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BACKGROUND: Sarcoidosis is associated with a poor prognosis. There is a lack of data examining the outcomes and readmission rates of sarcoidosis patients with heart failure (SwHF) and without heart failure (SwoHF). We aimed to compare the impact of non-ischemic heart failure on outcomes and readmissions in these two groups. METHODS: The US Nationwide Readmission Database was queried from 2010 to 2019 for SwHF and SwoHF patients identified using the International Classification of Diseases, 9th and 10th Editions. Those with ischemic heart disease were excluded, and both cohorts were propensity matched for age, gender, and Charlson Comorbidity Index (CCI). Clinical characteristics, length of stay, adjusted healthcare-associated costs, 90-day readmission and mortality were analyzed. RESULTS: We identified 97,961 hospitalized patients (median age 63 years, 37.9% male) with a diagnosis of sarcoidosis (35.9% SwHF vs 64.1% SwoHF). On index admission, heart failure patients had higher prevalences of atrioventricular block (3.3% vs 1.4%, P < .0001), ventricular tachycardia (6.5% vs 1.3%, P < .0001), ventricular fibrillation (0.4% vs 0.1%, P < .0001) and atrial fibrillation (22.1% vs 7.5%, P < .0001). SwHF patients were more likely to be readmitted (hazard ratio 1.28, P < .0001), had higher length of hospital stay (5 vs 4 days, P < .0001), adjusted healthcare-associated costs ($9,667.0 vs $9,087.1, P < .0001) and mortality rates on readmission (5.1% vs 3.8%, P < .0001). Predictors of mortality included heart failure, increasing age, male sex, higher CCI, and liver disease. CONCLUSION: SwHF is associated with higher rates of arrhythmia at index admission, as well as greater hospital cost, readmission and mortality rates compared to those without heart failure.
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Bases de Datos Factuales , Insuficiencia Cardíaca , Readmisión del Paciente , Puntaje de Propensión , Sarcoidosis , Humanos , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/economía , Masculino , Femenino , Persona de Mediana Edad , Readmisión del Paciente/estadística & datos numéricos , Sarcoidosis/complicaciones , Sarcoidosis/mortalidad , Sarcoidosis/epidemiología , Sarcoidosis/economía , Anciano , Estados Unidos/epidemiología , Tiempo de Internación/estadística & datos numéricos , ComorbilidadAsunto(s)
Sistema Cardiovascular , Genética , Humanos , Genómica , Curriculum , Corazón , Genética/educaciónRESUMEN
Out of hospital cardiac arrest (OHCA) outcomes can be improved by strengthening the chain of survival, namely prompt cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED). However, provision of bystander CPR and AED use remains low due to individual patient factors ranging from lack of education to socioeconomic barriers and due to lack of resources such as limited availability of AEDs in the community. Although the impact of health inequalities on survival from OHCA is documented, it is imperative that we identify and implement strategies to improve public health and outcomes from OHCA overall but with a simultaneous emphasis on making care more equitable. Disparities in CPR delivery and AED use in OHCA exist based on factors including sex, education level, socioeconomic status, race and ethnicity, all of which we discuss in this review. Most importantly, we discuss the barriers to AED use, and strategies on how these may be overcome.
