostic value of CCTA is better in patients where significant CAD has been ruled out.
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http://dx.doi.org/10.1007/s12265-020-09977-4DOI Listing
February 2021

Soluble ICAM 1 and VCAM 1 Blood Levels Alert on Subclinical Atherosclerosis in Non Smokers with Asymptomatic Metabolic Syndrome.

Arch Med Res 2019 02 31;50(2):20-28. Epub 2019 May 31.

George Washington Univ School of Medicine and Health Sciences, Washington DC, USA.

Background: Metabolic syndrome (MetS) is a heterogeneous clinical entity associated with insulin resistance, low-grade proinflammatory balance and impaired endothelial function, accelerating atherosclerosis. Atherosclerotic lesions worsen with age, smoking and co-morbidities, making it difficult to accurately diagnose the cardiovascular disease (CVD) risk.

Aim: We investigate the association between subclinical atherosclerosis and the presence of blood parameters related to adipocyte and vascular endothelial cell dysfunction, in non-smokers with MetS, under 60 and without previous CVD events.

Methods: Seventy-eight asymptomatic individuals (average 46.5 years, 69% male; 59 MetS and 19 controls) were studied prospectively. Subclinical CVD was defined by the presence of carotid plaque and/or carotid intima-media thickness (CIMT) > 0.9 in 2/3D ultrasound-studies, left ventricular hypertrophy (LVH) or high coronary calcium score (CCS). Multiplex immunoassay by Luminex xMAP was performed to measure plasma levels of adipokines and endothelial cell-derived molecules.

Results: Compared with controls, MetS patients had higher prevalence of carotid plaque (25 vs. 0%, p = 0.01), CIMT>0.9 (73 vs. 26%, p = 0.001) and higher CCS (69 vs. 5, p = 0.01), which were associated with a remarkable decrease in plasma Omentin levels and increase in sICAM-1, sVCAM-1 and PAI-1 (p <0.05). There was a statistically significant association between CIMT and sICAM-1 (OR: 14.57, 95% CI: 2.56-82.73, p <0.001), sVCAM-1 (OR:7.33, 95% CI: 1,58-33.96, p = 0.007) and PAI-1 (OR:7.80, 95% CI: 1.04-22.10, p = 0.036) in patients with carotid plaque and/or CIMT>0.9. Positive correlation between plaque volume and sICAM-1 levels was also detected (r = 0.40, p = 0.045).

Conclusions: We demonstrated that the increase of sICAM-1, sVCAM-1 and PAI-1, together with decrease of omentin-1 led to a proinflammatory imbalance pointing to the presence of subclinical atherosclerosis, and improving CVD risk stratification in non-smoking patients at early stage MetS beyond traditional scores.
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http://dx.doi.org/10.1016/j.arcmed.2019.05.003DOI Listing
February 2019

Frequency and Prognosis of Treated Hypertensive Patients According to Prior and New Blood Pressure Goals.

Hypertension 2019 07 28;74(1):130-136. Epub 2019 May 28.

Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid/IdiPAZ and CIBERESP, Spain (L.M.R., J.d.l.C., J.R.B.).

United States and European guidelines have recommended new treatment goals for office blood pressure (BP). We examined 9784 hypertensives of the Spanish Ambulatory BP Monitoring (ABPM) registry with office BP treated to the prior goal (<140/90 mm Hg); and evaluated the frequency and all-cause mortality of 4 BP strata depending on whether or not they attained more conservative or new office BP goal (130-139/80-89 and <130/80 mm Hg, respectively) and whether or not BP was controlled according to ABPM criteria in the European and US guidelines (24-hour ambulatory BP <130/80 and <125/75 mm Hg, respectively). Whether achieving or not the new office BP goal, the total-mortality risk during a 5-year follow-up was only significantly higher than the reference (normal office BP and ABPM) when 24-hour ambulatory BP was above goal (hazard ratio from multivariable Cox models was in the range of 2.4-2.9; P<0.001). The frequency of patients achieving the new office BP goal was 34.4%, and the frequencies of those not achieving the ABPM goal were 31.6% and 53.7% using the 130/80 or the 125/75 ABPM goal, respectively. Mean office systolic BP was 129 mm Hg for patients not achieving the ABPM goal. In hypertensive patients controlled under prior office BP goal, the frequency of those achieving new office BP goal <130/80 was high, suggesting this goal can be attained. In addition, patients had a higher mortality risk only when ABPM was above goal despite having mean office systolic BP under control, a condition that was also common.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.12921DOI Listing
July 2019

Genome-Wide Association Study-Driven Gene-Set Analyses, Genetic, and Functional Follow-Up Suggest GLIS1 as a Susceptibility Gene for Mitral Valve Prolapse.

