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BACKGROUND AND AIM: Epicardial adipose tissue (EAT) plays a role in coronary artery disease (CAD). EAT has regional distribution throughout the heart and each location may have a different genetic profile and function. Glucagon like peptide-1 receptor analogs (GLP-1RAs) reduce cardiovascular risk. However, the short-term effects of GLP-1RA on microRNA (miRNA) profile of each EAT location is unknown. Objective was to evaluate if EAT miRNAs were different between coronary (CORO-EAT), left atrial EAT (LA-EAT) and subcutaneous fat (SAT), and liraglutide can modulate EAT miRNAs expression. METHODS AND RESULTS: This was a 12-week randomized, double-blind, placebo-controlled study in 38 patients with type 2 diabetes (T2DM) and coronary artery disease (CAD) who were started on either liraglutide or placebo for a minimum of 4 up to 12 weeks prior to coronary artery by-pass grafting (CABG). Fat samples were collected during CABG. miR16, miR155 and miR181a were significantly higher in CORO-EAT and in LA-EAT than SAT (p < 0.01 and p < 0.05) in overall patients. miR16 and miR181-a were significantly higher in CORO-EAT than SAT (p < 0.01), and miR155 and miR181a were higher in LA-EAT than SAT (p < 0.05) in the liraglutide group. Liraglutide-treated patients had better intra-op glucose control than placebo (146 ± 21 vs 160 ± 21 mg/dl, p < 0.01). CONCLUSIONS: Our study shows that CORO- and LA-miRNAs profiles were significantly different than SAT miRNAs in overall patients and miRNAs were significantly higher in CORO-EAT and LA-EAT than SAT in the liraglutide group. Pre-op liraglutide was also associated with better intra operative glucose control than placebo independently of weight loss.
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Success rates for catheter ablation of atrial fibrillation (AF), particularly persistent AF, remain suboptimal. Pulmonary vein isolation has been the cornerstone for catheter ablation of AF for over a decade. While successful for most patients, pulmonary vein isolation alone is still insufficient for a substantial minority. Frustratingly, multiple clinical trials testing a diverse array of additional ablation approaches have led to mixed results, with no current strategy that improves AF outcomes beyond pulmonary vein isolation in all patients. Nevertheless, this large collection of data could be used to extract important insights regarding AF mechanisms and the diversity of the AF syndrome. Mechanistically, the general model for arrhythmogenesis prompts the need for tools to individually assess triggers, drivers, and substrates in individual patients. A key goal is to identify those who will not respond to pulmonary vein isolation, with novel approaches to phenotyping that may include mapping to identify alternative drivers or critical substrates. This, in turn, can allow for the implementation of phenotype-based, targeted approaches that may categorize patients into groups who would or would not be likely to respond to catheter ablation, pharmacological therapy, and risk factor modification programs. One major goal is to predict individuals in whom additional empirical ablation, while feasible, may be futile or lead to atrial scarring or proarrhythmia. This work attempts to integrate key lessons from successful and failed trials of catheter ablation, as well as models of AF, to suggest future paradigms for AF treatment.
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Fibrilación Atrial/cirugía , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/diagnóstico , Humanos , Ablación por Catéter/métodos , Ablación por Catéter/efectos adversos , Venas Pulmonares/cirugía , Venas Pulmonares/fisiopatología , Resultado del Tratamiento , Ensayos Clínicos como Asunto , Potenciales de Acción , Sistema de Conducción Cardíaco/fisiopatología , Sistema de Conducción Cardíaco/cirugía , Predicción , Frecuencia Cardíaca , Factores de RiesgoRESUMEN
The identification of the pulmonary veins as a trigger source for atrial fibrillation (AF) has established pulmonary vein isolation (PVI) as a key target for AF ablation. However, PVI alone does not prevent recurrent AF in many patients, and numerous additional ablation strategies have failed to improve on PVI outcomes. This therapeutic limitation may be due, in part, to a failure to identify and intervene specifically on the pro-fibrillatory substrate within the atria and pulmonary veins. In this review paper, we highlight several emerging approaches with clinical potential that target atrial cardiomyopathy-the underlying anatomic, electrical, and/or autonomic disease affecting the atrium-in various stages of practice and investigation. In particular, we consider the evolving roles of risk factor modification, targeting of epicardial adipose tissue, tissue fibrosis, oxidative stress, and the inflammasome, along with aggressive early anti-AF therapy in AF management. Attention to combatting substrate development promises to improve outcomes in AF.
