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Instituto de Salud Carlos III (ISCIII), European Regional Development Fund/European Social Fund "A way to make Europe"/" Investing in your future" [PI18/0004, PI20/0320, PT17/0015/0043]; ISCIII; MCIN; Pro-CNIC Foundation; Severo Ochoa Centers of Excellence program [CEX2020-001041-S]; ISCIII [CM20/00101], Frutos F. de, Ochoa JP, Navarro-Peñalver M, Baas A, Bjerre JV, Zorio E, Méndez I, Lorca R, Verdonschot JAJ, García-Granja PE, Bilinska Z, Fatkin D, Fuentes-Cañamero ME, García-Pinilla JM, García-Álvarez MI, Girolami F, Barriales-Villa R, Díez-López C, Lopes LR, Wahbi K, García-Álvarez A, Rodríguez-Sánchez I, Rekondo-Olaetxea J, Rodríguez-Palomares JF, Gallego-Delgado M, Meder B, Kubanek M, Hansen FG, Restrepo-Córdoba MA, Palomino-Doza J, Ruiz-Guerrero L, Sarquella-Brugada G, Perez-Perez AJ, Bermúdez-Jiménez FJ, Ripoll-Vera T, Rasmussen TB, Jansen M, Sabater-Molina M, Elliot PM, Garcia-Pavia P; European Genetic Cardiomyopathies Initiative Investigators

INTRODUCTION AND OBJECTIVES According to the wavefront phenomenon described in the late 1970s, myocardial infarction triggered by acute coronary occlusion progresses with increasing duration of ischemia as a transmural wavefront from the subendocardium toward the subepicardium. However, whether wavefront progression of necrosis also occurs laterally has been disputed. We aimed to assess the transmural and lateral spread of myocardial damage after acute myocardial infarction in humans and to evaluate the impact of metoprolol on these. METHODS We assessed myocardial infarction in the transmural and lateral dimensions in a cohort of 220 acute ST-segment elevation myocardial infarction (STEMI) patients from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction). The patients underwent cardiac magnetic resonance imaging at 5 to 7 days and 6 months post-STEMI. RESULTS On day 5 to 7 post-STEMI cardiac magnetic resonance, there was a strong linear correlation between the transmural and lateral extent of infarction (delayed gadolinium enhancement) (r=-0.88; P

Resumen Introduccion y objetivos Esta establecido que la necrosis secundaria a una oclusion coronaria se inicia en el subendocario y progresa hacia el subepicardio. Sin embargo, hay controversia sobre la posibilidad de que la onda de progresion del infarto sea lateral, ademas de transmural, y es el objetivo de este trabajo. Metodos Se estudio la extension del infarto en las dimensiones transmural y lateral en 220 pacientes con infarto agudo de miocardio del ensayo METOCARD-CNIC (Efecto del metoprolol en la cardioproteccion durante un infarto agudo de miocardio). Los pacientes se sometieron a 2 resonancias magneticas. Resultados En la resonancia de los dias 5-7 posinfarto, se encontro una fuerte correlacion lineal entre las extensiones transmural y lateral del infarto (realce tardio de gadolinio) (r = -0,88; p Conclusiones Nuestros hallazgos cuestionan el dogma de que la progresion del infarto solo se produce en sentido transmural. Mostramos que el infarto progresa de forma circunferencial (en sentido tanto transmural como lateral). Esto implica que las terapias cardioprotectoras pueden asociarse con miocardio salvado en los bordes laterales del infarto. Este estudio ha sido registrado en ClinicalTrial.gov (Identificador: NCT01311700).

Resumen Introduccion y objetivos El tratamiento medico y las medidas de prevencion secundaria en el infarto agudo de miocardio con elevacion del segmento ST (IAMCEST) han experimentado una mejora progresiva en las ultimas decadas. A pesar de ello, los pacientes > 65 anos presentan un mayor riesgo de muerte tras un evento coronario. Nuestro objetivo fue evaluar si los pacientes Metodos Todos los pacientes que sufrieron un IAMCEST en los ultimos 6 anos en nuestro centro fueron incluidos en un estudio observacional (SurviSTEMI: survival in STEMI). Se calculo la supervivencia observada, la supervivencia esperada y el exceso de mortalidad. Se repitieron todos los analisis estratificando por grupo etario Resultados Para los pacientes Conclusiones Los supervivientes del IAMCEST presentan una esperanza de vida similar a la de la poblacion general de la misma edad, sexo y area geografica.

The RASopathies are a family of clinically related disorders caused by mutations affecting genes participating in the RAS-MAPK signaling cascade. Among them, Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) are allelic conditions principally associated with dominant mutations in PTPN11, which encodes the nonreceptor SH2 domain-containing protein tyrosine phosphatase SHP2. Individual PTPN11 mutations are specific to each syndrome and have opposite consequences on catalysis, but all favor SHP2's interaction with signaling partners. Here, we report on a subject with NS harboring biallelic variants in PTPN11. While the former (p.Leu261Phe) had previously been reported in NS, the latter (p.Thr357Met) is a novel change impairing catalysis. Members of the family carrying p.Thr357Met, however, did not show any obvious feature fitting NSML or within the RASopathy phenotypic spectrum. A major impact of this change on transcript processing and protein stability was excluded. These findings further support the view that NSML cannot be ascribed merely to impaired SHP2's catalytic activity and suggest that PTPN11 mutations causing this condition act through an alternative dominant mechanism.

