Fernando Carrasco-Chinchilla

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.

Initial experience of percutaneous treatment of mitral regurgitation with MitraClip® therapy in Spain.

INTRODUCTION AND OBJECTIVES Symptomatic mitral regurgitation has an unfavorable prognosis unless treated by surgery. However, the European registry of valvular heart disease reports that 49% of patients with this condition do not undergo surgery. Percutaneous treatment of mitral regurgitation with MitraClip® has been proved a safe, efficient adjunct to medical treatment in patients with this profile. The objective of the present study is to describe initial experience of MitraClip® therapy in Spain. METHODS Retrospective observational study including all patients treated between November 2011 and July 2013 at the 4 Spanish hospitals recording the highest numbers of implantations. RESULTS A total of 62 patients (77.4% men) were treated, mainly for restrictive functional mitral regurgitation (85.4%) of grade III (37%) or grade IV (63%), mean (standard deviation) ejection fraction 36% (14%), and New York Heart Association functional class III (37%) or IV (63%). Device implantation was successful in 98% of the patients. At 1 year, 81.2% had mitral regurgitation ≤ 2 and 90.9% were in New York Heart Association functional class ≤ II. One periprocedural death occurred (sepsis at 20 days post-implantation) and another 3 patients died during follow-up (mean, 9.1 months). Two patients needed a second implantation due to partial dehiscence of the first device and 2 others underwent heart transplantation. CONCLUSIONS In Spain, MitraClip® therapy has principally been aimed at patients with functional mitral regurgitation, significant systolic ventricular dysfunction, and high surgical risk. It is considered a safe alternative treatment, which can reduce mitral regurgitation and improve functional capacity.

Remote Ischemic Postconditioning: Does It Protect against Ischemic Damage in Percutaneous Coronary Revascularization? Justification and Design of a Randomized Placebo-Controlled Clinical Trial

Objective: Myocardial damage that is associated with percutaneous coronary intervention (PCI) partially affects the results of the procedure, and is related to medium-term cardiovascular death. Remote postischemic conditioning might reduce the myocardial lesions that are associated with PCI, but perhaps less so in diabetics. The aim of this study was to evaluate the protective effect of remote postischemic conditioning in patients undergoing elective PCI for stable angina or non-ST elevation acute coronary syndrome with troponin <1 ng/ml at the time of randomization. Methods: This randomized single-blinded single-center clinical trial involved 320 patients undergoing elective PCI who were randomized to either receive three 5-min cycles of ischemia by inflation of a cuff on the non-dominant arm to 200 mm Hg (remote postischemic conditioning) or to placebo (uninflated cuff). The primary outcome variable was the maximum increase in troponin in the first 24 h. The secondary outcome variable was readmission due to heart failure or cardiovascular mortality after 1 year of follow-up. In addition, a diabetic population was studied. Conclusions: This clinical trial evaluated the possible reduction in intervention-related myocardial damage that was attributable to remote postischemic conditioning.

Expression of epicardial adipose tissue thermogenic genes in patients with reduced and preserved ejection fraction heart failure

Epicardial adipose tissue has been proposed to participate in the pathogenesis of heart failure. The aim of our study was to assess the expression of thermogenic genes (Uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), and PR-domain-missing 16 (PRDM16) in epicardial adipose tissue in patients with heart failure, stablishing the difference according to left ventricular ejection fraction (reduced or preserved). Among the 75 patients in our study, 42.7% (n=32) had reduced left ventricular ejection fraction. UCP1, PGC1α and PRDM16 mRNA in EAT were significantly lower in patients with reduced left ventricular ejection fraction. Multiple regression analysis showed that age, male gender, body max index, presence of obesity, type-2-diabetes mellitus, hypertension and coronary artery disease and left ventricular ejection fraction were associated with the expression levels of UCP1, PGC1α and PRDM16 mRNA. Thermogenic genes expressions in epicardial adipose tissue (UCP1: OR 0.617, 95%CI 0.103-0.989, p=0.042; PGC1α: OR 0.416, 95%CI 0.171-0.912, p=0.031; PRDM16: OR 0.643, 95%CI 0.116-0.997, p=0.044) were showed as protective factors against the presence of heart failure with reduced left ventricular ejection fraction, and age (OR 1.643, 95%CI 1.001-3.143, p=0.026), presence of coronary artery disease (OR 6.743, 95%CI 1.932-15.301, p<0.001) and type-2-diabetes mellitus (OR 4.031, 95%CI 1.099-7.231, p<0.001) were associated as risk factors. The adequate expression of thermogenic genes has been shown as possible protective factors against heart failure with reduced ejection fraction, suggesting that a loss of functional epicardial adipose tissue brown-like features would participate in a deleterious manner on heart metabolism. Thermogenic genes could represent a future novel therapeutic target in heart failure.

Right atrium vegetation in prosthetic aortic endocarditis

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Influence of a multidisciplinary alert strategy on mortality due to left-sided infective endocarditis.