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Reanimación Cardiopulmonar , Desfibriladores Implantables , Paro Cardíaco Extrahospitalario , Humanos , Paro Cardíaco Extrahospitalario/terapia , Inequidades en Salud , EtnicidadRESUMEN
OBJECTIVE: To contemporaneously reappraise the incidence-rate, prevalence, and natural history of hypertrophic cardiomyopathy (HCM) in Olmsted County, Minnesota, from 1984 to 2015. PATIENTS AND METHODS: A validated medical-record linkage system collecting information for residents of Olmsted County was used to identify all cases of HCM between January 1, 1984, and December 31, 2015. After adjudication of records from Mayo Clinic and Olmsted Medical Center, data relating to diagnoses and outcomes were abstracted. The calculated incidence rate and prevalence were standardized to the US 1980 White population (age- and sex-adjusted) and compared with a prior study examining the years 1975-1984. RESULTS: Two hundred seventy subjects with HCM were identified. The age- and sex-adjusted incidence rate was 6.6 per 100,000 person-years, and the point prevalence of HCM on January 1, 2016, was 89 per 100,000 population. The incidence rate and point prevalence of HCM on January 1, 2016, standardized to the US 1980 White population (age- and sex-adjusted), were 6.7 (95% CI, 7.1 to 8.8) per 100,000 person-years and 81.5 per 100,000 population, respectively. The incidence rate of HCM increased each decade since the index study. Individuals with HCM had a higher overall standardized mortality rate than the general population with an observed to expected HR of 1.44 (95% CI, 1.21 to 1.71; P<.001) which improved by each decade. CONCLUSION: The incidence and prevalence of HCM are higher than rates reported from a prior study in the same community examining the years 1975-1984, but lower than other study cohorts. The risk of mortality in HCM remains higher than expected, albeit with improvement in rates of mortality observed each decade during the study period.
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Cardiomiopatía Hipertrófica , Humanos , Incidencia , Prevalencia , Minnesota/epidemiología , Cardiomiopatía Hipertrófica/epidemiología , Estudios EpidemiológicosRESUMEN
We report the case of a 50-year-old woman with secondary oxalosis following bowel resection resulting in restrictive cardiomyopathy and a diagnosis of cardiac amyloidosis based on the initial workup. The case documented findings by cardiac magnetic resonance imaging and technetium Tc 99m-labeled pyrophosphate scan in patients with cardiac oxalosis, which can mimic findings in cardiac amyloidosis, expanding the differential diagnosis.
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BACKGROUND: Sudden death is the leading cause of mortality in medically refractory epilepsy. Middle-aged persons with epilepsy (PWE) are under investigated regarding their mortality risk and burden of cardiovascular disease (CVD). METHODS: Using UK Biobank, we identified 7786 (1.6%) participants with diagnoses of epilepsy and 6,171,803 person-years of follow-up (mean 12.30 years, standard deviation 1.74); 566 patients with previous histories of stroke were excluded. The 7220 PWE comprised the study cohort with the remaining 494,676 without epilepsy as the comparator group. Prevalence of CVD was determined using validated diagnostic codes. Cox proportional hazards regression was used to assess all-cause mortality and sudden death risk. RESULTS: Hypertension, coronary artery disease, heart failure, valvular heart disease, and congenital heart disease were more prevalent in PWE. Arrhythmias including atrial fibrillation/flutter (12.2% vs 6.9%; P < 0.01), bradyarrhythmias (7.7% vs 3.5%; P < 0.01), conduction defects (6.1% vs 2.6%; P < 0.01), and ventricular arrhythmias (2.3% vs 1.0%; P < 0.01), as well as cardiac implantable electric devices (4.6% vs 2.0%; P < 0.01) were more prevalent in PWE. PWE had higher adjusted all-cause mortality (hazard ratio [HR], 3.9; 95% confidence interval [CI], 3.01-3.39), and sudden death-specific mortality (HR, 6.65; 95% CI, 4.53-9.77); and were almost 2 years younger at death (68.1 vs 69.8; P < 0.001). CONCLUSIONS: Middle-aged PWE have increased all-cause and sudden death-specific mortality and higher burden of CVD including arrhythmias and heart failure. Further work is required to elucidate mechanisms underlying all-cause mortality and sudden death risk in PWE of middle age, to identify prognostic biomarkers and develop preventative therapies in PWE.