Mitochondrial DNA (mtDNA) differs from the nuclear genome in many aspects: a maternal inheritance pattern; being more prone to acquire somatic de novo mutations, accumulative with age; and the possible coexistence of different mtDNA alleles (heteroplasmy). Mitochondria are key cellular organelles responsible for energy production and involved in complex mechanisms, including atherosclerosis. In this scenario, we aimed to evaluate mtDNA variants that could be associated with premature cardiovascular disease. We evaluated 188 consecutive patients presenting with premature myocardial infarction with ST elevation (STEMI) confirmed by coronary angiogram. mtDNA polymorphisms and clinical data were evaluated and compared with 271 individuals from the same population (control group). Tobacco consumption (80.85% vs. 21.21%, p < 0.01) and dyslipidemia (38.83% vs. 28.41%, p = 0.02) were significantly more frequent among STEMI patients. Moreover, C16223T mtDNA mutation and poly-C heteroplasmy were significantly more frequent among premature STEMI male patients than in controls. The OR associated C16223T mtDNA with the increased presence of cardiovascular risk factors. Our data suggest that mtDNA 16223T and heteroplasmy may be associated with unstable premature atherosclerosis disease in men. Moreover, the presence of cardiovascular risk factors (CVRFs) was associated with C16223T mtDNA, with a cumulative effect. Protective mitochondrial pathways are potential therapeutic targets. Preventing exposure to the damaging mechanisms associated with CVRFs is of utmost importance.

Heart transplantation remains the gold standard for the treatment of advanced heart failure (HF). Identification of the etiology of HF is mandatory, as the specific pathology can determine subsequent treatment. Early identification of familial hypercholesterolemia (FH), the most common genetic disorder associated with premature cardiovascular disease, has a potential important impact on clinical management and public health. We evaluated the genetic information in the genes associated with FH in a cohort of 140 heart-transplanted patients. All patients underwent NGS genetic testing including LDLR, APOB, and PCSK9. We identified four carriers of rare pathogenic variants in LDLR and APOB. Although all four identified carriers had dyslipidemia, only the one carrying the pathogenic variant LDLR c.676T>C was transplanted due to CAD. Another patient with heart valvular disease was carrier of the controversial LDLR c.2096C>T. Two additional patients with non-ischemic dilated cardiomyopathy were carriers of variants in APOB (c.4672A>G and c.5600G>A). In our cohort, we identified the genetic cause of FH in patients that otherwise would not have been diagnosed. Opportunistic genetic testing for FH provides important information to perform personalized medicine and risk stratification not only for patients but also for relatives at concealed high cardiovascular risk. Including the LDLR gene in standard NGS cardiovascular diagnostics panels should be considered.

Familial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular (CV) disease (ASCVD). However, it still is severely underdiagnosed. Initiating lipid-lowering therapy (LLT) in FH patients early in life can substantially reduce their ASCVD risk. As a result, identifying FH is of the utmost importance. The increasing availability of genetic testing may be useful in this regard. We aimed to evaluate the genetic profiles, clinical characteristics, and gender differences between the first consecutive patients referred for genetic testing with FH clinical suspicion in our institution (a Spanish cohort). Clinical information was reviewed, and all participants were sequenced for the main known genes related to FH: LDLR, APOB, PCSK9 (heterozygous FH), LDLRAP1 (autosomal recessive FH), and two other genes related to hyperlipidaemia (APOE and LIPA). The genetic yield was 32%. Their highest recorded LDLc levels were 294 ± 65 SD mg. However, most patients (79%) were under > 1 LLT medication, and their last mean LDLc levels were 135 ± 51 SD. LDLR c.2389+4A>G was one of the most frequent pathogenic/likely pathogenic variants and its carriers had significantly worse LDLc highest recorded levels (348 ± 61 SD vs. 282 ± 60 SD mg/dL, p = 0.002). Moreover, we identified an homozygous carrier of the pathogenic variant LDLRAP1 c.207delC (autosomal recessive FH). Both clinical and genetic hypercholesterolemia diagnosis was significantly established earlier in men than in women (25 years old ± 15 SD vs. 35 years old ± 19 SD, p = 0.02; and 43 ± 17 SD vs. 54 ± 19 SD, p = 0.02, respectively). Other important CV risk factors were found in 44% of the cohort. The prevalence of family history of premature ASCVD was high, whereas personal history was exceptional. Our finding reaffirms the importance of early detection of FH to initiate primary prevention strategies from a young age. Genetic testing can be very useful. As it enables familial cascade genetic testing, early prevention strategies can be extended to all available relatives at concealed high CV risk.