INTRODUCTION AND OBJECTIVES Mortality from left-sided infective endocarditis remains very high. The aim of this study was to assess the impact of a multidisciplinary alert strategy (AMULTEI), based on clinical, echocardiographic and microbiological findings, implemented in 2008 in a tertiary hospital. METHODS Cohort study comparing our historical data series (1996-2007) with the number of patients diagnosed with left-sided endocarditis from 2008-2011 (AMULTEI). RESULTS The AMULTEI cohort included 72 patients who were compared with 155 patients in the historical cohort. AMULTEI patients were significantly older (62.5 vs 57.9 years in the historical cohort; P=.047) and had higher comorbidity (Charlson index, 3.33 vs 2.58 in the historical cohort; P=.023). There was also a trend toward more enterococcal etiology in the AMULTEI group (20.8% vs 11.6% in the historical cohort; P=.067). In the AMULTEI group, early surgery was more frequently performed (48.6% vs 23.2%; P<.001) during hospitalization, the incidence of septic shock was significantly lower (9.7% vs 24.5%; P=.009) and there was a trend toward reductions in neurological complications (19.4% vs 29.0%; P=.25) and severe heart failure (12.5% vs 18.7%; P=.24). In-hospital mortality and mortality during the first month of follow-up were significantly lower in the AMULTEI group (16.7% vs 36.1%; P=.003). CONCLUSIONS Despite the trend toward older age and more comorbidity measured by the Charlson index, early mortality was significantly lower in patients treated with the AMULTEI strategy.

Expression of Sterol Regulatory Element-Binding Proteins in epicardial adipose tissue in patients with coronary artery disease and diabetes mellitus: preliminary study

Objectives: Sterol regulatory element-binding proteins (SREBP) genes are crucial in lipid biosynthesis and cardiovascular homeostasis. Their expression in epicardial adipose tissue (EAT) and their influence in the development of coronary artery disease (CAD) and type-2 diabetes mellitus remain to be determined. The aim of our study was to evaluate the expression of SREBP genes in EAT in patients with CAD according to diabetes status and its association with clinical and biochemical data. Methods: SREBP-1 and SREBP-2 mRNA expression levels were measured in EAT from 49 patients with CAD (26 with diabetes) and 23 controls without CAD or diabetes. Results: Both SREBPs mRNA expression were significantly higher in patients with CAD and diabetes (p<0.001) and were identified as independent cardiovascular risk factor for coronary artery disease in patients with type-2 diabetes (SREBP-1: OR 1.7, 95%CI 1.1-2.5, p=0.02; SREBP-2: OR 1.6, 95%CI 1.2-3, p=0.02) and were independently associated with the presence of multivessel CAD, left main and anterior descending artery stenosis, and higher total and LDL cholesterol levels, and lower HDL cholesterol levels, in patients with CAD and diabetes. Conclusions: SREBP genes are expressed in EAT and were higher in CAD patients with diabetes than those patients without CAD or diabetes. SREBP expression was associated as cardiovascular risk factor for the severity of CAD and the poor lipid control. In this preliminary study we suggest the importance of EAT in the lipid metabolism and cardiovascular homeostasis for coronary atherosclerosis of patients with diabetes and highlight a future novel therapeutic target.

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.

Large-scale assessment of aortic stenosis: facing the next cardiac epidemic?

Aims Aortic stenosis (AS) is the most frequent valvular disease in developed countries. As society grows older, the prevalence of AS increases. However, the real burden, current aetiology, severity distribution, and echocardiographic patterns of AS are not fully clear. The aim of the present study is to provide an accurate overall picture of AS, focusing on its epidemiology, aetiology, and echocardiographic features. Methods and results A total of 29 502 consecutive echocardiograpies were prospectively included in this multicentre study. The present sample was composed of patients with advanced age (mean 75.2 years) and similar gender distribution. High proportion (7.2%) showed any grade of AS, with important number of patients (2.8%) presenting severe AS, most of them aged 75 years or more. Coexisting valvular disease appeared in almost half of the sample (49.6%), being the most frequently diagnosed aortic regurgitation (AR) (22%) followed by mitral regurgitation (MR) (15.6%). Degenerative aetiology was found in the vast majority (93.4%) of the studies whereas rheumatic is currently infrequent (3.35%). Low flow-low gradient (LFLG) appeared in 24.6% of patients with severe AS. Atrial fibrillation (23.1% vs. 11.6%; P = 0.002), MR (23.3% vs. 15.1%; P = 0.018), and right ventricle dysfunction (13.3% vs. 5.2%; P = 0.003) appeared frequently in LFLG group. Conclusions Burden of AS is higher than previously assumed. Degenerative aetiology is the main cause of AS. Most of the patients are elder with high prevalence of significant co-existing valvular disease. LFLG severe AS is present in an important proportion of patients, showing high grade of left ventricle remodelling.