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Fibrilación Atrial , Fibrilación Atrial/terapia , Fibrilación Atrial/fisiopatología , Humanos , Ablación por Catéter/métodos , Venas Pulmonares/cirugíaRESUMEN
BACKGROUND: Long-term anticoagulation (AC) therapy reduces the risk of stroke in patients with Atrial Fibrillation (AF). However, data on the impact of AC on in-hospital stroke outcomes is lacking. METHODS: The National Inpatient Sample was used to identify adult inpatients with AF and a primary diagnosis of ischemic stroke between 2016 and 2020. Data was stratified between AC users and nonusers. A multivariate regression model was used to describe the in-hospital outcomes, adjusting for significant comorbidities. RESULTS: A total of 655,540 hospitalizations with AF and a primary hospitalization diagnosis of ischemic stroke were included, of which 194,560 (29.7 %) were on long-term AC. Patients on AC tended to be younger (mean age, 77 vs. 78), had a higher average CHA2DS2VASc score (4.48 vs. 4.20), higher rates of hypertension (91 % vs. 88 %), hyperlipidemia (64 % vs. 59 %), and heart failure (34 % vs. 30 %) compared to patients not on long-term AC. Use of AC was associated with decreased in-hospital mortality (aOR [95 % CI]: 0.62 [0.60-0.63]), decreased stroke severity (mean NIHSS, 8 vs. 10), decreased use of tPA (aOR 0.42 [0.41-0.43]), mechanical thrombectomy (aOR 0.85 [0.83-0.87]), intracranial hemorrhage (aOR 0.69 [0.67-0.70]), gastrointestinal bleeding (aOR 0.74 [0.70-0.77]), and discharge to skilled nursing facilities (aOR 0.90 [0.89-0.91]), compared to patients not on AC (P<0.001 for all comparisons). CONCLUSION: Among patients with AF admitted for acute ischemic stroke, AC use prior to stroke was associated with decreased in-hospital mortality, decreased stroke severity, decreased discharge to SNF, and fewer stroke-related and bleeding complications.
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Anticoagulantes , Fibrilación Atrial , Bases de Datos Factuales , Mortalidad Hospitalaria , Accidente Cerebrovascular Isquémico , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/mortalidad , Fibrilación Atrial/complicaciones , Masculino , Femenino , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/diagnóstico , Anciano , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Factores de Riesgo , Resultado del Tratamiento , Anciano de 80 o más Años , Estados Unidos/epidemiología , Medición de Riesgo , Factores de Tiempo , Persona de Mediana Edad , Estudios Retrospectivos , Comorbilidad , Pacientes Internos , Esquema de MedicaciónRESUMEN
BACKGROUND: The goal was to determine the feasibility of mapping the injured-but-not-infarcted myocardium using 99mTc-duramycin in the postischemic heart, with spatial information for its characterization as a pathophysiologically intermediate tissue, which is neither normal nor infarcted. METHODS AND RESULTS: Coronary occlusion was conducted in Sprague Dawley rats with preconditioning and 30-minute ligation. In vivo single-photon emission computed tomography was acquired after 3 hours (n=6) using 99mTc-duramycin, a phosphatidylethanolamine-specific radiopharmaceutical. The 99mTc-duramycin+ areas were compared with infarct and area-at-risk (n=8). Cardiomyocytes and endothelial cells were isolated for gene expression profiling. Cardiac function was measured with echocardiography (n=6) at 4 weeks. In vivo imaging with 99mTc-duramycin identified the infarct (3.9±2.4% of the left ventricle and an extensive area 23.7±2.2% of the left ventricle) with diffuse signal outside the infarct, which is pathologically between normal and infarcted (apoptosis 1.8±1.6, 8.9±4.2, 13.6±3.8%; VCAM-1 [vascular cell adhesion molecule 1] 3.2±0.8, 9.8±4.1, 15.9±4.2/mm2; tyrosine hydroxylase 14.9±2.8, 8.6±4.4, 5.6±2.2/mm2), with heterogeneous changes including scattered micronecrosis, wavy myofibrils, hydropic change, and glycogen accumulation. The 99mTc-duramycin+ tissue is quantitatively smaller than the area-at-risk (26.7% versus 34.4% of the left ventricle, P=0.008). Compared with infarct, gene expression in the 99mTc-duramycin+-noninfarct tissue indicated a greater prosurvival ratio (BCL2/BAX [B-cell lymphoma 2/BCL2-associated X] 7.8 versus 5.7 [cardiomyocytes], 3.7 versus 3.2 [endothelial]), and an upregulation of ion channels in electrophysiology. There was decreased contractility at 4 weeks (regional fractional shortening -8.6%, P<0.05; circumferential strain -52.9%, P<0.05). CONCLUSIONS: The injured-but-not-infarcted tissue, being an intermediate zone between normal and infarct, is mapped in vivo using phosphatidylethanolamine-based imaging. The intermediate zone contributes significantly to cardiac dysfunction.