ObjectiveOne of the challenges in hypertrophic cardiomyopathy (HCM) is to determine the pathogenicity of genetic variants and to establish genotype/phenotype correlations. This study aimed to: (1) demonstrate that MYBPC3 c.2149–1G>A is a founder pathogenic variant, (2) describe the phenotype and clinical characteristics of mutation carriers and (3) compare these patients with those with the most frequent pathogenic HCM variants: MYBPC3 p.Arg502Trp/Gln.MethodsWe reviewed genetic tests performed in HCM probands at our institution. We carried out transcript analyses to demonstrate the splicing effect, and haplotype analyses to support the founder effect of MYBPC3 c.2149–1G>A. Carriers with this mutation were compared with those from MYBPC3 p.Arg502Trp/Gln in terms of presentation features, imaging and outcomes.ResultsMYBPC3 c.2149–1G>A was identified in 8 of 570 probands and 25 relatives. Penetrance was age and sex dependent, 50.0% of the carriers over age 36 years and 75.0% of the carriers over 40 years showing HCM. Penetrance was significantly higher in males: in carriers older than 30 years old, 100.0% of males vs 50.0% of females had a HCM phenotype (p=0.01). Males were also younger at diagnosis (32±13 vs 53±10 years old, pMYBPC3 c.2149–1G>A resulted in an abnormal transcript that led to haploinsufficiency and was segregated in two haplotypes. However, both came from one founder haplotype. Affected carriers showed a better functional class and higher left ventricular ejection fraction (LVEF) than patients with MYBPC3 p.Arg502Trp/Gln (pConclusionsMYBPC3 c.2149–1G>A splicing variant is a founder mutation. Affected males show an early onset of HCM and with higher penetrance than women. Carriers show better functional class and higher LVEF than MYBPC3 p.Arg502Trp/Gln carriers, but a similar rate of major adverse outcomes.

Background The aim of this study was to assess the safety and effectiveness of valve in valve (VIV) TAVI with the autoexpandable valve, specifically in patients with failed Mitroflow (MF) bioprosthetic aortic valves. Methods Pilot, single center, observational and prospective study that included 45 consecutive patients with symptomatic failed MF bioprosthetic aortic valve, referred for VIV TAVI. The safety primary endpoint was a composite of early events at 30 days, defined by VARC-2 criteria. The efficacy primary endpoint was the device success (no procedural mortality, correct positioning of a single prosthetic heart valve into the proper anatomical location and absence of moderate/severe prosthetic aortic valve regurgitation). We also analysed patient-prosthesis mismatch (PPM) parameters. Results Between March 2012 to December 2017, 45 symptomatic patients (age 79.9 ± 6.5 years) with degenerated MF valves (numbers 19: 33.3%; 21: 28.9%; 23: 24.4%; 25: 13.3%) underwent CoreValve (n = 11) or Evolut R (n = 34) implantation (23 and 26 mm sizes). The STS predicted risk of mortality was 6.3 ± 6.3%. The safety primary endpoint occurred in 4 patients (8.8%). The efficacy endpoint was present in all patients (100%). There were no coronary occlusions or procedural deaths. The number of patients with any degree of PPM raised from 51.1% (pre-TAVI) to 60% (post-TAVI). Conclusions Self-expanding TAVI for degenerated MF bioprosthesis has favourable early outcomes. The VIV procedure has provided an important gateway to avoiding high-risk redo surgery and is now a potential option for MF failed surgically aortic implanted valves.

Resumen Introduccion y objetivos La miocardiopatia hipertrofica (MCH) es la enfermedad cardiaca hereditaria mas frecuente. El desafio actual radica en la clasificacion precisa de la patogenicidad de variantes asociadas a las MCH. Para la evaluacion inicial de la MCH se recomienda una ecocardiografia transtoracica (ETT). La cardiorresonancia magnetica (CRM) tambien debe considerarse. El objetivo fue revaluar la penetrancia y expresion clinica de la variante patogenica MYBPC3 p.G263*. Metodos Se estudiaron los principales genes sarcomericos, mediante next-generation sequencing, en 384 indices con MCH y una cohorte control de 450 individuos sanos. Se identificaron todos portadores de MYBPC3 p.G263* y se realizo cribado familiar. Se recogio informacion clinica de manera retrospectiva hasta 2015 y prospectiva a partir de entonces. Se realizo un esfuerzo extra para realizar CRM en todos los portadores de la variante independientemente del resultado de la ETT. Resultados Trece casos indice con MCH y ninguno de la cohorte control eran portadores de la variante MYBPC3 p.G263*, patogenica segun el American College of Medical Genetics and Genomics y la Association for Molecular Pathology. Mediante cribado familiar se identifico a un total de 39 portadores. La mayoria se diagnostico de MCH asintomatica, con inicio tardio de la enfermedad y un curso relativamente benigno, pero con potenciales complicaciones tardias. Se encontro una penetrancia cercana al 70% evaluada por la ETT y del 87% por CRM. La penetrancia era edad-dependiente, y alcanzo el 100% en mayores de 55 anos. Conclusiones MYBPC3 p.G263* comparte con la mayoria de las variantes patogenicas truncantes en este gen un inicio tardio, un curso relativamente benigno en los jovenes y una alta penetrancia. La CRM podria ser una herramienta util en la evaluacion de portadores independientemente de la ETT.

The aim of this study was to determine if modifying the classical implantation technique for self-expanding (SE) transcatheter aortic valve replacement to a novel cusp-overlapping projection (COP) technique results in a higher implantation depth (ID) and subsequently reduces the rate of permanent pacemaker implantation (PPMI).The COP technique presents the potential benefit of an optimized ID to reduce the rate of PPMI. However, only a few studies have compared clinical outcomes with those achieved using the standard technique. This is the first study to systematically evaluate this approach for SE transcatheter heart valves (THVs) in different populations METHODS: Beginning in February 2015, 444 patients were consecutively included. Propensity score matching was used to control baseline characteristics because of the observational nature of the study. In total, 161 pairs of patients were analyzed. Three methods were used to measure ID (noncoronary cusp [NCC] to the THV, mean of the NCC and the left coronary cusp [LCC] to the THV, and the deepest edge from the LCC and the NCC to the THV).ID was significantly higher in COP cases when measuring from the NCC (4.2 mm vs 5.3 mm; P 0.001) and the mean from the NCC and the LCC (5.3 mm vs 5.9 mm; P = 0.04), but not from the deepest edge. The PPMI rate was lower in the COP group: 19 (11.8%) vs 35 (21.7%) (P = 0.03; relative risk: 0.54; 95% CI: 0.32-0.91).The present study showed that the COP technique significantly reduces PPMI in SE THV implantation compared with the classical implantation technique, with similar rates of complications.