Circ Genom Precis Med 2019 05;12(5):e002497

INSERM, UMR970, Paris Cardiovascular Research Center, France (M.Y., A.G., S.K., A.A.H., X.J., N.B.-N.).

Background Mitral valve prolapse (MVP) is a common heart valve disease, the most frequent indication for valve repair or replacement. MVP is characterized by excess extracellular matrix secretion and cellular disorganization, which leads to bulky valves that are unable to coapt correctly during ventricular systole resulting in mitral regurgitation, and it is associated with sudden cardiac death. Here we aim to characterize globally the biological mechanisms underlying genetic susceptibility to MVP to better characterize its triggering mechanisms. Methods We applied i-GSEA4GWAS and DEPICT, two pathway enrichment tools to MVP genome-wide association studies. We followed-up the association with MVP in an independent dataset of cases and controls. This research was conducted using the UK Biobank Resource. Immunohistochemistry staining for Glis1 (GLIS family zinc finger 1) was conducted in developing heart of mice. Knockdown of Glis1 using morpholinos was performed in zebrafish animals 72 hours postfertilization. Results We show that genes at risk loci are involved in biological functions relevant to actin filament organization, cytoskeleton biology, and cardiac development. The enrichment for positive regulation of transcription, cell proliferation, and migration motivated the follow-up of GLIS1, a transcription factor from the Krüppel-like zinc finger family. In combination with previously available data, we now report a genome-wide significant association with MVP (odds ratio, 1.20; P=4.36×10), indicating that Glis1 is expressed during embryonic development predominantly in nuclei of endothelial and interstitial cells of mitral valves in mouse. We also show that Glis1 knockdown causes atrioventricular regurgitation in developing hearts in zebrafish. Conclusions Our findings define globally molecular and cellular mechanisms underlying common genetic susceptibility to MVP and implicate established and unprecedented mechanisms. Through the GLIS1 association and function, we point at regulatory functions during cardiac development as common mechanisms to mitral valve degeneration.
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http://dx.doi.org/10.1161/CIRCGEN.119.002497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6532425PMC
May 2019

Fibroblast growth factor-23 promotes rhythm alterations and contractile dysfunction in adult ventricular cardiomyocytes.

Nephrol Dial Transplant 2019 11;34(11):1864-1875

Cardiorenal Translational Laboratory, Institute of Research i+12, Hospital Universitario 12 de Octubre, Madrid, Spain.

Background: Cardiac dysfunction and arrhythmia are common and onerous cardiovascular events in end-stage renal disease (ESRD) patients, especially those on dialysis. Fibroblast growth factor (FGF)-23 is a phosphate-regulating hormone whose levels dramatically increase as renal function declines. Beyond its role in phosphorus homeostasis, FGF-23 may elicit a direct effect on the heart. Whether FGF-23 modulates ventricular cardiac rhythm is unknown, prompting us to study its role on excitation-contraction (EC) coupling.

Methods: We examined FGF-23 in vitro actions on EC coupling in adult rat native ventricular cardiomyocytes using patch clamp and confocal microscopy and in vivo actions on cardiac rhythm using electrocardiogram.

Results: Compared with vehicle treatment, FGF-23 induced a significant decrease in rat cardiomyocyte contraction, L-type Ca2+ current, systolic Ca2+ transients and sarcoplasmic reticulum (SR) load and SR Ca2+-adenosine triphosphatase 2a pump activity. FGF-23 induced pro-arrhythmogenic activity in vitro and in vivo as automatic cardiomyocyte extracontractions and premature ventricular contractions. Diastolic spontaneous Ca2+ leak (sparks and waves) was significantly increased by FGF-23 via the calmodulin kinase type II (CaMKII)-dependent pathway related to hyperphosphorylation of ryanodine receptors at the CaMKII site Ser2814. Both contraction dysfunction and spontaneous pro-arrhythmic Ca2+ events induced by FGF-23 were blocked by soluble Klotho (sKlotho).