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Enfermedades Cardiovasculares , Epilepsia , Insuficiencia Cardíaca , Persona de Mediana Edad , Humanos , Enfermedades Cardiovasculares/epidemiología , Biobanco del Reino Unido , Bancos de Muestras Biológicas , Factores de Riesgo , Epilepsia/complicaciones , Epilepsia/epidemiología , Muerte Súbita/epidemiología , Muerte Súbita/etiología , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiologíaRESUMEN
Cardiac disease affects the heart non-uniformly. Examples include focal septal or apical hypertrophy with reduced strain in hypertrophic cardiomyopathy, replacement fibrosis with akinesia in an infarct-related coronary artery territory, and a pattern of scarring in dilated cardiomyopathy. The detail and versatility of cardiovascular magnetic resonance (CMR) imaging mean it contains a wealth of information imperceptible to the naked eye and not captured by standard global measures. CMR-derived heterogeneity biomarkers could facilitate early diagnosis, better risk stratification, and a more comprehensive prediction of treatment response. Small cohort and case-control studies demonstrate the feasibility of proof-of-concept structural and functional heterogeneity measures. Detailed radiomic analyses of different CMR sequences using open-source software delineate unique voxel patterns as hallmarks of histopathological changes. Meanwhile, measures of dispersion applied to emerging CMR strain sequences describe variable longitudinal, circumferential, and radial function across the myocardium. Two of the most promising heterogeneity measures are the mean absolute deviation of regional standard deviations on native T1 and T2 and the standard deviation of time to maximum regional radial wall motion, termed the tissue synchronization index in a 16-segment left ventricle model. Real-world limitations include the non-standardization of CMR imaging protocols across different centres and the testing of large numbers of radiomic features in small, inadequately powered patient samples. We, therefore, propose a three-step roadmap to benchmark novel heterogeneity biomarkers, including defining normal reference ranges, statistical modelling against diagnosis and outcomes in large epidemiological studies, and finally, comprehensive internal and external validations.
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Cardiomiopatía Hipertrófica , Imagen por Resonancia Magnética , Humanos , Miocardio/patología , Cardiomiopatía Hipertrófica/patología , Espectroscopía de Resonancia Magnética , Medición de Riesgo , Biomarcadores , Imagen por Resonancia Cinemagnética/métodos , Valor Predictivo de las Pruebas , Función Ventricular IzquierdaRESUMEN
BACKGROUND: As the availability of genomic testing grows, variant interpretation will increasingly be performed by genomic generalists, rather than domain-specific experts. Demand is rising for laboratories to accurately classify variants in inherited cardiac condition (ICC) genes, including secondary findings. METHODS: We analyse evidence for inheritance patterns, allelic requirement, disease mechanism and disease-relevant variant classes for 65 ClinGen-curated ICC gene-disease pairs. We present this information for the first time in a structured dataset, CardiacG2P, and assess application in genomic variant filtering. RESULTS: For 36/65 gene-disease pairs, loss of function is not an established disease mechanism, and protein truncating variants are not known to be pathogenic. Using the CardiacG2P dataset as an initial variant filter allows for efficient variant prioritisation whilst maintaining a high sensitivity for retaining pathogenic variants compared with two other variant filtering approaches. CONCLUSIONS: Access to evidence-based structured data representing disease mechanism and allelic requirement aids variant filtering and analysis and is a pre-requisite for scalable genomic testing.
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Pruebas Genéticas , Variación Genética , Humanos , Bases de Datos Genéticas , Genómica , Patrón de HerenciaRESUMEN
BACKGROUND: Inherited cardiomyopathies present with broad variation of phenotype. Data are limited regarding genetic screening strategies and outcomes associated with predicted deleterious variants in cardiomyopathy-associated genes in the general population. OBJECTIVES: The authors aimed to determine the risk of mortality and composite cardiomyopathy-related outcomes associated with predicted deleterious variants in cardiomyopathy-associated genes in the UK Biobank. METHODS: Using whole exome sequencing data, variants in dilated, hypertrophic, and arrhythmogenic right ventricular cardiomyopathy-associated genes with at least moderate evidence of disease causality according to ClinGen Expert Panel curations were annotated using REVEL (≥0.65) and ANNOVAR (predicted loss-of-function) considering gene-disease mechanisms. Genotype-positive and genotype-negative groups were compared using time-to-event analyses for the primary (all-cause mortality) and secondary outcomes (diagnosis of cardiomyopathy; composite outcome of diagnosis of cardiomyopathy, heart failure, arrhythmia, stroke, and death). RESULTS: Among 200,619 participants (age at recruitment 56.46 ± 8.1 years), 5,292 (2.64%) were found to host ≥1 predicted deleterious variants in cardiomyopathy-associated genes (CMP-G+). After adjusting for age and sex, CMP-G+ individuals had higher risk for all-cause mortality (HR: 1.13 [95% CI: 1.01-1.25]; P = 0.027), increased risk for being diagnosed with cardiomyopathy later in life (HR: 5.75 [95% CI: 4.58-7.23]; P < 0.0001), and elevated risk for composite outcome (HR: 1.29 [95% CI: 1.20-1.39]; P < 0.0001) than CMP-G- individuals. The higher risk for being diagnosed with cardiomyopathy and composite outcomes in the genotype-positive subjects remained consistent across all cardiomyopathy subgroups. CONCLUSIONS: Adults with predicted deleterious variants in cardiomyopathy-associated genes exhibited a slightly higher risk of mortality and a significantly increased risk of developing cardiomyopathy, and cardiomyopathy-related composite outcomes, in comparison with genotype-negative controls.
