ST-segment elevation myocardial infarction (STEMI) networks should guarantee STEMI care with good clinical results and within the recommended time parameters. There is no contemporary information on the performance of these networks in Spain. The objective of this study was to analyze the clinical characteristics of patients, times to reperfusion, characteristics of the intervention performed, and 30-day mortality.Prospective, observational, multicenter registry of consecutive patients treated in 17 STEMI networks in Spain (83 centers with the Infarction Code), between April 1 and June 30, 2019.A total of 5401 patients were attended (mean age, 64 ± 13 years; 76.9% male), of which 4366 (80.8%) had confirmed STEMI. Of these, 87.5% were treated with primary angioplasty, 4.4% with fibrinolysis, and 8.1% did not receive reperfusion. In patients treated with primary angioplasty, the time between symptom onset and reperfusion was 193 [135-315] minutes and the time between first medical contact and reperfusion was 107 [80-146] minutes. Overall 30-day mortality due to STEMI was 7.9%, while mortality in patients treated with primary angioplasty was 6.8%.Most patients with STEMI were treated with primary angioplasty. In more than half of the patients, the time from first medical contact to reperfusion was < 120 minutes. Mortality at 30 days was relatively low.Las redes de Código Infarto deben garantizar una atención al infarto agudo de miocardio con elevación del segmento ST con buenos resultados clínicos y dentro de los parámetros de tiempo recomendados. No hay información contemporánea sobre el funcionamiento de estas redes en España. El objetivo es analizar las características clínicas de los pacientes atendidos, el tiempo hasta la reperfusión, las características de la intervención realizada y la mortalidad a 30 días.Registro prospectivo, observacional y multicéntrico de pacientes los consecutivos atendidos en 17 redes de Código Infarto en España (83 centros con Código Infarto) entre el 1 de abril y el 30 de junio de 2019.Se atendió a 5.401 pacientes (media de edad, 64 ± 13 años; el 76,9% varones), de los que 4.366 (80,8%) sufrieron un infarto con elevación del ST. De estos, se trató al 87,5% con angioplastia primaria, al 4,4% con fibrinolisis y al 8,1% sin reperfusión. En los casos tratados con angioplastia primaria, el tiempo entre el inicio de los síntomas y la reperfusión fue 193 [135-315] min y el tiempo entre el primer contacto médico y la reperfusión, 107 [80-146] min. La mortalidad total a 30 días por infarto agudo de miocardio con elevación del ST fue del 7,9%, mientras que entre los pacientes tratados con angioplastia primaria fue del 6,8%.Se trató con angioplastia primaria a la inmensa mayoría de los pacientes con infarto agudo de miocardio con elevación del ST, y en más de la mitad de los casos el tiempo desde el primer contacto médico hasta la reperfusión fue < 120 min. La mortalidad a 30 días fue relativamente baja.

Las redes de Código Infarto deben garantizar una atención al infarto agudo de miocardio con elevación del segmento ST con buenos resultados clínicos y dentro de los parámetros de tiempo recomendados. No hay información contemporánea sobre el funcionamiento de estas redes en España. El objetivo es analizar las características clínicas de los pacientes atendidos, el tiempo hasta la reperfusión, las características de la intervención realizada y la mortalidad a 30 días.Registro prospectivo, observacional y multicéntrico de pacientes los consecutivos atendidos en 17 redes de Código Infarto en España (83 centros con Código Infarto) entre el 1 de abril y el 30 de junio de 2019.Se atendió a 5.401 pacientes (media de edad, 64 ± 13 años; el 76,9% varones), de los que 4.366 (80,8%) sufrieron un infarto con elevación del ST. De estos, se trató al 87,5% con angioplastia primaria, al 4,4% con fibrinolisis y al 8,1% sin reperfusión. En los casos tratados con angioplastia primaria, el tiempo entre el inicio de los síntomas y la reperfusión fue 193 [135-315] min y el tiempo entre el primer contacto médico y la reperfusión, 107 [80-146] min. La mortalidad total a 30 días por infarto agudo de miocardio con elevación del ST fue del 7,9%, mientras que entre los pacientes tratados con angioplastia primaria fue del 6,8%.Se trató con angioplastia primaria a la inmensa mayoría de los pacientes con infarto agudo de miocardio con elevación del ST, y en más de la mitad de los casos el tiempo desde el primer contacto médico hasta la reperfusión fue < 120 min. La mortalidad a 30 días fue relativamente baja.ST-segment elevation myocardial infarction (STEMI) networks should guarantee STEMI care with good clinical results and within the recommended time parameters. There is no contemporary information on the performance of these networks in Spain. The objective of this study was to analyze the clinical characteristics of patients, times to reperfusion, characteristics of the intervention performed, and 30-day mortality.Prospective, observational, multicenter registry of consecutive patients treated in 17 STEMI networks in Spain (83 centers with the Infarction Code), between April 1 and June 30, 2019.A total of 5401 patients were attended (mean age, 64 ± 13 years; 76.9% male), of which 4366 (80.8%) had confirmed STEMI. Of these, 87.5% were treated with primary angioplasty, 4.4% with fibrinolysis, and 8.1% did not receive reperfusion. In patients treated with primary angioplasty, the time between symptom onset and reperfusion was 193 [135-315] minutes and the time between first medical contact and reperfusion was 107 [80-146] minutes. Overall 30-day mortality due to STEMI was 7.9%, while mortality in patients treated with primary angioplasty was 6.8%.Most patients with STEMI were treated with primary angioplasty. In more than half of the patients, the time from first medical contact to reperfusion was < 120 minutes. Mortality at 30 days was relatively low.Full English text available from:www.revespcardiol.org/en