Background: Precise evaluation of the degree of frailty is a fundamental part of the global geriatric assessment that helps to avoid therapies that could be futile. Our main objective was to determine the prevalence of frailty in a specific consult of patients undergoing aortic valve replacement. Methods: From May 2018 to February 2020, all consecutive patients ≥75 years old, with severe symptomatic aortic stenosis, undergoing valve replacement in the Principality of Asturias (Northern Spain) were evaluated. Results: A total of 286 patients were assessed. The mean age was 84 ± 4.01 years old, 175 (61.2%) were female. The short performance physical battery score was 8.5 ± 2.4 and the prevalence of frailty was 19.6% (56 patients). In the multivariable analysis, age, Barthel index and atrial fibrillation were independent predictors of frailty. Conclusions: The prevalence of frailty in our sample patients undergoing aortic valve replacement, evaluated by a standardized protocol, was 19.6%.

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.

Highlights • The Angiotensin system has been implicated in the pathogenesis of COVID-19. • Functional ACE/ACE2 polymorphisms might contribute to the outcome of COVID-19. • Severe COVID-19 was associated with hypertension, male gender, and ACE-DD genotype. • The ACE2 polymorphism was not associated with the disease outcome. • ACE2 showed no coding variants that could explain an increased risk of COVID-19., The Angiotensin system is implicated in the pathogenesis of COVID-19. First, ACE2 is the cellular receptor for SARS-CoV-2, and expression of the ACE2 gene could regulate the individuaĺs susceptibility to infection. In addition, the balance between ACE1 and ACE2 activity has been implicated in the pathogenesis of respiratory diseases and could play a role in the severity of COVID-19. Functional ACE1/ACE2 gene polymorphisms have been associated with the risk of cardiovascular and pulmonary diseases, and could thus also contribute to the outcome of COVID-19. We studied 204 COVID-19 patients (137 non-severe and 67 severe-ICU cases) and 536 age-matched controls. The ACE1 insertion/deletion and ACE2 rs2285666 polymorphism were determined. Variables frequencies were compared between the groups by logistic regression. We also sequenced the ACE2 coding nucleotides in a group of patients. Severe COVID-19 was associated with hypertension male gender (p

Familial hypercholesterolemia (FH) is an underdiagnosed genetic inherited condition that may lead to premature coronary artery disease (CAD). FH has an estimated prevalence in the general population of about 1:313. However, its prevalence in patients with premature STEMI (ST-elevation myocardial infarction) has not been widely studied. This study aimed to evaluate the prevalence of FH in patients with premature STEMI. Cardiovascular risk factors, LDLc (low-density lipoprotein cholesterol) evolution, and differences between genders were also evaluated. Consecutive patients were referred for cardiac catheterization to our center due to STEMI suspicion in 2018. From the 80 patients with confirmed premature CAD (men &lt, 55 and women &lt, 60 years old with confirmed CAD), 56 (48 men and eight women) accepted to be NGS sequenced for the main FH genes. Clinical information and DLCN (Dutch Lipid Clinic Network) score were analyzed. Only one male patient had probable FH (6&ndash, 7 points) and no one reached a clinically definite diagnosis. Genetic testing confirmed that the only patient with a DLCN score &ge, 6 has HF (1.8%). Smoking and high BMI the most frequent cardiovascular risk factors (&gt, 80%). Despite high doses of statins being expected to reduce LDLc levels at STEMI to current dyslipidemia guidelines LDL targets (&lt, 55 mg/dL), LDLc control levels were out of range. Although still 5.4 times higher than in general population, the prevalence of FH in premature CAD is still low (1.8%). To improve the genetic yield, genetic screening may be considered among patients with probable or definite FH according to clinical criteria. The classical cardiovascular risk factors prevalence far exceeds FH prevalence in patients with premature STEMI. LDLc control levels after STEMI were out range, despite intensive hypolipemiant treatment. These findings reinforce the need for more aggressive preventive strategies in the young and for intensive lipid-lowering therapy in secondary prevention.

Apoliprotein B (ApoB) has been associated with hypercholesterolemia and ischemic coronary disease. This study was aimed to determine the effect of two APOB gene variants in the risk of developing early-onset coronary artery disease (EO-CAD) in a Spanish population. The association of these polymorphisms with hypercholesterolemia was also analysed.The study involved a total of 889 healthy population controls (397 male) and 790 EO-CAD cases (636 male; EO-CAD was defined as male60 years and women65 years). All the patients had at least one vessel with angiography documented atherosclerotic lesion. Patients and controls were genotyped for the APOB variants rs1801701 A/G (p.R3638Q) and rs1367117 C/T (p.T98I). Allele and genotype frequencies were compared between the groups (patients vs. controls, hyper-vs. normo-cholesterolemia) by logistic regression. The rs1801701 was significantly associated with EO-CAD in male (OR = 1.44, 95%CI = 1.05-1.99) and female (OR = 2.22, 95%CI = 1.58-3.14). This SNP was significantly associated with hypercholesterolemia in female, with a trend in male. The association with EO-CAD was independent of hypercholesterolemia (multiple logistic regression).A common APOB polymorphism (rs1801701) was an independent risk factor for EO-CAD in our population. The risk-effect was more significant in female than in male.