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Modelos Animales de Enfermedad , Infarto del Miocardio , Péptidos , Radiofármacos , Ratas Sprague-Dawley , Tomografía Computarizada de Emisión de Fotón Único , Animales , Infarto del Miocardio/patología , Infarto del Miocardio/metabolismo , Infarto del Miocardio/diagnóstico por imagen , Masculino , Miocardio/patología , Miocardio/metabolismo , Miocitos Cardíacos/patología , Miocitos Cardíacos/metabolismo , Bacteriocinas/metabolismo , Estudios de Factibilidad , Ratas , Perfilación de la Expresión Génica/métodos , Función Ventricular Izquierda , Células Endoteliales/metabolismo , Células Endoteliales/patología , Compuestos de OrganotecnecioRESUMEN
INTRODUCTION: Multiple analysis techniques evaluate electrograms during atrial fibrillation (AF), but none have been established to guide catheter ablation. This study compares electrogram properties recorded from multiple right (RA) and left atrial (LA) sites. METHODS: Multisite LA/RA mapping (281 ± 176/239 ± 166 sites/patient) was performed in 42 patients (30 males, age 63 ± 9 years) undergoing first (n = 32) or redo-AF ablation (n = 10). All electrogram recordings were visually reviewed and artifactual signals were excluded leaving a total of 21 846 for analysis. Electrogram characteristics evaluated were cycle length (CL), amplitude, Shannon's entropy (ShEn), fractionation interval, dominant frequency, organizational index, and cycle length of most recurrent morphology (CLR ) from morphology recurrence plot analysis. RESULTS: Electrogram characteristics were correlated to each other. All pairwise comparisons were significant (p < .001) except for dominant frequency and CLR (p = .59), and amplitude and dominant frequency (p = .38). Only ShEn and fractionation interval demonstrated a strong negative correlation (r = -.94). All other pairwise comparisons were poor to moderately correlated. The relationships are highly conserved among patients, in the RA versus LA, and in those undergoing initial versus redo ablations. Antiarrhythmic drug therapy did not have a significant effect on electrogram characteristics, except minimum ShEn. Electrogram characteristics associated with ablation outcome were shorter minimum CLR , lower minimum ShEn, and longer mimimum CL. There was minimal overlap between the top 10 sites identified by one electrogram characteristic and the top 10 sites identified by the other 10 characteristics. CONCLUSION: Multiple techniques can be employed for electrogram analysis in AF. In this analysis of eight different electrogram characteristics, seven were poorly to moderately correlated and do not identify similar locations. Only some characteristics were predictive of ablation outcome. Further studies to consider electrogram properties, perhaps in combination, for categorizing and/or mapping AF are warranted.