Conclusions: Our results show that FGF-23 reduces contractility and enhances arrhythmogenicity through intracellular Ca2+ mishandling. Blocking its actions on the heart by improving sKlotho bioavailability may enhance cardiac function and reduce arrhythmic events frequently observed in ESRD.
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http://dx.doi.org/10.1093/ndt/gfy392DOI Listing
November 2019

A 52-year-old woman with ventricular tachycardia.

Heart 2018 12 4;104(24):2025-2043. Epub 2018 Sep 4.

HM Hospitales-Centro Integral de Enfermedades Cardiovasculares HM-CIEC, Madrid, Spain.

Clinical Introduction: A 52-year-old woman with shortness of breath and palpitations was referred to a cardiologist. A 24-hour Holter demonstrated high density (37%) of ventricular premature beats (VPBs) and long runs of non-sustained (eventually sustained) monomorphic ventricular tachycardia (VT) with the same morphology as several VPBs detected in a 12-lead ECG (figure 1A). A transthoracic echocardiogram was performed, and the patient's evaluation was completed with a functional and gadolinium-enhanced cardiovascular MR (CMR) study (figure 1B,C) to assess structural heart disease. In a follow-up visit, an electrophysiological study (EPS) was performed to identify the origin of VPBs and VT (figure 1D).heartjnl;104/24/2025/F1F1F1Figure 1(A) A 12-lead ECG. (B) Cine CMR-SSFP (steady-state-free-precession) sequence on a three-chamber view. (C) Inversion-recovery gradient echo CMR pulse sequence for delayed enhancement assessment. (D) Three-dimensional electroanatomic voltage mapping of the left ventricular cavity (cranial left anterior oblique view). CMR, cardiovascular MR.

Question: What is the most likely cause of VPBs and VT?Idiopathic VT in the absence of structural heart disease.Bileaflet mitral valve prolapse (MVP).Dilated cardiomyopathy.Left ventricular non-compaction cardiomyopathy.Ischaemic cardiomyopathy.
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http://dx.doi.org/10.1136/heartjnl-2018-313347DOI Listing
December 2018

Mechanistic insights of the left ventricle structure and fibrosis in the arrhythmogenic mitral valve prolapse.

Glob Cardiol Sci Pract 2018 Mar 14;2018(1). Epub 2018 Mar 14.

Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.

Mitral valve prolapse (MVP) is a common and benign condition. However, some anatomic forms have been recently associated with life-threatening ventricular arrhythmias and sudden cardiac death. Imaging MVP holds the promise of individualized MVP risk assessment. Noninvasive imaging techniques available today are playing an increasingly important role in the diagnosis, prognosis and monitoring of MVP. In this article, we will review the current evidence on arrhythmogenic MVP, with special focus on the utility of echocardiography and CMR for identifying benign and "malignant" forms of MVP. The clinical relevance of this manuscript lies in the value of imaging technology to improve MVP risk prediction, including those arrhythmic-MVP cases with a higher risk of sudden cardiac death.
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http://dx.doi.org/10.21542/gcsp.2018.4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857061PMC
March 2018

The key is in the air: transthoracic echocardiogram leading to diagnose emphysematous gastritis.

Eur Heart J Cardiovasc Imaging 2018 05;19(5):585

Cardiology Department, Hospital Universitario 12 de Octubre, Cordoba Avenue, 28041 Madrid, Spain.

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http://dx.doi.org/10.1093/ehjci/jey002DOI Listing
May 2018

Atrial Infarction and Ischemic Mitral Regurgitation Contribute to Post-MI Remodeling of the Left Atrium.

J Am Coll Cardiol 2017 Dec;70(23):2878-2889

Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; CIBER de enfermedades CardioVasculares, Madrid, Spain; Cardiology Department, IIS-Fundación Jiménez Díaz Hospital, Madrid, Spain. Electronic address:

Background: Left atrial (LA) remodeling after an acute myocardial infarction (MI) is poorly characterized regarding its determinants or its effect on ischemic mitral regurgitation (MR) development.

