Rocio Toro

Clinical usefulness of tissue Doppler imaging in predicting preclinical Fabry cardiomyopathy

UNLABELLED Fabry cardiomyopathy (FC) is characterized by left ventricular hypertrophy (LVH). The aim of this study is to determine whether early changes revealed by tissue Doppler imaging (TDI) are useful for detecting preclinical cardiac abnormalities in patients with this X-linked genetic disorder. If so, this tool could help in deciding whether to begin enzymatic therapy earlier than otherwise. METHODS AND RESULTS 59 consecutive patients with confirmed Fabry disease (FD) underwent conventional and TD echocardiography. FD patients with and without LVH had significantly lower early diastolic tissue Doppler velocities (Ea) compared with the control group (P<0.001); The isovolumic relaxation time (IVRT) was significantly longer in the FD group with LVH (P<0.001). Isovolumic contraction time (IVCT) was significantly shorter in the FD group without LVH compared with the control group (P<0.001). Additionally, peak systolic wall motion velocity (Sa) was significantly lower in patients with LVH, compared with those without LVH (P<0.001). The systolic myocardial velocity correlates inversely with septum and posterior wall thickness (r: -0.74 and r: -0.90; P<0.001 respectively). In respect of predicting preclinical cardiac impairment, the area under the ROC curve of 0.83 suggests an optimal IVRT cut-off point of 60 ms for separating early cardiac impairment from the established condition. This gives a 96.6% specificity rate for the early detection of cardiac involvement. The best parameter for detecting preclinical FC is the IVCT, with a cut-off point of 105 ms, which shows high sensitivity and specificity (100% and 91%, respectively; AUC: 0.97). CONCLUSIONS Myocardial contraction and relaxation evaluation confirms that TDI is a reliable method for early identification of preclinical FC, even before FC patients develop LVH.

Circulating long-non coding RNAs as biomarkers of left ventricular diastolic function and remodelling in patients with well-controlled type 2 diabetes

Contractile dysfunction is underdiagnosed in early stages of diabetic cardiomyopathy. We evaluated the potential of circulating long non-coding RNAs (lncRNAs) as biomarkers of subclinical cardiac abnormalities in type 2 diabetes. Forty-eight men with well-controlled type 2 diabetes and 12 healthy age-matched volunteers were enrolled in the study. Left ventricular (LV) parameters were measured by magnetic resonance imaging. A panel of lncRNAs was quantified in serum by RT-qPCR. No differences in expression levels of lncRNAs were observed between type 2 diabetes patients and healthy volunteers. In patients with type 2 diabetes, long intergenic non-coding RNA predicting cardiac remodeling (LIPCAR) was inversely associated with diastolic function, measured as E/A peak flow (P < 0.050 for all linear models). LIPCAR was positively associated with grade I diastolic dysfunction (P < 0.050 for all logistic models). Myocardial infarction-associated transcript (MIAT) and smooth muscle and endothelial cell-enriched migration/differentiation-associated long noncoding RNA (SENCR) were directly associated with LV mass to LV end-diastolic volume ratio, a marker of cardiac remodelling (P < 0.050 for all linear models). These findings were validated in a sample of 30 patients with well-controlled type 2 diabetes. LncRNAs are independent predictors of diastolic function and remodelling in patients with type 2 diabetes.

Genetic Basis of Dilated Cardiomyopathy

Dilated cardiomyopathy is a rare cardiac disease characterized by left ventricular dilatation and systolic dysfunction leading to heart failure and sudden cardiac death. Currently, despite several conditions have been reported as aetiologies of the disease, a large number of cases remain classified as idiopathic. Recent studies determine that nearly 60% of cases are inherited, therefore due to a genetic cause. Progressive technological advances in genetic analysis have identified over 60 genes associated with this entity, being TTN the main gene, so far. All these genes encode a wide variety of myocyte proteins, mainly sarcomeric and desmosomal, but physiopathologic pathways are not yet completely unraveled. We review the recent published data about genetics of familial dilated cardiomyopathy.