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Apéndice Atrial , Fibrilación Atrial , Ablación por Catéter , Masculino , Humanos , Persona de Mediana Edad , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Atrios Cardíacos , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodosRESUMEN
BACKGROUND: There are no standard mapping approaches for patients with persistent atrial fibrillation (PeAF), particularly after failed prior catheter ablation (CA). In this study, we assess the feasibility of using Electrogram Morphology Recurrence (EMR) to guide ablation. METHODS: Ten patients with recurrent PeAF after prior CA underwent detailed mapping of both atria during PeAF using the PentaRay (4 mm interelectrode spacing) and 3D mapping with CARTO. At each site, 15 s recordings were made. Custom software identified each electrogram and cross-correlation was used to identify the most recurrent electrogram morphology from which the % recurrence and cycle length of the most repeatable morphology (CLR) was calculated. Sites of shortest CLR and sites within 5 ms of shortest CLR with recurrence ≥ 80% were used to inform CA strategy. RESULTS: A mean of 342.9 ± 131.9 LA and 328.6 ± 91.5 RA sites were recorded per patient. Nine had PV reconnection. Shortest CLR sites guided ablation in 6/10 patients while 1 patient failed to fulfill shortest CLR criteria, and another 3 did not undergo CA guided by shortest CLR due to operator preference. On 12-month follow-up, all 4 patients without shortest CLR guided CA had recurrent PeAF. Of the 6 patients with shortest CLR guided CA, 5 patients did not have recurrent PeAF (p = 0.048), although 1 had paroxysmal AF and 2 had atypical atrial flutter. CONCLUSION: EMR is a feasible, novel technique to guide CA in patients with PeAF. Further evaluation is needed to provide an electrogram-based method for mapping guided targeted ablation of key areas.
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Humanos , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Resultado del Tratamiento , Recurrencia , Atrios Cardíacos/cirugía , Ablación por Catéter/métodos , Venas Pulmonares/cirugíaRESUMEN
BACKGROUND AND AIM: Visceral fat is an independent predictor of the cardiovascular risk in subjects with type 2 diabetes (T2DM), but it is rarely assessed during an outpatient visit. Epicardial fat (EAT), the visceral fat of the heart, plays a role in coronary artery disease (CAD). EAT thickness can be clinically assessed with standard ultrasound. In this study we sought to evaluate the association of ambulatory ultrasound measured EAT thickness with CAD in asymptomatic well controlled T2DM subjects on metformin monotherapy during outpatient visits. METHODS AND RESULTS: This was single center, pragmatic study in 142 T2DM patients. Each subject underwent baseline ultrasound EAT thickness measurement, anthropometric and biomarkers. The incidence of CAD was detected after 1 year. At baseline, HbA1c was 6.7 % and BMI 34.9 kg/m2, EAT thickness was 8.3 ± 2.3 in women and 9.4 ± 2.4 mm in men, higher than threshold values for high cardiovascular risk. In multivariate models, EAT was the only statistically significant correlate of CAD at 1-year f/u (p = 0.04). CONCLUSIONS: Point of care ultrasound measured EAT thickness is a good correlate of CAD in well controlled and asymptomatic T2DM subjects on metformin monotherapy. EAT thickness predicted CAD better than traditional risk factors, such as BMI, HbA1c, age, blood pressure or duration of diabetes.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 2 , Metformina , Masculino , Humanos , Femenino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Tejido Adiposo Epicárdico , Hemoglobina Glucada , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Metformina/uso terapéutico , Atención AmbulatoriaRESUMEN
Beta blockers are uniformly recommended for all patients after myocardial infarction (MI), including those with diabetes mellitus (DM). This study assesses the impact of ß-blocker type and dosing on survival in patients with DM after MI. A cohort of 6,682 patients in the Outcomes of Beta-blocker Therapy After Myocardial INfarction registry were discharged after MI. In this cohort, 2,137 patients had DM (32%). Beta-blocker dose was indexed to the target daily dose used in randomized clinical trials and reported as percentage. Dosage groups were: no ß blocker, >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of the target dose. The overall mean discharge ß-blocker dose in patients with DM was 42.7 ± 34.1% versus 35.9 ± 27.4% in patients without DM (p <0.0001). Patients with DM were prescribed carvedilol at a higher rate than those without DM (27.8% vs 19.6%). The 3-year mortality estimates were 24.4% and 12.8% for patients with DM versus without DM (p <0.0001), respectively, with an unadjusted hazard ratio = 1.820 (confidence interval 1.587 to 2.086, p <0.0001). Patients with DM in the >12.5% to 25% dose category had the highest survival rates, whereas patients in the >50% dose had the lowest survival rate among patients discharged on ß blockers (p <0.0001). In the multivariable analysis among patients with DM after MI, all ß-blocker dose categories demonstrated lower mortality than no therapy; however, only the >12.5% to 25% dose had a statistically significant hazard ratio 0.450 (95% confidence interval 0.224 to 0.907, p = 0.025). In patients with DM, there was no statistically significant difference in 3-year mortality among those treated with metoprolol versus carvedilol. In conclusion, our analysis in patients with DM after MI suggested a survival benefit from ß-blocker therapy, with no apparent advantage to high- versus low-dose ß-blocker therapy; although, physicians tended to prescribe higher doses in patients with DM. There was no survival benefit for carvedilol over metoprolol in patients with DM.