Objectives: The purpose of this study was: 1) to compare LA structural remodeling in experimental MI swine models recapitulating the effects of left ventricular (LV) dysfunction, ischemic MR, and left atrial infarction (LAI); and 2) to analyze how LA remodeling influences ischemic MR development.

Methods: Three models of MI were generated: 1) proximal left circumflex (LCx) coronary artery occlusion involving the LA branch (LAI group); 2) proximal LCx occlusion not involving the LA branch (LCx group); and 3) left anterior descending (LAD) occlusion (LAD group). Serial cardiac magnetic resonance scans were performed to define LA and LV remodeling and ischemic MR, and were correlated with histology.

Results: Occlusion of the LA branch (LAI group) induced a greater degree of LA dilation at 1 and 8 weeks post-MI than the LCx and LAD groups, along with early and severe impairment of LA function. In the LCx and LAD groups, LA dysfunction was less pronounced and not consistent. Development of ischemic MR was more pronounced in the LAI group than in the LCx group. Histology confirmed atrial infarction with extensive fibrosis in the LAI group and interstitial fibrosis in the LCx group. In the LAD group, LA remodeling was not observed by cardiac magnetic resonance or histology.

Conclusions: We provide the first experimental evidence of the deleterious effect of acute LAI on atrial structural remodeling, characterized by early LA dilation, dysfunction, and fibrosis, and early occurrence of ischemic MR.
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http://dx.doi.org/10.1016/j.jacc.2017.10.013DOI Listing
December 2017

In-frame Variants in FLNA Proximal Rod 1 Domain Associate With a Predominant Cardiac Valvular Phenotype.

Rev Esp Cardiol (Engl Ed) 2018 Jul 14;71(7):545-552. Epub 2017 Nov 14.

Instituto de Genética Médica y Molecular (INGEMM), Instituto de Investigación del Hospital Universitario La Paz (IdiPAZ), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Unidad de Genética Clínica, Hospital Universitario HM Montepríncipe, Madrid, Spain.

Introduction And Objectives: X-linked cardiac valvular dysplasia is a rare form of male-specific congenital heart defect mainly characterized by myxomatous degeneration of the atrioventricular valves with variable hemodynamic consequences. It is caused by genetic defects in FLNA-encoded filamin A, a widely expressed actin-binding protein that regulates cytoskeleton organization. Filamin A loss of function has also been associated with often concurring neurologic and connective tissue manifestations, with mutations in the first half of the Rod 1 domain apparently expressing the full cardiac phenotype. We contribute to previous genotype-phenotype correlations with a multidisciplinary approach in a newly-described family.

Methods: Cardiologic, dysmorphologic, and genetic evaluation of available members were complemented with transcriptional and X-chromosome inactivation studies.

Results: A novel FLNA mutation c.1066-3C>G cosegregated with a male-expressed, apparently isolated, cardiac phenotype with no skewed X-inactivation pattern in female carriers. This variant was shown to result in an in-frame deletion of 8 amino acid residues near the N-terminal region of the protein.

Conclusions: A nonimprinted, partial loss of function of filamin A proximal Rod 1 domain seems to be the pathogenetic mechanism of cardiac valvular dysplasia, with some cases occasionally expressing associated extracardiac manifestations.
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http://dx.doi.org/10.1016/j.rec.2017.10.013DOI Listing
July 2018

Outcomes of patients at estimated low surgical risk undergoing transcatheter aortic valve implantation with balloon-expandable prostheses.

Cardiovasc Revasc Med 2018 04 30;19(3 Pt A):251-256. Epub 2017 Aug 30.

Cardiology, Hospital Universitario Madrid Montepríncipe.

Introduction And Objectives: Transcatheter aortic-valve implantation (TAVI) is an accepted treatment for patients with severe aortic stenosis and high surgical risk. However, there is lack in data about TAVI in low-risk patients that are already being treated with this therapy in some clinical contexts.

Methods: A retrospective analysis of patients treated with transfemoral TAVI using Edwards Sapien prosthesis in one center was performed, classifying the patients into three groups according to the surgical risk (high/intermediate/low risk for STS score>8/4-8/<4). Clinical characteristics, procedure and follow-up outcomes were collected, comparing the results between low and high surgical risk groups.

