Background—: Recent exome sequencing studies identified filamin C ( FLNC ) as a candidate gene for hypertrophic cardiomyopathy (HCM). Our aim was to determine the rate of FLNC candidate variants in a large cohort of HCM patients who were also sequenced for the main sarcomere genes. Methods and Results—: A total of 448 HCM patients were next generation–sequenced (semiconductor chip technology) for the MYH7, MYBPC3 , TNNT2 , TNNI3 , ACTC1 , TNNC1 , MYL2 , MYL3 , TPM1 , and FLNC genes. We also sequenced 450 healthy controls from the same population. Based on the reported population frequencies, bioinformatic criteria, and familial segregation, we identified 20 FLNC candidate variants (13 new; 1 nonsense; and 19 missense) in 22 patients. Compared with the patients, only 1 of the control’s missense variants was nonreported ( P =0.007; Fisher exact probability test). Based on the familial segregation and the reported functional studies, 6 of the candidate variants (in 7 patients) were finally classified as likely pathogenic, 10 as variants of uncertain significance, and 4 as likely benign. Conclusions—: We provide a compelling evidence of the involvement of FLNC in the development of HCM. Most of the FLNC variants were associated with mild forms of HCM and a reduced penetrance, with few affected in the families to confirm the segregation. Our work, together with others who found FLNC variants among patients with dilated and restrictive cardiomyopathies, pointed to this gene as an important cause of structural cardiomyopathies.

Transcatheter aortic valve implantation (TAVI) is a rapidly evolving therapeutic modality currently available for patients with severe aortic stenosis (AS) that are unsuitable for surgery because of technical/anatomical issues or high-estimated surgical risk. Transfemoral approach is the preferred TAVI delivery route when possible. Alternative non-transfemoral access options include transaortic, trans-subclavian and transapical access. Other approaches are also feasible (transcarotid, transcaval, and antegrade aortic) but are restricted to operators and hospitals with experience. The peculiarities of each of the vascular approaches designed for TAVI delivery make it necessary to carefully assess patient’s atherosclerotic load and location, arterial size and tortuosity, and presence of mural thrombus. Several clinical trials are currently ongoing and in the near future the indications for these approaches will likely be better defined and extended to a broader spectrum of TAVI candidates.

Background and Aims: The effectiveness of systemic treatment in advanced hepatocellular carcinoma (HCC) depends on the selection of patients, management of cirrhosis complications and expertise to treat adverse events. The aims of the study are to assess the frequency and management of cardiovascular events in HCC patients treated with sorafenib (SOR) and to create a scale to predict the onset of major adverse cardiovascular events (MACE).Method: Observational retrospective study with consecutive HCC patients treated with SOR between 2007 and 2019 in a western centre. In order to classify cardiovascular risk pre‐SOR, we designed the CARDIOSOR scale with age, hypertension, diabetes, dyslipidaemia and peripheral vascular disease. Other adverse events, dosing and outcome data were collected during a homogeneous protocolled follow‐up.Results: Two hundred ninety‐nine patients were included (219 BCLC‐C). The median overall survival was 11.1 months (IQR 5.6‐20.5), and duration of treatment was 7.4 months (IQR 3.3‐14.7). Seventeen patients (6%) stopped SOR due to cardiovascular event. Thirty‐three patients suffered MACE (7 heart failure, 11 acute coronary syndrome, 12 cerebrovascular accident and 8 peripheral vascular ischemia); 99 had a minor cardiovascular event, mainly hypertension (n = 81). Age was the only independent factor associated to MACE (HR 1.07; 95% CI 1.03‐1.12; P = .002). The CARDIOSOR scale allows to identify the group of patients with higher risk of MACE (sHR 3.4; 95% CI 1.4‐6.7; P = .04).Conclusion: The incidence of cardiovascular events in HCC patients treated with SOR is higher than expected. Multidisciplinary approach and clinical tools like CARDIOSOR scale could be helpful to manage these patients.

Introduction: Mortality caused by ST elevation myocardial infarction (STEMI) has declined because of greater use of primary percutaneous coronary intervention (PCI). It is unknown if patients >75 have similar survival as peers. We aim to know it stratifying by sex and assessing how the sex may impact the survival. Methods: We retrospectively selected all patients >75 who suffered a STEMI treated with primary PCI at our institution. We compared their survival with that of the reference population (general population matched by age, sex, and geographical region). A Cox-regression analysis controlling for clinical factors was performed to know if sex was a risk factor. Results: Total of 450 patients were studied. Survival at 1, 3, and 5 years of follow-up for patients who survived the first 30 days was 91.22% (CI95% 87.80–93.72), 79.71% (CI95% 74.58–83.92), and 68.02% (CI95% 60.66–74.3), whereas in the reference population it was 93.11%, 79.10%, and 65.01%, respectively. Sex was not a risk factor, Hazard Ratio = 1.02 (CI95% 0.67-1.53; p = 0.92). Conclusions: Life expectancy of patients suffering a STEMI is nowadays intimately linked to survival in the first 30 days. After one year, the risk of death for both men and women seems similar to that of the general population.

Aim: The long noncoding RNA H19 and its host micro RNA miR-675 have been found deregulated in cardiac hypertrophy and heart failure tissues. Our aim was to investigate whether the H19 gene variants were associated with the risk of hypertrophic cardiomyopathy (HCM). Patients & methods: We genotyped two H19 tag single nucleotide polymorphisms in 405 HCM patients and 550 controls, and sequenced this gene in 100 patients. Results: The rs2107425 C was significantly increased in sarcomere no-mutation patients (n = 225; p = 0.01): CC versus CT + TT, p = 0.017; odd ratios: 1.51. Sequencing of the H19 coding transcript identified two patients heterozygous carriers for a rare variant, rs945977096 G/A, that was absent among the controls. Conclusion: Our study suggested a significant association between H19 variants and the risk of developing HCM.