Juan Robledo-Carmona

Hereditary patterns of bicuspid aortic valve in a hundred families.

BACKGROUND To study the following characteristics of bicuspid aortic valves (BAVs): 1) the recurrence rate in our population, 2) patterns of hereditary transmission in different BAV morphologies and 3) the aortic dimensions of BAVs in first-degree relatives (FDRs). METHODS A cross-sectional, prospective study of 100 consecutive families of BAV patients attending a university hospital. The following aortic valve morphologies were analysed and categorised: fusion of the right and left coronary cusps (BAV type A), right and noncoronary cusps (type B) and of the left and noncoronary cusps (type C). RESULTS There were 553 subjects studied, 100 cases with a BAV (46.8±15 years, 66% male, type 67% A, 32% B and 1% C; 42% with aortic dilatation), 348 FDRs (44.8% male), and 105 healthy control subjects (50% male). We detected 16 BAVs among 348 FDRs. The recurrence rates were 15% for families, 4.6% for FDRs, 7.05% in men and 2.60% in women. The morphologic concordance in family members was 68.8%. The aortic dimensions in 270 adult FDRs with a tricuspid aortic valve were significantly smaller compared with BAV patients (sinus index diameter 1.60±0.19 cm/m(2) vs. 1.82±0.29 cm/m(2), p<0.001; tubular index diameter 1.51±0.23 cm/m(2) vs. 2.00±0.45 cm/m(2), p<0.001) and similar to 103 control subjects(sinus index diameter 1.60±0.19 cm/m(2) vs. 1.59±0.17 cm/m(2), p=0.600 and tubular index diameter 1.51±0.23 cm/m(2) vs. 1.53±0.18 cm/m(2), p=0.519). CONCLUSIONS In our population, the BAV recurrence rate in FDRs was low (4.6%). The hereditary transmission of morphologic BAV types seems by chance, and the aortic dimensions in tricuspid FDRs are normal.

Selection of Reference Genes for Quantitative Real Time PCR (qPCR) Assays in Tissue from Human Ascending Aorta

Dilatation of the ascending aorta (AAD) is a prevalent aortopathy that occurs frequently associated with bicuspid aortic valve (BAV), the most common human congenital cardiac malformation. The molecular mechanisms leading to AAD associated with BAV are still poorly understood. The search for differentially expressed genes in diseased tissue by quantitative real-time PCR (qPCR) is an invaluable tool to fill this gap. However, studies dedicated to identify reference genes necessary for normalization of mRNA expression in aortic tissue are scarce. In this report, we evaluate the qPCR expression of six candidate reference genes in tissue from the ascending aorta of 52 patients with a variety of clinical and demographic characteristics, normal and dilated aortas, and different morphologies of the aortic valve (normal aorta and normal valve n = 30; dilated aorta and normal valve n = 10; normal aorta and BAV n = 4; dilated aorta and BAV n = 8). The expression stability of the candidate reference genes was determined with three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable genes for the three algorithms employed were CDKN1β, POLR2A and CASC3, independently of the structure of the aorta and the valve morphology. In conclusion, we propose the use of these three genes as reference genes for mRNA expression analysis in human ascending aorta. However, we suggest searching for specific reference genes when conducting qPCR experiments with new cohort of samples.

Long-term prognostic value of late gadolinium enhancement in a cohort of patients with nonischemic dilated cardiomyopathy.

Thepresenceoflategadoliniumenhancement(LGE)incardiacmag-netic resonance (CMR), that enables quantification of myocardialfibro-sis[1],iscommoninpatientswithnonischemicdilatedcardiomyopathy(NIDC). LGE has been related to adverse clinical outcomes in patientswith NIDC, mainly in those with idiopathic dilated cardiomyopathy[1,2]. This study pretends to assess the long-term prognostic signifi-cance of LGE in an unselected population of patients with NIDC. Everyunderlying possible cause was included.Weperformed aretrospective cohortstudyinwhich64consecutiveoutpatients with heart failure secondary to NIDC were included. Allunderwent a CMR between August 2005 and November 2011. Thepresence and location of LGE were evaluated.Diagnosis was established according to the World HealthOrganization/International Society and Federation of Cardiologysdefinition [3]. None of the patients presented previous history ofsignificant valvular disease, hypertrophic cardiomyopathy, restrictivecardiomyopathy, congenital heart disease, or coronary artery disease.PatientsunderwentCMRjustafterthediagnosisofNIDCtocompletethe diagnostic evaluation. Exclusion criteria were: cardiac pacemaker/implantable cardioverter defibrillator (ICD)/cardiac resynchronizationtherapy, renal insufficiency and severe obesity or claustrophobia.Patientswerefollowedviaclinicalvisits.Theprimaryoutcomewasacomposite endpoint of three events: cardiac death, hospitalization forheart failure and appropriate ICD firing. ICD devices were implanted insome patients after they underwent CMR.CMRimagingwasperformedona1.5Teslascanner(PhilipsMRSys-tem Achieva Release 2.6.3.7). Delayed contrast-enhanced images wereacquired 10 min after intravenous administration of 0.2 mmol/kg ofgadolinium-diethylenetriaminepentaacetate, using inversion-recoveryfast gradient-echo pulse sequences in sequential short- and long-axisslices of the left ventricle.Allstudies were analyzedby aradiologistand acardiologist usinga workstation (Extended MR Work Space 2.6.2.4.). The presence andlocation of LGE were visually assessed.Qualitativevariableswereexpressedaspercentagesandquantitativeasmean±SD.Qualitativevariableswerecomparedwiththeχ