Results: 89 TAVIs using Edwards balloon expandable prosthesis were performed (9 Sapien XT and 80 Sapien 3 valves were implanted). 40 patients (45%) presented a STS score<4, while 33 (37%) had a STS>8. Low-risk patients were significantly younger and had lower rates of coronary artery disease, peripheral vascular disease, pulmonary lung disease and atrial fibrillation. There were no significant differences in most of the technical variables of the procedure, apart from vascular complications and complete left bundle branch block after valve implant, which were higher in the group with STS>8. Patients of low risk presented shorter hospital stay (2,91±1,6, vs 4,8±3,9 days), with lower rates of mortality at mid- and long follow-up (death from any cause 15,2% vs 0%, p 0,04).

Conclusions: TAVI in low-risk patients is safe and associated with better outcome at mid and long-term follow-up compared to high-risk patients.
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http://dx.doi.org/10.1016/j.carrev.2017.08.012DOI Listing
April 2018

Transcatheter Aortic Valve Implantation in Patients With Arterial Peripheral Vascular Disease.

Rev Esp Cardiol (Engl Ed) 2017 06 22;70(6):510-512. Epub 2016 Nov 22.

Servicio de Cardiología, Hospital Universitario Madrid Montepríncipe, Madrid, Spain.

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http://dx.doi.org/10.1016/j.rec.2016.10.008DOI Listing
June 2017

Two-Year Follow Up After Surgical Versus Percutaneous Paravalvular Leak Closure: A Non-Randomized Analysis.

Catheter Cardiovasc Interv 2016 Oct 4;88(4):626-634. Epub 2016 Mar 4.

Instituto De Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Departamento De Medicina, Madrid, Spain.

Background: Percutaneous closure of paravalvular leak (PVL) has emerged as an alternative treatment. Predictors of survival and procedural success are unknown.

Objectives: To review our experience in the treatment of PVL and evaluate efficacy, mortality, predictors of success, and outcomes.

Methods: Retrospective review of percutaneous PVL procedures between years 2008 and 2014. Survival and results were compared with a control cohort of surgical patients.

Results: Percutaneous closure was attempted in 51 patients. The surgical group had 36 patients. Defects were perimitral in 67 patients (77%). Mean follow-up (FU) was 784.5 days. After propensity score analysis in-hospital mortality was higher in the surgical group (30.6% vs. 9.8%, OR 6, P 0.01). Clinical improvement was higher in the percutaneous group (71.4% vs. 36.4%, P 0.002). Multivariate analysis showed normal creatinine (OR 15, P < 0.001) as independent predictor of clinical improvement. For the composite end-point of all-cause mortality or readmission, older age (OR 10.7, P 0.001), renal failure, (OR 18, P < 0.01), poor functional class and the absence of clinical improvement (OR 3.9, P < 0.001) were related with a higher risk. There were no differences in survival free from the composite end-point according to the treatment received (surgical or percutaneous).

Conclusion: Percutaneous PVL closure has a reasonable rate of success and low complication rates, and results compare favorably with surgical treatment. Older patients and those with poor functional class or renal failure (RF) showed a worse prognosis even after a successful closure. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ccd.26459DOI Listing
October 2016

Hybrid F-FDG PET/MRI in Ischemic Cardiomyopathy.

Rev Esp Cardiol (Engl Ed) 2017 May 13;70(5):393. Epub 2016 Oct 13.

Unidad de Imagen Cardiaca, Departamento de Cardiología, Hospital Universitario HM Montepríncipe-CIEC/Hospital Universitario HM Puerta del Sur, Madrid, Spain; Área de Fisiopatología Vascular, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.

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http://dx.doi.org/10.1016/j.rec.2016.09.005DOI Listing
May 2017

Mitral valve disease--morphology and mechanisms.

Nat Rev Cardiol 2015 Dec 20;12(12):689-710. Epub 2015 Oct 20.

Aix-Marseille University, INSERM UMR 910, Marseille, France.