Statins for primary cardiovascular prevention in the elderly

The elderly population is increasing worldwide, with subjects > 65 years of age constituting the fastest-growing age group. Furthermore, the elderly face the greatest risk and burden of cardiovascular disease mortality and morbidity. Although elderly patients, particularly those older > 75, have not been well represented in randomized clinical trials evaluating lipid-lowering therapy, the available evidence supporting the use of statin therapy in primary prevention in older individuals is derived mainly from subgroup analyses and post-hoc data. On the other hand, elderly patients often have multiple co-morbidities that require a high number of concurrent medications; this may increase the risk for drug-drug interactions, thereby reducing the potential benefits of statin therapy. The aim of this review was to present the relevant literature regarding statin use in the elderly for their primary cardiovascular disease, with the associated risks and benefits of treatment.

Familial Dilated Cardiomyopathy Caused by a Novel Frameshift in the BAG3 Gene.

Background Dilated cardiomyopathy, a major cause of chronic heart failure and cardiac transplantation, is characterized by left ventricular or biventricular heart dilatation. In nearly 50% of cases the pathology is inherited, and more than 60 genes have been reported as disease-causing. However, in 30% of familial cases the mutation remains unidentified even after comprehensive genetic analysis. This study clinically and genetically assessed a large Spanish family affected by dilated cardiomyopathy to search for novel variations. Methods and Results Our study included a total of 100 family members. Clinical assessment was performed in alive, and genetic analysis was also performed in alive and 1 deceased relative. Genetic screening included resequencing of 55 genes associated with sudden cardiac death, and Sanger sequencing of main disease-associated genes. Genetic analysis identified a frame-shift variation in BAG3 (p.H243Tfr*64) in 32 patients. Genotype-phenotype correlation identified substantial heterogeneity in disease expression. Of 32 genetic carriers (one deceased), 21 relatives were clinically affected, and 10 were asymptomatic. Seventeen of the symptomatic genetic carriers exhibited proto-diastolic septal knock by echocardiographic assessment. Conclusions We report p.H243Tfr*64_BAG3 as a novel pathogenic variation responsible for familial dilated cardiomyopathy. This variation correlates with a more severe phenotype of the disease, mainly in younger individuals. Genetic analysis in families, even asymptomatic individuals, enables early identification of individuals at risk and allows implementation of preventive measures.

A Novel Mutation in Lamin A/C Causing Familial Dilated Cardiomyopathy Associated With Sudden Cardiac Death

BACKGROUND Dilated cardiomyopathy (DCM), a cardiac heterogeneous pathology characterized by left ventricular or biventricular dilatation, is a leading cause of heart failure and heart transplantation. The genetic origin of DCM remains unknown in most cases, but >50 genes have been associated with DCM. We sought to identify the genetic implication and perform a genetic analysis in a Spanish family affected by DCM and sudden cardiac death. METHODS AND RESULTS Clinical assessment and genetic screening were performed in the index case as well as family members. Of all relatives clinically assessed, nine patients showed clinical symptoms related to the pathology. Genetic screening identified 20 family members who carried a novel mutation in LMNA (c.871 G>A, p.E291K). Family segregation analysis indicated that all clinically affected patients carried this novel mutation. Clinical assessment of genetic carriers showed that electrical dysfunction was present previous to mechanical and structural abnormalities. CONCLUSIONS Our results report a novel pathogenic mutation associated with DCM, supporting the benefits of comprehensive genetic studies of families affected by this pathology.

Efficacy and safety of rivaroxaban in real-life patients with atrial fibrillation.

Rivaroxaban is a once-daily oral anticoagulant currently marketed for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. This indication is largely based on the results of the ROCKET-AF trial. Although these results are robust, studies performed in clinical practice are necessary to confirm these data in real-life patients. These studies have shown rates of stroke and bleeding similar to that found in ROCKET-AF. As an anticoagulant, attention should be paid to making a correct prescription of rivaroxaban, particularly in fragile patients, to reduce the risk of bleeding. In addition, a number of studies have shown that rivaroxaban is cost-effective in clinical practice. Moreover, rivaroxaban is a good alternative to warfarin in patients undergoing elective cardioversion or atrial fibrillation ablation.