Increased blood levels of transforming growth factor β in patients with aortic dilatation

OBJECTIVES Recent studies have shown that patients with syndromic thoracic aortic aneurysm, particularly patients with bicuspid aortic valve, have increased blood levels of transforming growth factor β1 (TGF-β1), indicating this molecule as a prognostic biomarker. However, it is not known whether TGF-β1 is also elevated in the blood of patients with tricuspid aortic valve and aortic dilatation. METHODS We analysed the plasma levels of TGF-β1 in 52 patients with tricuspid or bicuspid aortic valve and with normal or dilated ascending aorta who underwent cardiac surgery in our hospital. RESULTS TGF-β1 blood level was significantly increased two-fold in patients with tricuspid aortic valve and dilated aorta compared to patients with tricuspid aortic valve and normal aorta. CONCLUSIONS Our results suggest that TGF-β1 blood levels may serve as a prognostic biomarker for patients with syndromic and non-syndromic thoracic aortic aneurysm. Further studies with larger cohorts of patients should be performed to confirm these results.

Fibrillin 2 is upregulated in the ascending aorta of patients with bicuspid aortic valve

OBJECTIVES: Bicuspid aortic valve (BAV) is the most prevalent congenital cardiac malformation, frequently associated with aortic dilatation (AD). The molecular mechanisms involved in AD and its aetiological link with BAV formation are poorly understood. Altered fibrillin-1 (FBN1) and metalloprotease-2, -9 (MMP2,9) protein activities have been suggested to be involved in BAV aortopathy. In addition, FBN2 participates in embryonic valve formation, but its possible involvement in BAV-associated AD has never been explored. In this report, we evaluate the expression levels of MMP2,9 and FBN1,2 in the ascending aorta of patients with normal or dilated aortas and with tricuspid aortic valve (TAV) or BAV, using appropriate tissue-specific reference genes. METHODS: Gene expression was quantified by real-time quantitative polymerase chain reaction in 52 patients, using one or three reference genes previously validated in the same patient population. RESULTS: FBN2 expression was significantly increased in the aortas of patients with BAV compared with individuals with TAV (0.178 ± 0.042 vs 0.096 ± 0.021, P = 0.015), whereas differences in FBN1 did not reach statistical significance (1.946 ± 0.228 vs 1.430 ± 0.114, P = 0.090). When four groups of samples were considered, FBN2 expression was significantly higher in patients with BAV and AD compared with patients with TAV and AD (0.164 ± 0.035 vs 0.074 ± 0.027, P = 0.040). No significant differences were found when FBN1/FBN2 ratio, and MMP2 and MMP9 expression levels were analysed. No linear relationship between aortic diameter and gene expression levels were found. CONCLUSIONS: BAV patients have an increased FBN (especially FBN2) gene expression level in the ascending aorta, irrespective of dilatation, whereas MMP expression does not change significantly. These results add a new piece of information to the pathophysiology of BAV disease and point to FBN2 as a new molecular player.