Mitral valve disease is a frequent cause of heart failure and death. Emerging evidence indicates that the mitral valve is not a passive structure, but--even in adult life--remains dynamic and accessible for treatment. This concept motivates efforts to reduce the clinical progression of mitral valve disease through early detection and modification of underlying mechanisms. Discoveries of genetic mutations causing mitral valve elongation and prolapse have revealed that growth factor signalling and cell migration pathways are regulated by structural molecules in ways that can be modified to limit progression from developmental defects to valve degeneration with clinical complications. Mitral valve enlargement can determine left ventricular outflow tract obstruction in hypertrophic cardiomyopathy, and might be stimulated by potentially modifiable biological valvular-ventricular interactions. Mitral valve plasticity also allows adaptive growth in response to ventricular remodelling. However, adverse cellular and mechanobiological processes create relative leaflet deficiency in the ischaemic setting, leading to mitral regurgitation with increased heart failure and mortality. Our approach, which bridges clinicians and basic scientists, enables the correlation of observed disease with cellular and molecular mechanisms, leading to the discovery of new opportunities for improving the natural history of mitral valve disease.
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http://dx.doi.org/10.1038/nrcardio.2015.161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804623PMC
December 2015

Congenital atresia of the left main coronary artery in an adult: A rare anomaly with an unfavorable prognosis. Review of the literature.

Cardiovasc Revasc Med 2015 Dec 21;16(8):498-502. Epub 2015 Aug 21.

Hospital Universitario Madrid Montepríncipe.

Congenital atresia of the left main coronary artery (LMCA) is one of the rarest congenital anomalies, which may have an unfavorable prognosis leading to myocardial ischemia, ventricle dysfunction or even sudden cardiac death. There are 34 cases of LMCA in adults reported in the literature, most of them successfully treated with coronary revascularization. We report the case of an adult with LMCA who presented with terminal heart failure that required biventricular assistance and heart transplant.
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http://dx.doi.org/10.1016/j.carrev.2015.08.006DOI Listing
December 2015

Genetic association analyses highlight biological pathways underlying mitral valve prolapse.

Nat Genet 2015 Oct 24;47(10):1206-11. Epub 2015 Aug 24.

Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA.

Nonsyndromic mitral valve prolapse (MVP) is a common degenerative cardiac valvulopathy of unknown etiology that predisposes to mitral regurgitation, heart failure and sudden death. Previous family and pathophysiological studies suggest a complex pattern of inheritance. We performed a meta-analysis of 2 genome-wide association studies in 1,412 MVP cases and 2,439 controls. We identified 6 loci, which we replicated in 1,422 cases and 6,779 controls, and provide functional evidence for candidate genes. We highlight LMCD1 (LIM and cysteine-rich domains 1), which encodes a transcription factor and for which morpholino knockdown of the ortholog in zebrafish resulted in atrioventricular valve regurgitation. A similar zebrafish phenotype was obtained with knockdown of the ortholog of TNS1, which encodes tensin 1, a focal adhesion protein involved in cytoskeleton organization. We also showed expression of tensin 1 during valve morphogenesis and describe enlarged posterior mitral leaflets in Tns1(-/-) mice. This study identifies the first risk loci for MVP and suggests new mechanisms involved in mitral valve regurgitation, the most common indication for mitral valve repair.
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http://dx.doi.org/10.1038/ng.3383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773907PMC
October 2015

Mutations in DCHS1 cause mitral valve prolapse.

Nature 2015 Sep 10;525(7567):109-13. Epub 2015 Aug 10.

National Heart and Lung Institute, Harefield, Heart Science Centre, Imperial College London, London SW7 2AZ, UK.

Mitral valve prolapse (MVP) is a common cardiac valve disease that affects nearly 1 in 40 individuals. It can manifest as mitral regurgitation and is the leading indication for mitral valve surgery. Despite a clear heritable component, the genetic aetiology leading to non-syndromic MVP has remained elusive. Four affected individuals from a large multigenerational family segregating non-syndromic MVP underwent capture sequencing of the linked interval on chromosome 11. We report a missense mutation in the DCHS1 gene, the human homologue of the Drosophila cell polarity gene dachsous (ds), that segregates with MVP in the family. Morpholino knockdown of the zebrafish homologue dachsous1b resulted in a cardiac atrioventricular canal defect that could be rescued by wild-type human DCHS1, but not by DCHS1 messenger RNA with the familial mutation. Further genetic studies identified two additional families in which a second deleterious DCHS1 mutation segregates with MVP. Both DCHS1 mutations reduce protein stability as demonstrated in zebrafish, cultured cells and, notably, in mitral valve interstitial cells (MVICs) obtained during mitral valve repair surgery of a proband. Dchs1(+/-) mice had prolapse of thickened mitral leaflets, which could be traced back to developmental errors in valve morphogenesis. DCHS1 deficiency in MVP patient MVICs, as well as in Dchs1(+/-) mouse MVICs, result in altered migration and cellular patterning, supporting these processes as aetiological underpinnings for the disease. Understanding the role of DCHS1 in mitral valve development and MVP pathogenesis holds potential for therapeutic insights for this very common disease.
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http://dx.doi.org/10.1038/nature14670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720389PMC
September 2015