Functional mitral regurgitation (MR) could be defined as a ventricular disease where mitral valve is structurally normal, left chambers are enlarged and mitral annulus is dilated with lack of coaptation of leaflets. Transcatheter mitral valve repair technique has broadened the therapeutic range in the treatment of severe MR. The aim of this study was to review outcomes of MitraClip vs. medical treatment for functional MR. We also planned to review the concept of functional MR, assessment of the degree, prognosis and therapy options. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Medline through PubMed database was used to search. The present review included manuscripts published between January 2009 and September 2019. Two authors independently screened titles and abstracts of all publications, and performed the selection of studies and data extraction. In the case of disagreements, consensus meetings reached the final decision. Inclusion criteria were: (I) randomized controlled trials and (II) works must compare MitraClip versus optimal medical treatment. Transcatheter mitral valve repair along optimal medical treatment has been compared with optimal medical therapy in two different randomized trials. In the COAPT trial, the MitraClip group showed a significant reduction in mortality and heart failure (HF) hospitalizations. In the MITRA-FR trial, no significant differences were observed between both groups. We reviewed important aspects of functional MR and performed a comprehensive review of both trials comparing them and focusing on their differences.

Background: Transcatheter mitral valve repair (TMVR) could improve survival in functional mitral regurgitation (FMR), but it is necessary to consider the influence of left ventricular ejection fraction (LVEF). Therefore, we compare the outcomes after TMVR with Mitraclip&reg, between two groups according to LVEF. Methods: In an observational registry study, we compared the outcomes in patients with FMR who underwent TMVR with and without LVEF &lt, 30%. The primary endpoint was the combined one-year all-cause mortality and unplanned hospital readmissions due to HF. The secondary end-points were New York Heart Association (NYHA) functional class and mitral regurgitation (MR) severity. Propensity-score matching was used to create two groups with the same baseline characteristics, except for baseline LVEF. Results: Among 535 FMR eligible patients, 144 patients with LVEF &lt, 30% (group 1) and 144 with LVEF &gt, 30% (group 2) had similar propensity scores and were included in the analyses. The primary study endpoint was significantlly higher in group 1 (33.3% vs. 9.4%, p = 0.002). There was a maintained improvement in secondary endpoints without significant differences among groups. Conclusion: FMR patients with LVEF &lt, 30% treated with MitraClip&reg, had higher mortality and readmissions than patients with LVEF &ge, 30% treated with the same device. However, both groups improved the NYHA functional class and MR severity.

INTRODUCTION AND OBJECTIVES In the last few decades, there has been a continuous process of improvement in medical treatment and secondary prevention measures after ST-segment elevation myocardial infarction (STEMI). Patients older than 65 years are at increased risk of death due to this event. Our aim was to determine whether patients aged less than 65 years and 65 years and older experiencing a STEMI can recover a life expectancy similar to that of the general population of the same age, sex, and geographical region. METHODS We included all patients experiencing a STEMI at our institution during a 6-year period in an observational-study (SurviSTEMI: survival in STEMI). We calculated their observed survival, expected survival, and excess mortality. We repeated all analyses for survivors of the acute event stratifying by 65 years. RESULTS For patients aged

The interleukin-17 (IL-17) pathway would play an important role in the pathogenesis of atherosclerosis and coronary-artery disease (CAD). The IL-17 inflammatory mediators are expressed by Th17 cells, a group of CD4 + leukocytes that infiltrate the vascular milieu and are pivotal in the origin, progression, stability and rupture of the atherosclerotic lesion. Cigarette smoke compounds stimulated the expression of IL-17 and IL-17-receptors. In atherogenic mice models the deficiency of IL-17RA resulted in a reduction of the atherosclerotic lesion size and leukocyte infiltrate. We hypothesised that common the IL-17RA transcript might be differential expressed in the leukocytes from CAD patients and healthy individuals.The relative amount of the IL-17RA to ACTB transcript was determined in total leukocytes of 55 patients and 50 controls, all smokers. We genotyped the IL-17RA rs48195554 promoter polymorphisms in 390 healthy controls and 450 early-onset CAD patients.Patients showed significantly higher mean IL-17RA normalised transcript value than controls (p 0.001). For the IL-17RA rs48195554 promoter polymorphisms, IL-17RA G-carriers showed higher transcript values. However, allele and genotype frequencies did not differ between patients and controls and we thus excluded a significant association with CAD.The higher levels of the IL-17RA transcript among CAD-patients was in agreement with a role for the IL-17 pathway in the pathogenesis of coronary atherosclerosis.

