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Hypertrophic cardiomyopathy; Myectomy; Sudden cardiac death Miocardiopatia hipertròfica; Miectomia; Mort cardíaca sobtada Miocardiopatía hipertrófica; Miectomía; Muerte cardíaca súbita Hypertrophic cardiomyopathy is a heart muscle disease with an annual incidence between 0.24 and 0.47/100000 in childhood. Sudden cardiac death is the most common cause of death in this population. Although some medical treatment can decrease the risk of sudden cardiac death, implantable cardioverter defibrillator continues to be the most reliable treatment. Different types of devices and programming strategies can be used in patients with hypertrophic cardiomyopathy depending on each center and specific patient condition. We report a pediatric patient affected with hypertrophic cardiomyopathy who had and ICD implantation in primary prevention. Four years later he developed symptomatic left ventricular outflow tract obstruction and a surgical septal myectomy was performed. After the myectomy the patient developed complete left bundle branch block on his 12 lead ECG, and unfortunately none of the S-ICD vectors were suitable after the myectomy and it had to be explanted and replaced for a new transvenous ICD.

Cardiovascular risk; Myocardial insulin resistance; Type 2 diabetes Risc cardiovascular; Resistència miocàrdica a la insulina; Diabetis tipus 2 Riesgo cardiovascular; Resistencia miocárdica a la insulina; Diabetes tipo 2 Background: Systemic insulin resistance is generally postulated as an independent risk factor of cardiovascular events in type 2 diabetes (T2D). However, the role of myocardial insulin resistance (mIR) remains to be clarified. Methods: Two 18F-FDG PET/CT scans were performed on forty-three T2D patients at baseline and after hyperinsulinemic–euglycemic clamp (HEC). Myocardial insulin sensitivity (mIS) was determined by measuring the increment in myocardial 18F-FDG uptake after HEC. Coronary artery calcium scoring (CACs) and myocardial radiodensity (mRD) were assessed by CT. Results: After HEC, seventeen patients exhibited a strikingly enhancement of myocardial 18F-FDG uptake and twenty-six a marginal increase, thus revealing mIS and mIR, respectively. Patients with mIR showed higher mRD (HU: 38.95 [33.81–44.06] vs. 30.82 [21.48–38.02]; p = 0.03) and CACs > 400 (AU: 52% vs. 29%; p = 0.002) than patients with mIS. In addition, HOMA-IR and mIS only showed a correlation in those patients with mIR. Conclusions: 18F-FDG PET combined with HEC is a reliable method for identifying patients with mIR. This subgroup of patients was found to be specifically at high risk of developing cardiovascular events and showed myocardial structural changes. Moreover, the gold-standard HOMA-IR index was only associated with mIR in this subgroup of patients. Our results open up a new avenue for stratifying patients with cardiovascular risk in T2D. This research was funded by the Carlos III Health Institute and the European Regional Development Fund (PI16/02064 and PI20/01588) and AGAUR (2017SGR1303 and 2017SGR1144).

Cardiomyopathy; Diagnosis; Prognosis Miocardiopatía; Diagnóstico; Pronóstico Miocardiopatia; Diagnòstic; Pronòstic Cardiomyopathies are a group of structural and/or functional myocardial disorders which encompasses hypertrophic, dilated, arrhythmogenic, restrictive, and other cardiomyopathies. Multimodality cardiac imaging techniques are the cornerstone of cardiomyopathy diagnosis; transthoracic echocardiography should be the first-line imaging modality due to its availability, and diagnosis should be confirmed by cardiovascular magnetic resonance, which will provide more accurate morphologic and functional information, as well as extensive tissue characterization. Multimodality cardiac imaging techniques are also essential in assessing the prognosis of patients with cardiomyopathies; left ventricular ejection fraction and late gadolinium enhancement are two of the main variables used for risk stratification, and they are incorporated into clinical practice guidelines. Finally, periodic testing with cardiac imaging techniques should also be performed due to the evolving and progressive natural history of most cardiomyopathies.