Importance Truncating variants in the gene encoding filamin C (FLNCtv) are associated with arrhythmogenic and dilated cardiomyopathies with a reportedly high risk of ventricular arrhythmia. Objective To determine the frequency of and risk factors associated with adverse events among FLNCtv carriers compared with individuals carrying TTN truncating variants (TTNtv). Design, Setting, and Participants This cohort study recruited 167 consecutive FLNCtv carriers and a control cohort of 244 patients with TTNtv matched for left ventricular ejection fraction (LVEF) from 19 European cardiomyopathy referral units between 1990 and 2018. Data analyses were conducted between June and October, 2020. Main Outcomes and Measures The primary end point was a composite of malignant ventricular arrhythmia (MVA) (sudden cardiac death, aborted sudden cardiac death, appropriate implantable cardioverter-defibrillator shock, and sustained ventricular tachycardia) and end-stage heart failure (heart transplant or mortality associated with end-stage heart failure). The secondary end point comprised MVA events only. Results In total, 167 patients with FLNCtv were studied (55 probands [33%]; 89 men [53%]; mean [SD] age at baseline evaluation, 43 [18] years). For a median follow-up of 20 months (interquartile range, 7-60 months), 29 patients (17.4%) reached the primary end point (19 patients with MVA and 10 patients with end-stage heart failure). Eight (44%) arrhythmic events occurred among individuals with baseline mild to moderate left ventricular systolic dysfunction (LVSD) (LVEF = 36%-49%). Univariable risk factors associated with the primary end point included proband status, LVEF decrement per 10%, ventricular ectopy (≥500 in 24 hours) and myocardial fibrosis detected on cardiac magnetic resonance imaging. The LVEF decrement (hazard ratio [HR] per 10%, 1.83 [95% CI, 1.30-2.57]; P < .001) and proband status (HR, 3.18 [95% CI, 1.12-9.04]; P = .03) remained independent risk factors on multivariable analysis (excluding myocardial fibrosis and ventricular ectopy owing to case censoring). There was no difference in freedom from MVA between FLNCtv carriers with mild to moderate or severe (LVEF ≤35%) LVSD (HR, 1.29 [95% CI, 0.45-3.72]; P = .64). Carriers of FLNCtv with impaired LVEF at baseline evaluation (n = 69) had reduced freedom from MVA compared with 244 TTNtv carriers with similar baseline LVEF (for mild to moderate LVSD: HR, 16.41 [95% CI, 3.45-78.11]; P < .001; for severe LVSD: HR, 2.47 [95% CI, 1.04-5.87]; P = .03). Conclusions and Relevance The high frequency of MVA among patients with FLNCtv with mild to moderate LVSD suggests that higher LVEF values than those currently recommended should be considered for prophylactic implantable cardioverter-defibrillator therapy in FLNCtv carriers.