Efficacy of polymer injection for ischemic mitral regurgitation: persistent reduction of mitral regurgitation and attenuation of left ventricular remodeling.

JACC Cardiovasc Interv 2015 Feb 14;8(2):355-363. Epub 2015 Jan 14.

Cardiac Ultrasound Laboratory, Massachusetts General Hospital, Boston, Massachusetts. Electronic address:

Objectives: The aim of this study was to examine the chronic effects of polyvinyl-alcohol (PVA) injection on mitral regurgitation (MR) reduction, mitral valve geometry, and left ventricular (LV) remodeling in a chronic ischemic MR sheep model.

Background: Previous studies have demonstrated acute efficacy of PVA hydrogel polymer injection into infarcted myocardium underlying the papillary muscle to relieve MR by papillary muscle repositioning. However, the chronic efficacy of PVA injection in the chronic infarction setting remains unclear.

Methods: Sixteen sheep developed chronic MR 8 weeks after induced inferoposterior myocardial infarction. Ten consecutive sheep underwent PVA injection (PVA group) and 6 sheep served as control subjects with saline injection. Epicardial 2-/3-dimensional echocardiography was performed at the baseline, chronic MR (pre-injection), and sacrifice (8 weeks after injection) stages.

Results: Both groups were comparable at the baseline and chronic MR stages. At sacrifice, MR decreased from moderate to trace or mild (vena contracta: 0.17 ± 0.08 cm vs. 0.56 ± 0.10 cm, p < 0.001) in the PVA group but progressed to moderate to severe in the control group. End-systolic and -diastolic volumes remained stable in the PVA group but increased significantly in the control group (both p < 0.05). At sacrifice, compared with the control group, the PVA group had significantly less left ventricular remodeling (end-systolic volume: 41.1 ± 10.4 ml vs. 55.9 ± 12.4 ml, p < 0.05), lower MR severity (vena contracta: 0.17 ± 0.08 cm vs. 0.60 ± 0.14 cm, p < 0.01), and favorable changes in mitral valve geometry.

Conclusions: Polymer injection in a chronic ischemic MR model results in persistent reduction of MR and attenuation of continued left ventricular remodeling over 8 weeks of follow-up.
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http://dx.doi.org/10.1016/j.jcin.2014.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645299PMC
February 2015

Initial experience with the low-profile percutaneous aortic valve SAPIEN 3.

Rev Esp Cardiol (Engl Ed) 2014 Nov 27;67(11):953-4. Epub 2014 Sep 27.

Servicio de Cardiología, Hospital Moncloa, Madrid, Spain.

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http://dx.doi.org/10.1016/j.rec.2014.04.014DOI Listing
November 2014

How to grade mitral regurgitation: an integrative approach.

Cardiol Clin 2013 May;31(2):169-75

Department of Cardiology, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, Madrid 28007, Spain.

Evaluation of mitral regurgitation (MR) severity remains complex and challenging. An integrative approach to grading MR is recommended. The use of multiple Doppler methods should be used to help discriminate between grades of severity. Importantly, MR severity should always be considered in the context of clinical data. The emerging inclusion of 3-dimensional echocardiography may provide complementary data for MR quantification and better anatomic and pathophysiological detail of the mitral valve. This article summarizes recommendations for MR assessment and highlights the importance of an integrated approach, using anatomic information as well as qualitative and quantitative Doppler measures.
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http://dx.doi.org/10.1016/j.ccl.2013.04.002DOI Listing
May 2013
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