Background The main objective of this study was to evaluate one-year clinical outcome of patients with symptomatic mitral regurgitation (MR) treated with transcatheter mitral valve repair (TMVR) according to the etiology of MR. Methods Data from a single high-volume center of all consecutive cases with symptomatic MR undergoing TMVR where prospectively included and followed. Results Between October 2015 and October 2019, 81 consecutive patients underwent TMVR and were included in the investigation. The mean age was 75.73±7.81 years, 55 (67.9%) were male. The most frequent mechanism was functional MR (FMR) (59%). The mean EuroSCORE II was 5.7±4.94 [FMR 5.38±3.9, degenerative MR (DMR) 5.72±4.7 and mixed MR (MMR) 6.6±7.5; P=0.7776] and STS score mean was 5.21±3.31 (FMR 4.6±2.3, DMR 6.43±5.2 and MMR 5.7±3.2; P=0.126). Patients with FMR had higher rates of dilated (36 patients, 75.5%) and ischemic (15 patients, 31.3%) cardiomyopathy, as well as worse left ventricular ejection fraction (LVEF). Procedural success was achieved in 72 (88.9%) patients, with a similar distribution between groups. The median of follow-up was 16.3 months. The primary combined endpoint occurred in 19 (23.5%) cases. The number of the combined event regarding the different etiologies were 15 (31.2%) in FMR, 2 (11.8%) in DMR and 5 (31.3%) in MMR (P=0.276). Sixteen patients (20.0%) died during the first year of follow-up and 19 (23.5%) had unplanned heart failure (HF) hospitalization. Previous surgical revascularization (HR =4.94, P=0.004) and a redo TMVR (HR =11.3, P=0.006) predicted the main event. Conclusions TMVR with the Mitraclip device is safe, with a low incidence of complications and a high rate of procedural success. One-year outcomes show reduction of all cause death and HF admissions. Moreover, most of the patients have sustained MR reduction and an improvement in the functional class at the end of follow-up.

Resumen La miocardiopatia no compactada es una entidad heterogenea y compleja de la que existen todavia muchas dudas por resolver. Mientras que la American Heart Association la incluye entre las miocardiopatias de origen genetico, la Sociedad Europea de Cardiologia la considera como una miocardiopatia no clasificada. Puede presentarse tanto de forma esporadica como familiar, aislada o asociada con otras cardiopatias, afectar solo al ventriculo izquierdo o a ambos y puede, en ocasiones, aparecer como un fenotipo mixto en pacientes con otras miocardiopatias. A sus diferentes manifestaciones morfologicas se asocian tambien diferentes formas de presentacion clinica e, incluso, la no compactacion del ventriculo izquierdo puede estar desencadenada por otros procesos fisiologicos o patologicos. El objeto de esta revision es una puesta al dia de esta entidad y de sus controversias.

Patients with solid-organ transplants usually present at the emergency department with nonspecific symptoms. The physician should consider a great variety of syndromes and diseases, given the greater risk that solid-organ transplant patients carry because of immunosuppression and transplant-related conditions. Myocardial infarction caused by cardiac allograft vasculopathy must be always suspected and ruled out, even when initial symptoms do not orientate in that direction. We present a case that conjugates signs that can be present in different pathologies. It shows that fever is not always related to infection or rejection but could also appear in acute cardiac allograft vasculopathy. It emphasizes the need of a multi-disciplinary team led by a heart transplant specialist when dealing with this sort of clinical case.

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: Coronary artery disease (CAD) is the most frequent cause of ST-segment elevation myocardial infarction (STEMI). Etiopathogenic and prognostic characteristics in young patients may differ from older patients and young women may present worse outcomes than men. We aimed to evaluate the clinical characteristics and prognosis of men and women with premature STEMI. Methods: A total 1404 consecutive patients were referred to our institution for emergency cardiac catheterization due to STEMI suspicion (1 January 2014–31 December 2018). Patients with confirmed premature (&lt, 55 years old in men and &lt, 60 in women) STEMI (366 patients, 83% men and 17% women) were included (359 atherothrombotic and 7 spontaneous coronary artery dissection (SCAD)). Results: Premature STEMI patients had a high prevalence of classical cardiovascular risk factors. Mean follow-up was 4.1 years (±1.75 SD). Mortality rates, re-hospitalization, and hospital stay showed no significant differences between sexes. More than 10% of women with premature STEMI suffered SCAD. There were no significant differences between sexes, neither among cholesterol levels nor in hypolipemiant therapy. The global survival rates were similar to that expected in the general population of the same sex and age in our region with a significantly higher excess of mortality at 6 years among men compared with the general population. Conclusion: Our results showed a high incidence of cardiovascular risk factors, a high prevalence of SCAD among young women, and a generally good prognosis after standardized treatment. During follow-up, 23% suffered a major cardiovascular event (MACE), without significant differences between sexes and observed survival at 1, 3, and 6 years of follow-up was 96.57% (95% CI 94.04–98.04), 95.64% (95% CI 92.87–97.35), and 94.5% (95% CI 91.12–97.66). An extra effort to prevent/delay STEMI should be invested focusing on smoking avoidance and optimal hypolipemiant treatment both in primary and secondary prevention.