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, p<0.001). MYBPC3 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 (p<0.05 for both). Nevertheless, the rate of major adverse outcomes was similar between the two groups.ConclusionsMYBPC3 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 BAG3 (BLC2-associated athanogene 3) gene codes for an antiapoptotic protein located on the sarcomere Z-disc. Mutations in BAG3 are associated with dilated cardiomyopathy (DCM), but only a small number of cases have been reported to date, and the natural history of BAG3 cardiomyopathy is poorly understood. OBJECTIVES:This study sought to describe the phenotype and prognosis of BAG3 mutations in a large multicenter DCM cohort. METHODS:The study cohort comprised 129 individuals with a BAG3 mutation (62% males, 35.1 ± 15.0 years of age) followed at 18 European centers. Localization of BAG3 in cardiac tissue was analyzed in patients with truncating BAG3 mutations using immunohistochemistry. RESULTS:At first evaluation, 57.4% of patients had DCM. After a median follow-up of 38 months (interquartile range: 7 to 95 months), 68.4% of patients had DCM and 26.1% who were initially phenotype-negative developed DCM. Disease penetrance in individuals >40 years of age was 80% at last evaluation, and there was a trend towards an earlier onset of DCM in men (age 34.6 ± 13.2 years vs. 40.7 ± 12.2 years; p = 0.053). The incidence of adverse cardiac events (death, left ventricular assist device, heart transplantation, and sustained ventricular arrhythmia) was 5.1% per year among individuals with DCM. Male sex, decreased left ventricular ejection fraction. and increased left ventricular end-diastolic diameter were associated with adverse cardiac events. Myocardial tissue from patients with a BAG3 mutation showed myofibril disarray and a relocation of BAG3 protein in the sarcomeric Z-disc. CONCLUSIONS:DCM caused by mutations in BAG3 is characterized by high penetrance in carriers >40 years of age and a high risk of progressive heart failure. Male sex, decreased left ventricular ejection fraction, and enlarged left ventricular end-diastolic diameter are associated with adverse outcomes in patients with BAG3 mutations.

IntroductionHypertrophic cardiomyopathy (HCM) is the most prevalent inherited heart disease. Next-generation sequencing (NGS) is the preferred genetic test, but the diagnostic value of screening for minor and candidate genes, and the role of copy number variants (CNVs) deserves further evaluation.MethodsThree hundred and eighty-seven consecutive unrelated patients with HCM were screened for genetic variants in the 5 most frequent genes (MYBPC3, MYH7, TNNT2, TNNI3 and TPM1) using Sanger sequencing (N = 84) or NGS (N = 303). In the NGS cohort we analyzed 20 additional minor or candidate genes, and applied a proprietary bioinformatics algorithm for detecting CNVs. Additionally, the rate and classification of TTN variants in HCM were compared with 427 patients without structural heart disease.ResultsThe percentage of patients with pathogenic/likely pathogenic (P/LP) variants in the main genes was 33.3%, without significant differences between the Sanger sequencing and NGS cohorts. The screening for 20 additional genes revealed LP variants in ACTC1, MYL2, MYL3, TNNC1, GLA and PRKAG2 in 12 patients. This approach resulted in more inconclusive tests (36.0% vs. 9.6%, p<0.001), mostly due to variants of unknown significance (VUS) in TTN. The detection rate of rare variants in TTN was not significantly different to that found in the group of patients without structural heart disease. In the NGS cohort, 4 patients (1.3%) had pathogenic CNVs: 2 deletions in MYBPC3 and 2 deletions involving the complete coding region of PLN.ConclusionsA small percentage of HCM cases without point mutations in the 5 main genes are explained by P/LP variants in minor or candidate genes and CNVs. Screening for variants in TTN in HCM patients drastically increases the number of inconclusive tests, and shows a rate of VUS that is similar to patients without structural heart disease, suggesting that this gene should not be analyzed for clinical purposes in HCM.