Relationship between endothelin-1 levels and pulmonary arterial hypertension in HIV-infected patients.

Objective:Pulmonary arterial hypertension (PAH) is a progressive, fatal disease with average survival of less than 3 years if left untreated. It is most common in patients infected with HIV. Although the pathogenesis in this population is not fully understood, it is thought that HIV infection, through the immune response and release of different inflammatory mediators such as endothelin-1, may contribute directly to endothelial damage. Our objective was to quantify endothelin-1 levels in HIV-infected patients and determine whether or not there is an association between this marker and PAH. Design:A case-control study in patients attending an infectious diseases clinic. Methods:The sample was composed of 79 patients divided into three groups: 23 HIV patients with PAH (HIV+/PAH+), 45 HIV patients without PAH (HIV+/PAH−) and a control group of 11 healthy individuals. The ratio between the HIV+/PAH− and HIV+/PAH+ groups was 2 : 1. Patients were matched by age, sex, risk group and viral load; the control group by age and sex. All patients had blood taken for endothelin-1 plasma quantification. Results:We found lower endothelin-1 levels in the controls than in the HIV+/PAH− group [0.71 pg/ml (interquartile range, IQR 0.54–0.94) vs. 1.13 pg/ml (IQR 0.87–1.38); P = 0.005] and the HIV+/PAH+ cohort [1.16 pg/ml (IQR 0.86–2.37); P = 0.003]. Patients with severe PAH had higher endothelin-1 levels [2.94 pg/ml (IQR 1.81–6.33)] than patients with mild and moderate PAH. Conclusion:Plasma endothelin-1 levels are higher in HIV patients with PAH than in the HIV-noninfected population and levels increase with the severity of the PAH.

Circulating Long Noncoding RNAs in Personalized Medicine: Response to Pioglitazone Therapy in Type 2 Diabetes

Pioglitazone is a thiazolidinedione insulin sensitizer that improves left ventricle (LV) diastolic function in patients with type 2 diabetes mellitus (T2DM) [(1)][1]. Unfortunately, the clinical use of pioglitazone is limited by the risk of adverse effects [(2)][2]. Predictive tools are essential to

Relationship between lipoprotein (a) and micro/macro complications in type 2 diabetes mellitus: a forgotten target

Objectives Increased lipoprotein (a) serum concentrations seems to be a cardiovascular risk factor; this has not been confirmed in extracoronary atherosclerosis complications. We therefore wished to gain a deeper insight into relationship between the plasma concentrations of lipoprotein (a) and the micro- and macro-vascular complications of type 2 diabetes mellitus and to identify possible differences in this association. Methods This is a descriptive observational cross-sectional study. Two-hundred and seventeen elderly patients with type 2 diabetes mellitus were included from the internal medicine outclinic. Anthropometric data, analytical data (insulin reserve, basal and postprandial peptide C, glycosylated hemoglobin, renal parameters, lipid profile and clinical data as hypertension, obesity, micro- and macrovascular complications were collected. Results Patients were grouped according to the type 2 diabetes mellitus time of evolution. The mean plasma concentration of lipoprotein (a) was 22.2 ± 17.3 mg/dL (22.1 ± 15.9 mg/dL for males, and 22.1 ± 18.4 mg/dL for females). Patients with hypertension, coronary heart disease, cerebrovascular accident, microalbuminuria and proteinuria presented a statistically significant increased level of lipoprotein (a). Similarly, the patients with hyperlipoprotein (a) (≥ 30 mg/dL) presented significantly increased levels of urea and total cholesterol. In the multivariate regression model, the level of lipoprotein (a) is positively correlated with coronary heart disease and diabetic nephropathy (P < 0.01 and P < 0.005, respectively). Conclusions The elevation of plasma levels of lipoprotein (a) are associated with the development of coronary heart disease and diabe tic nephropathy. Therefore, we consider that the determination of lipoprotein (a) may be a prognostic marker of vascular complications in patients with type 2 diabetes mellitus.