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Mitral valve prolapse (MVP) is a heart valve disease that is often familial, affecting 2%-3% of the general population. MVP with or without mitral regurgitation can be associated with an increased risk of ventricular arrhythmias and sudden cardiac death (SCD). Research on familial MVP has specifically focused on genetic factors, which may explain the heritable component of the disease estimated to be present in 20%-35%. Furthermore, the structural and electrophysiological substrates underlying SCD/ventricular arrhythmia risk in MVP have been studied postmortem and in the electrophysiology laboratory, respectively. Understanding how familial MVP and rhythm disorders are related may help patients with MVP by individualizing risk and working to develop effective management strategies. This contemporary, state-of-the-art, expert review focuses on genetic factors and familial components that underlie MVP and arrhythmia and encapsulates clinical, genetic, and electrophysiological issues that should be the objectives of future research.
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Cardiomiopatías , Humanos , Volumen Sistólico , Valor Predictivo de las Pruebas , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/patología , Muerte Súbita , Espectroscopía de Resonancia Magnética , Medición de Riesgo , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Función Ventricular IzquierdaRESUMEN
BACKGROUND: With genetic testing advancements, the burden of incidentally identified cardiac disease-associated gene variants is rising. These variants may carry a risk of sudden cardiac death, highlighting the need for accurate diagnostic interpretation. We sought to identify pathogenic hotspots in sudden cardiac death-associated genes using amino acid-level signal-to-noise (S:N) analysis and develop a web-based precision medicine tool, DiscoVari, to improve variant evaluation. METHODS: The minor allele frequency of putatively pathogenic variants was derived from cohort-based cardiomyopathy and channelopathy studies in the literature. We normalized disease-associated minor allele frequencies to rare variants in an ostensibly healthy population (Genome Aggregation Database) to calculate amino acid-level S:N. Amino acids with S:N above the gene-specific threshold were defined as hotspots. DiscoVari was built using JavaScript ES6 and using open-source JavaScript library ReactJS, web development framework Next.js, and JavaScript runtime NodeJS. We validated the ability of DiscoVari to identify pathogenic variants using variants from ClinVar and individuals clinically evaluated at the Duke University Hospitals with cardiac genetic testing. RESULTS: We developed DiscoVari as an internet-based tool for S:N-based variant hotspots. Upon validation, a higher proportion of ClinVar likely pathogenic/pathogenic variants localized to DiscoVari hotspots (43.1%) than likely benign/benign variants (17.8%; P<0.0001). Further, 75.3% of ClinVar variants reclassified to likely pathogenic/pathogenic were in hotspots, compared with 41.3% of those reclassified as variants of uncertain significance (P<0.0001) and 23.4% of those reclassified as likely benign/benign (P<0.0001). Of the clinical cohort variants, 73.1% of likely pathogenic/pathogenic were in hotspots, compared with 0.0% of likely benign/benign (P<0.01). CONCLUSIONS: DiscoVari reliably identifies disease-susceptible amino acid residues to evaluate variants by searching amino acid-specific S:N ratios.