BACKGROUND:Filamin C (encoded by the FLNC gene) is essential for sarcomere attachment to the plasmatic membrane. FLNC mutations have been associated with myofibrillar myopathies, and cardiac involvement has been reported in some carriers. Accordingly, since 2012, the authors have included FLNC in the genetic screening of patients with inherited cardiomyopathies and sudden death. OBJECTIVES:The aim of this study was to demonstrate the association between truncating mutations in FLNC and the development of high-risk dilated and arrhythmogenic cardiomyopathies. METHODS:FLNC was studied using next-generation sequencing in 2,877 patients with inherited cardiovascular diseases. A characteristic phenotype was identified in probands with truncating mutations in FLNC. Clinical and genetic evaluation of 28 affected families was performed. Localization of filamin C in cardiac tissue was analyzed in patients with truncating FLNC mutations using immunohistochemistry. RESULTS:Twenty-three truncating mutations were identified in 28 probands previously diagnosed with dilated, arrhythmogenic, or restrictive cardiomyopathies. Truncating FLNC mutations were absent in patients with other phenotypes, including 1,078 patients with hypertrophic cardiomyopathy. Fifty-four mutation carriers were identified among 121 screened relatives. The phenotype consisted of left ventricular dilation (68%), systolic dysfunction (46%), and myocardial fibrosis (67%); inferolateral negative T waves and low QRS voltages on electrocardiography (33%); ventricular arrhythmias (82%); and frequent sudden cardiac death (40 cases in 21 of 28 families). Clinical skeletal myopathy was not observed. Penetrance was >97% in carriers older than 40 years. Truncating mutations in FLNC cosegregated with this phenotype with a dominant inheritance pattern (combined logarithm of the odds score: 9.5). Immunohistochemical staining of myocardial tissue showed no abnormal filamin C aggregates in patients with truncating FLNC mutations. CONCLUSIONS:Truncating mutations in FLNC caused an overlapping phenotype of dilated and left-dominant arrhythmogenic cardiomyopathies complicated by frequent premature sudden death. Prompt implantation of a cardiac defibrillator should be considered in affected patients harboring truncating mutations in FLNC.

BACKGROUND:Dilated cardiomyopathy (DCM) is the most frequent cause of heart transplantation (HTx). The genetic basis of DCM among patients undergoing HTx has been poorly characterized. We sought to determine the genetic basis of familial DCM HTx and to establish the yield of modern next generation sequencing (NGS) technologies in this setting. METHODS:Fifty-two heart-transplanted patients due to familial DCM underwent NGS genetic evaluation with a panel of 126 genes related to cardiac conditions (59 associated with DCM). Genetic variants were initially classified as pathogenic mutations or as variants of uncertain significance (VUS). Final pathogenicity status was determined by familial cosegregation studies. RESULTS:Initially, 24 pathogenic mutations were found in 21 patients (40%); 25 patients (48%) carried 19 VUS and 6 (12%) did not show any genetic variant. Familial evaluation of 220 relatives from 36 of the 46 families with genetic variants confirmed pathogenicity in 14 patients and allowed reclassification of VUS as pathogenic in 17 patients, and as non-pathogenic in 3 cases. At the end of the study, the DCM-causing mutation was identified in 38 patients (73%) and 5 patients (10%) harbored only VUS. No genetic variants were identified in 9 cases (17%). CONCLUSIONS:The genetic spectrum of familial DCM patients undergoing HTx is heterogeneous and involves multiple genes. NGS technology plus detailed familial studies allow identification of causative mutations in the vast majority of familial DCM cases. Detailed familial studies remain critical to determine the pathogenicity of underlying genetic defects in a substantial number of cases.

The use of the StarClose vascular closure device for puncture site hemostasis after therapeutic endovascular interventions performed through the axillary artery under anticoagulant therapy in six patients is reported. Three minor complications, including hematoma, prolonged hemostasis, and pain, occurred in three patients. Based on this limited experience, this method can be used safely for axillary artery puncture site hemostasis after endovascular procedures without significant complications.

Congenital anomalies of the pulmonary veins are rare. Meandering right pulmonary vein, considered a part of the Scimitar syndrome spectrum, is often an incidental finding during chest imaging. We present the case of a 4-year-old girl diagnosed with meandering pulmonary vein, who developed pulmonary hypertensive disease with an aggressive course, in spite of absence of hypoxia or elevated pulmonary wedge pressure.

The distal radial approach was recently introduced with the hope to improve patients' comfort, particularly during left wrist access and maybe to reduce the rate of complications (mainly radial artery occlusion). However up to now, little is known about the real incidence and type of complications related to this access site.We report the case of a left distal radial pseudoaneurysm complicating a successful percutaneous recanalization of a right coronary artery chronic total occlusion with bilateral wrist approach (right radial artery retrograde and left distal radial artery antegrade). This complication was successfully resolved by percutaneous thrombin injection.Our case proves that dTRA is not free from conventional vascular complications and this should be considered during the planning of the best strategy for our patients.

Las nuevas técnicas desarrolladas para el análisis genético nos aportan información sobre las bases genéticas de las distintas miocardiopatías, entre ellas, de la miocardiopatía dilatada familiar. Realizamos esta revisión con el fin de aportar información sobre la utilidad clínica del estudio genético en el manejo de estos pacientes.The new technologies developed for genetic analysis provide information on the genetics basis of the different types of cardiomyopathy, including familial dilated cardiomyopathy. A review is presented with the aim of providing information on the clinical use of the genetic study in the management of these patients.