Clinical and echocardiographic course in tako­tsubo cardiomyopathy: Long­term follow­up from a multicenter study

OBJECTIVES To jointly describe clinical characteristics, ECG and echocardiographic findings, and adverse cardiovascular events in patients with tako-tsubo cardiomyopathy (TC) in the long-term. METHODS Longitudinal multicenter study including retrospective analysis of clinical and ECG data, and follow-up evaluation with clinical interview, electrocardiogram and echocardiogram. RESULTS Data from 66 cases of TC were available for analysis of clinical and adverse cardiovascular events, and 56 of them completed the follow-up visit including electrocardiogram and echocardiogram. Most patients (97%) were asymptomatic or oligosymptomatic (NYHA I [58%] or II [39%], respectively) at follow-up (median time: 3.7 [1.8-6.6] years). The vast majority of individual QRS complex and repolarization abnormalities had disappeared (87% with no ECG abnormalities at follow-up). On echocardiography, left ventricular ejection fraction was ≥50% in all patients (mean: 63±6%). Wall motion abnormalities were observed in 4 patients (7%; 3 with apical wall motion abnormalities and 1 with mild global hypokinesia). Long-term outcomes were as follows: 4 deaths (6%), 2 cardiovascular and 2 non-cardiovascular; no atrial fibrillation development; no stroke events; 5 acute recurrence events of TC (8%). Globally, 57 patients (86%) had a clinical course free from adverse cardiovascular events. CONCLUSIONS After a long period following the admission event, patients discharged from TC remain asymptomatic or minimally symptomatic, and feature a low prevalence of both ECG and left ventricular wall motion abnormalities; moreover, the latter lead to a very mild impairment of ejection fraction. Among cardiovascular adverse events, recurrence of the TC event appears to play the most significant role.

Reply to the letter “Prognostic value of late gadolinium enhancement in cardiomyopathy: Causative risk factor or surrogate marker?”

a Seccion de Cardiologia, Unidad de Medicina Interna, Hospital de Poniente, Carretera de Almerimar s/n, 04700 El Ejido, Almeria, Spain b Area del Corazon, Hospital Universitario Virgen de la Victoria, Campus Teatinos s/n, 29010 Malaga, Spain c Seccion de Cardiologia, Unidad de Medicina Interna, Fundacion Hospital Calahorra, Carretera de Logrono s/n, 26500 Calahorra, La Rioja, Spain d Unidad de Cardiologia, Hospital Parque San Antonio, Avenida Pintor Joaquin Sorolla n°2, 29016, Malaga, Spain

Endocarditis infecciosa sobre válvula aórtica bicúspide: características clínicas, complicaciones y pronóstico

INTRODUCTION Bicuspid aortic valve (BAV) is the most frequent congenital cardiac disease. It is associated to a higher risk of cardiovascular complications, including infective endocarditis (IE). METHODS Retrospective, observational and single centre study that included all patients with IE diagnosed between 1996 and 2014. An analysis was made of the epidemiological, clinical, microbiological and echocardiographic data, complications during hospital admission, need for surgery, in-hospital mortality, and 1-year follow-up. Cases with endocarditis on prosthetic valves or other locations were excluded, as well as those for which the aortic valve morphology had not been accurately defined. A comparative statistical analysis was performed between BAV and tricuspid (TAV). RESULTS Of a total of 328 cases with IE, 118 (35.67%) were on aortic valve, with 18 (16.22%) of them being BAV. The BAV cases were younger than TAV (51±19.06 vs. 60.83±15.73 years, P=.021) and they had less comorbidity (Charlson 0.67±0.77 vs. 1.44±1.64, P=.03).). There was a higher tendency of Staphylococcal origin (38.9 vs. 21.5%, P=.137), and 55.6% showed peri-valvular complications (TAV 16.1%, P=.001), in particular, abscesses (38.9 vs.16.1%, P=.047). BAV was the only predictive factor of peri-valvular complications (OR 7.87, 95% CI; 2.38-26.64, P=.001). Patients with BAV had more surgery during their admission (83.3 vs. 44.1%, P=.004), had less in-hospital mortality, with no statistical significance (5.6 vs. 25.8%, P=.069), and 1-year survival was significantly superior (93.8 vs 69.3%, P=.048). CONCLUSIONS Patients with IE on BAV are young, with low comorbidity. They frequently present with peri-valvular complications and they often require early surgery. Compared to TAV cases, in-hospital mortality is lower and 1-year survival is significantly higher.

Elevation of circulating progenitor cells in patients with acute myocarditis

Guillermo Isasti , Jose Manuel Garcia-Pinilla , Manuel F. Jimenez-Navarro ⁎, Juan Jose Gomez-Doblas , Fernando Cabrera-Bueno , Noela Rodriguez-Losada , Juan Robledo-Carmona , Eduardo de Teresa-Galvan a,1 a UGC del Corazon, Instituto de Biomedicina de Malaga (IBIMA), Hospital Universitario Virgen de la Victoria, Campus Teatinos s/n, Malaga, Spain b Laboratorio de Medicina Regenerativa, Instituto de Biomedicina de Malaga (IBIMA), Hospital Regional Carlos Haya, Avda. Carlos Haya s/n, Malaga, Spain