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Cardiomiopatías , Canalopatías , Humanos , Variación Genética , Canalopatías/genética , Medicina de Precisión , Virulencia , Cardiomiopatías/genética , Muerte Súbita Cardíaca/patología , AminoácidosRESUMEN
BACKGROUND: Fatty liver disease in the absence of excessive alcohol consumption is an increasingly common condition with a global prevalence of ~ 25-30% and is also associated with cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies its pathogenesis, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been proposed for this condition. MAFLD is closely intertwined with obesity, type 2 diabetes mellitus and atherogenic dyslipidemia, which are established cardiovascular risk factors. Unlike CVD, which has received attention in the literature on fatty liver disease, the CVD risk associated with MAFLD is often underestimated, especially among Cardiologists. METHODS AND RESULTS: A multidisciplinary panel of fifty-two international experts comprising Hepatologists, Endocrinologists, Diabetologists, Cardiologists and Family Physicians from six continents (Asia, Europe, North America, South America, Africa and Oceania) participated in a formal Delphi survey and developed consensus statements on the association between MAFLD and the risk of CVD. Statements were developed on different aspects of CVD risk, ranging from epidemiology to mechanisms, screening, and management. CONCULSIONS: The expert panel identified important clinical associations between MAFLD and the risk of CVD that could serve to increase awareness of the adverse metabolic and cardiovascular outcomes of MAFLD. Finally, the expert panel also suggests potential areas for future research.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Hepatopatías , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Asia , ConsensoRESUMEN
Background: As availability of genomic testing grows, variant interpretation will increasingly be performed by genomic generalists, rather than domain-specific experts. Demand is rising for laboratories to accurately classify variants in inherited cardiac condition (ICC) genes, including as secondary findings. Methods: We analyse evidence for inheritance patterns, allelic requirement, disease mechanism and disease-relevant variant classes for 65 ClinGen-curated ICC gene-disease pairs. We present this information for the first time in a structured dataset, CardiacG2P, and assess application in genomic variant filtering. Results: For 36/65 gene-disease pairs, loss-of-function is not an established disease mechanism, and protein truncating variants are not known to be pathogenic. Using CardiacG2P as an initial variant filter allows for efficient variant prioritisation whilst maintaining a high sensitivity for retaining pathogenic variants compared with two other variant filtering approaches. Conclusions: Access to evidence-based structured data representing disease mechanism and allelic requirement aids variant filtering and analysis and is pre-requisite for scalable genomic testing.
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Comparisons of transthoracic echocardiography (TTE) and cardiovascular magnetic resonance (CMR) derived left ventricular ejection fraction (LVEF) have been reported in core-lab settings but are limited in the real-world setting. We retrospectively identified outpatients from 4 hospital sites who had clinically indicated quantitative assessment of LVEFTTE and LVEFCMR and evaluated their concordance. In 767 patients (mean age 47.6 years; 67.9% males) the median inter-modality interval was 35 days. There was significant positive correlation between the 2 modalities (râ¯=â¯0.75; P < 0.001). Median LVEF was 54% (IQR 47%, 60%) for TTE and 59% (IQR 51%, 64%) for CMR, (P < 0.001). Normal LVEFTTE was confirmed by CMR in 90.6% of cases. Of patients with severely impaired LVEFTTE, 42.3% were upwardly reclassified by CMR as less severely impaired. The overall proportion of patients that had their LVEF category confirmed by both imaging modalities was 64.4%; Cohen's Kappa 0.41, indicating fair-to-moderate agreement. Overall, CMR upwardly reclassified 28% of patients using the British Society of Echocardiography LVEF grading, 18.6% using the European Society of Cardiology heart failure classification, and 29.6% using specific reference ranges for each modality. In a multi-site "real-worldË® clinical setting, there was significant discrepancy between LVEFTTE and LVEFCMR measurement. Only 64.4% had their LVEF category confirmed by both imaging modalities. LVEFTTE was generally lower than LVEFCMR. LVEFCMR upwardly reclassified almost half of patients with severe LV dysfunction by LVEFTTE. Clinicians should consider the inter-modality variation before making therapeutic recommendations, particularly as clinical trial LVEF thresholds have historically been guided by echocardiography.