Background: Long QT syndrome (LQTS) is an inheritable arrhythmogenic disorder associated with life-threatening arrhythmic events (LAEs). In general, patients with LQTS2 (KCNH2) and LQTS3 (SCN5A) are considered to be a greater risk of LAEs than LQTS1 (KCNQ1) patients. Gender differences are also important. Series analyzing families with the same pathogenic variants may help in the progress of elaborating strong specific genotype-phenotype management strategies. In this manuscript, we describe the phenotype of seven unrelated families, carriers of the KCNQ1 G168R pathogenic variant. Methods: we identified all consecutive index cases referred for genetic testing with LQTS diagnosis carriers of KCNQ1 G168R variant. Genetic and clinical screening for all available relatives was performed. Results: we evaluated seven unrelated families, with a total 34 KCNQ1 G168R carriers (two obligated carriers died without available EKGs to evaluate the phenotype). All index cases but one were women and three of them presented with aborted sudden cardiac death (SCD) or syncope. The presence of sudden death in these families is notable, with a total of nine unexplained sudden deaths and four aborted SCD. Phenotype penetrance was 100% in women and 37.5% in men. Conclusions: KCNQ1 G168R is a pathogenic variant, with a high penetrance among women and mild penetrance among men. Risk for LAEs in this variant seems not negligible, especially among woman, and risk stratification should always be carefully evaluated.

Background The durability of aortic valve bioprosthesis and the structural valve deterioration (SVD) are could be treated with valve-in-valve (VIV) transcatheter aortic valve implantation (TAVI). This technique has been proven to be a feasible procedure with good results in selected patients. The aim of this work was to assess the long-term results of this TAVI with an autoexpandable valve in patients with failed Mitroflow (MF) bioprosthetic aortic valves. Methods Single center, observational and prospective study that included 65 consecutive patients with symptomatic failed MF bioprosthetic aortic valve, treated with VIV-TAVI. The primary endpoints were clinical long-term events including all-cause mortality, cardiovascular mortality, re-hospitalization due to heart failure, stroke/transient ischemic attack (TIA) and endocarditis. Secondary endpoints were the absence of SVD or patient-prosthesis mismatch (PPM) and valve hemodynamics analysis at follow-up. Results Between March 2012 to July 2019, 65 symptomatic patients (age 80.4±5.9 years) with degenerated MF valves (numbers 19: 27.7%; 21: 38.5%; 23: 21.5%; 25: 12.3%) underwent CoreValve (n=11) or Evolut R (n=54) implantation (23, 26 and 29 mm sizes). The STS predicted risk of mortality was 6.39%±5.62%. The primary combined endpoint occurred in 32.3% of the cases. A total of 13 patients (20%) died during follow-up, but 4 (7.3%) from cardiovascular causes. Two patients were reported of having a stroke/TIA and 5 readmissions for cardiovascular causes were reported (2 of them within the first 30 days). Twenty-five patients (38.5%) presented PPM during follow-up, being PPM severe in 15 (23.1%). Conclusions Self-expanding TAVI for degenerated MF bioprosthesis has favourable long-term outcomes. It is a good option in order to avoid the risks of redo surgery in selected patients.

BACKGROUND: Mitral regurgitation (MR) is one of the most prevalent valvular diseases in our society. Transcatheter mitral valve repair (TMVR) with the MitraClip(®) system is increasingly used for treating this condition. The aim of our study is to analyse morphological mitral valve changes related to the procedure and its correlation with the degree of regurgitation at mid-term follow-up and with the combined endpoint of heart failure and all-cause mortality. METHODS: A single-centre, prospective and observational study including consecutive patients admitted between October 2015 and October 2019 for TMVR was designed. The mitral valve annulus (MVA) was analyzed using the three-dimensional MVQ QLAB mitral valve quantification software (Philips; Amsterdam, The Netherlands). Clinical data was collected retrospectively. RESULTS: Eighty-two MitraClip(®) were implanted. Control echocardiograms showed a significant decrease in the three measures: annular diameters, perimeter and area. Patients with functional MR had greater left ventricular and mitral annular dimensions and experienced greater reductions in anteroposterior diameter and mitral valve area compared with organic MR patients. The anteroposterior diameter reduction (OR 0.90; 95% CI: 0.82–0.99), as well as posterior leaflet grasping (OR 0.94; 95% CI: 0.89–0.99) were associated with the probability of significant MR recurrence. Posterior leaflet grasping and left ventricle ejection fraction were associated with the combined endpoint of heart failure and any cause death. CONCLUSIONS: MitraClip(®) implantation results in secondary changes in the mitral annular morphology. The magnitude of these morphological changes varies depending on the etiology of the mitral valve regurgitation. Posterior leaflet grasping and anteroposterior diameter reduction after clip are factors associated with relevant clinical and echocardiographic endpoints.