A recent genome-wide association study (GWAS) identified a locus in chromosome 11 associated with the chronic cardiac form of Chagas disease. Here we aimed to elucidate the potential functional mechanism underlying this genetic association by analyzing the correlation among single nucleotide polymorphisms (SNPs) and DNA methylation (DNAm) levels as cis methylation quantitative trait loci (cis-mQTL) within this region. A total of 2,611 SNPs were tested against 2,647 DNAm sites, in a subset of 37 chronic Chagas cardiomyopathy patients and 20 asymptomatic individuals from the GWAS. We identified 6,958 significant cis-mQTLs (False Discovery Rate [FDR], Author summary Genome-wide association studies (GWAS) have provided extensive information regarding the genetic component of complex traits, including parasitic diseases such as Chagas disease. However, these associations mapped in regulatory regions of the genome and assigning them a functional consequence have been cumbersome. In this study we aimed to evaluate the functional mechanism underlying the previously reported genomic association with chronic Chagas cardiomyopathy, by assessing the correlation between methylation changes and the underlying genetic variations within the region. These methylation quantitative trait loci (mQTLs) may be involved in gene expression regulation. We identified mQTLs in three genes that have been associated with cardiovascular diseases in previous studies. Interestingly, one of these genes was previously identified as differentially methylated and expressed in heart biopsies of chronic Chagas cardiomyopathy patients. Our results suggest novel genes that could play a role in the chronic Chagas cardiomyopathy, evidencing the functional relevance of the previously associated loci.

Cardiovascular risk; Myocardial insulin resistance; Non-alcoholic fatty liver disease Riesgo cardiovascular; Resistencia a la insulina del miocardio; Enfermedad del higado graso no alcoholico Risc cardiovascular; Resistència a la insulina del miocardi; Malaltia del fetge gras no alcohòlic Background: We report that myocardial insulin resistance (mIR) occurs in around 60% of patients with type 2 diabetes (T2D) and was associated with higher cardiovascular risk in comparison with patients with insulin-sensitive myocardium (mIS). These two phenotypes (mIR vs. mIS) can only be assessed using time-consuming and expensive methods. The aim of the present study is to search a simple and reliable surrogate to identify both phenotypes. Methods: Forty-seven patients with T2D underwent myocardial [18F]FDG PET/CT at baseline and after a hyperinsulinemic–euglycemic clamp (HEC) to determine mIR were prospectively recruited. Biochemical assessments were performed before and after the HEC. Baseline hepatic steatosis index and index of hepatic fibrosis (FIB-4) were calculated. Furthermore, liver stiffness measurement was performed using transient elastography. Results: The best model to predict the presence of mIR was the combination of transaminases, protein levels, FIB-4 score and HOMA (AUC = 0.95; sensibility: 0.81; specificity: 0.95). We observed significantly higher levels of fibrosis in patients with mIR than in those with mIS (p = 0.034). In addition, we found that patients with mIR presented a reduced glucose uptake by the liver in comparison with patients with mIS. Conclusions: The combination of HOMA, protein, transaminases and FIB-4 is a simple and reliable tool for identifying mIR in patients with T2D. This information will be useful to improve the stratification of cardiovascular risk in T2D. This work was supported by the Carlos III Health Institute and the European Regional Development Fund (PI16/02064, PI20/01588) and the Agency for Management of University and Research Grants (AGAUR) of Catalonia (2017SGR1303).

Connexin 43 (Cx43) is essential for cardiac electrical coupling, but its effects on myocardial fibrosis is controversial. Here, we analyzed the role of Cx43 in myocardial fibrosis caused by angiotensin II (AngII) using Cx43fl/fl and Cx43Cre-ER(T)/fl inducible knock-out (Cx43 content: 50%) mice treated with vehicle or 4-hydroxytamoxifen (4-OHT) to induce a Cre-ER(T)-mediated global deletion of the Cx43 floxed allele. Myocardial collagen content was enhanced by AngII in all groups (n = 8&ndash, 10/group, p &lt, 0.05). However, animals with partial Cx43 deficiency (vehicle-treated Cx43Cre-ER(T)/fl) had a significantly higher AngII-induced collagen accumulation that reverted when treated with 4-OHT, which abolished Cx43 expression. The exaggerated fibrotic response to AngII in partially deficient Cx43Cre-ER(T)/fl mice was associated with enhanced p38 MAPK activation and was not evident in Cx43 heterozygous (Cx43+/-) mice. In contrast, normalization of interstitial collagen in 4-OHT-treated Cx43Cre-ER(T)/fl animals correlated with enhanced MMP-9 activity, IL-6 and NOX2 mRNA expression, and macrophage content, and with reduced &alpha, SMA and SM22&alpha, in isolated fibroblasts. In conclusion, our data demonstrates an exaggerated, p38 MAPK-dependent, fibrotic response to AngII in partially deficient Cx43Cre-ER(T)/fl mice, and a paradoxical normalization of collagen deposition in animals with an almost complete Cx43 ablation, an effect associated with increased MMP-9 activity and inflammatory response and reduced fibroblasts differentiation.