BACKGROUND: Functional mitral regurgitation (FMR) is a bad prognosis condition despite optimal medical treatment. Nowadays there is an open debate about the surgical versus percutaneous treatment. The main objective of this study is to evaluate the mid-term follow up clinical outcomes of patients with FMR treated with MitraClip(®) system, according to their left ventricular ejection fraction (LVEF). METHODS: Data was obtained from two experienced centers in transcatheter mitral valve repair (TMVR). All consecutive cases of severe FMR undergoing TMVR in both centers with the same inclusion criteria were included prospectively in this study and followed-up. Periodical follow-ups with clinical and echocardiographic evaluation were scheduled from the baseline procedure, at 3 months and then yearly. RESULTS: From October 2015 to October 2019, a total of 119 patients with FMR at 2 centers in Spain underwent TMVR with the MitraClip(®) procedure and were included in this study. The mean age was 73.8±8.9 years old and 32 patients (26.9%) were female. A 39.5% of cases [47] had a LVEF ≤30% (group 1) and 60.5% (72 cases) had a LVEF >30% (group 2). There was a similar distribution in cardiovascular risk factors, age and other diseases. All MitraClip(®) implantations were elective and procedural success was achieved in 110 patients (92.4%) with a similar distribution between the groups. There were no differences in procedural time and the number of implanted clips. The median follow-up was 22.6 months (IQR, 11.43–34.98 months). The primary combined endpoint occurred in the 41.6% of the global cohort, 57.5% in group 1 and 30.99% in group 2 (P=0.036). LVEF was associated to the main event in the multivariate analysis (HR 2.09, 95% CI: 1.12–3.89; P=0.02). CONCLUSIONS: The MitraClip edge-to-edge technique is a safe and effective procedure for the treatment of FMR. In this study, patients with LVEF >30% treated with Mitraclip presented better clinical cardiovascular outcomes than those with a LVEF ≤30%. Regardless clinical outcomes, at the end of the follow-up, there was a sustained reduction in MR grades and an important improvement in NYHA functional class.

Functional mitral regurgitation (MR) could be defined as a ventricular disease where mitral valve is structurally normal, left chambers are enlarged and mitral annulus is dilated with lack of coaptation of leaflets. Transcatheter mitral valve repair technique has broadened the therapeutic range in the treatment of severe MR. The aim of this study was to review outcomes of MitraClip vs. medical treatment for functional MR. We also planned to review the concept of functional MR, assessment of the degree, prognosis and therapy options. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Medline through PubMed database was used to search. The present review included manuscripts published between January 2009 and September 2019. Two authors independently screened titles and abstracts of all publications, and performed the selection of studies and data extraction. In the case of disagreements, consensus meetings reached the final decision. Inclusion criteria were: (I) randomized controlled trials and (II) works must compare MitraClip versus optimal medical treatment. Transcatheter mitral valve repair along optimal medical treatment has been compared with optimal medical therapy in two different randomized trials. In the COAPT trial, the MitraClip group showed a significant reduction in mortality and heart failure (HF) hospitalizations. In the MITRA-FR trial, no significant differences were observed between both groups. We reviewed important aspects of functional MR and performed a comprehensive review of both trials comparing them and focusing on their differences.

Non-compaction cardiomyopathy is a heterogeneous and complex entity concerning which there are still many doubts to be resolved. While the American Heart Association includes it among genetic cardiomyopathies, the European Society of Cardiology treats it as an unclassified cardiomyopathy. It may present in a sporadic or familial form, isolated or associated with other heart diseases, affecting only the left ventricle or both and can sometimes appear as a mixed phenotype in patients with other cardiomyopathies. Different forms of clinical presentation are also associated with its different morphological manifestations, and even non-compaction of the left ventricle may be triggered by other physiological or pathological processes. The purpose of this review is an update of this entity and its controversies.

Introduction and objectives Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. The current challenge relies on the accurate classification of the pathogenicity of the variants. Transthoracic echocardiography (TTE) is recommended at initial evaluation and cardiac magnetic resonance (CMR) imaging should also be considered. We aimed to reappraise the penetrance and clinical expression of the MYBPC3 p.G263* variant. Methods Three hundred and eighty-four HCM probands and a control cohort of 450 individuals were studied for the main sarcomere genes by next-generation sequencing. All MYBPC3 p.G263* carriers were identified and family screening was performed. Clinical information was recorded retrospectively before 2015 and prospectively thereafter. Extra effort was invested in performing CMR in all carriers, despite TTE results. Results Thirteen HCM probands and none of the controls were carriers of the MYBPC3 p.G263* pathogenic variant (according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology). A total of 39 carriers were identified with family screening. Most patients with HCM were asymptomatic at the time of diagnosis and showed late-onset disease. Despite having a relatively benign course in the young, late HCM-related complications could occur. Penetrance was around 70% when evaluated by TTE and was 87.2% with TTE plus CMR. Penetrance was age-dependent, reaching 100% in carriers older than 55 years. Conclusions MYBPC3 p.G263* shares with most truncating pathogenic variants in this gene a late onset, relatively benign clinical course in the young, and high penetrance. Cardiac magnetic resonance could be a useful tool to evaluate carriers despite TTE results.

Interventricular septal hematoma is a rare but potentially dangerous complication of retrograde chronic total occlusion (CTO) percutaneous coronary interventions (PCI) [(1,2)][1]. A 58-year-old man was referred for right coronary artery CTO-PCI performed by a retrograde approach via the collateral

Bicuspid aortic valve (BAV) or bicuspid aortopathy is the most common congenital heart disease. It can be clinically silent and it is often identified as an incidental finding in otherwise healthy, asymptomatic patients. However, it can be dysfunctioning at birth, even requiring neonatal intervention, or, in time, lead to aortic stenosis, aortic insufficiency, and endocarditis, and also be associated with aortic aneurysm and aortic dissection. Given its prevalence and significant complications, it is estimated that BAV is responsible for more deaths and morbidity than the combined effects of all the other congenital heart defects. Pathology of BAV is still not well known and many questions are unresolved. In this manuscript we review some aspects on bicuspid aortopathy, a heterogeneous and frequent disease in which like some authors have previously described, complex gene environment are present. Further investigations and, what is more, multidisciplinary teams are needed to improve our knowledge on this really fascinating disease.