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Diabetes Mellitus , Infarto del Miocardio , Humanos , Carvedilol/uso terapéutico , Metoprolol/uso terapéutico , Infarto del Miocardio/complicaciones , Infarto del Miocardio/tratamiento farmacológico , Antagonistas Adrenérgicos beta , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Diabetes Mellitus/inducido químicamenteRESUMEN
Traditional anatomically guided ablation and attempts to perform electrogram-guided atrial fibrillation (AF) ablation (CFAE, DF, and FIRM) have not been shown to be sufficient treatment for persistent AF. Using biatrial high-density electrophysiologic mapping in a canine rapid atrial pacing model of AF, we systematically investigated the relationship of electrogram morphology recurrence (EMR) (Rec% and CLR) with established AF electrogram parameters and tissue characteristics. Rec% correlates with stability of rotational activity and with the spatial distribution of parasympathetic nerve fibers. These results have indicated that EMR may therefore be a viable therapeutic target in persistent AF.
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AIMS: Human epicardial adipose tissue (EAT) plays a crucial role in the development and progression of coronary artery disease, atrial fibrillation, and heart failure. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular, and immune cells. Epicardial adipose tissue is a white adipose tissue, albeit it also has brown fat-like or beige fat-like features. No muscle fascia divides EAT and myocardium; this allows a direct interaction and crosstalk between the epicardial fat and the myocardium. Thus, it might be a therapeutic target for pharmaceutical compounds acting on G-protein-coupled receptors, such as those for glucose-dependent insulinotropic polypeptide (GIP), glucagon (GCG), and glucagon-like peptide-1 (GLP-1), whose selective stimulation with innovative drugs has demonstrated beneficial cardiovascular effects. The precise mechanism of these novel drugs and their tissue and cellular target(s) need to be better understood. We evaluate whether human EAT expresses GIP, GCG, and GLP-1 receptors and whether their presence is related to EAT transcriptome. We also investigated protein expression and cell-type localization specifically for GIP receptor (GIPR) and glucagon receptor (GCGR). METHODS AND RESULTS: Epicardial adipose tissue samples were collected from 33 patients affected by cardiovascular diseases undergoing open heart surgery (90.9% males, age 67.2 ± 10.5 years mean ± SD). Microarray and immunohistochemistry analyses were performed. Microarray analysis showed that GIPR and GCGR messenger ribonucleic acids (mRNAs) are expressed in EAT, beyond confirming the previously found GLP-1 [3776 ± 1377 arbitrary unit (A.U.), 17.77 ± 14.91 A.U., and 3.41 ± 2.27 A.U., respectively]. The immunohistochemical analysis consistently indicates that GIPR and GCGR are expressed in EAT, mainly in macrophages, isolated, and in crown-like structures. In contrast, only some mature adipocytes of different sizes showed cytoplasmic immunostaining, similar to endothelial cells and pericytes in the capillaries and pre-capillary vascular structures. Notably, EAT GIPR is statistically associated with the low expression of genes involved in free fatty acid (FFA) oxidation and transport and those promoting FFA biosynthesis and adipogenesis (P < 0.01). Epicardial adipose tissue GCGR, in turn, is related to genes involved in FFA transport, mitochondrial fatty acid oxidation, and white-to-brown adipocyte differentiation, in addition to genes involved in the reduction of fatty acid biosynthesis and adipogenesis (P < 0.01). CONCLUSIONS: Having reported the expression of the GLP-1 receptor previously, here, we showed that GIPR and GCGR similarly present at mRNA and protein levels in human EAT, particularly in macrophages and partially adipocytes, suggesting these G-protein-coupled receptors as pharmacological targets on the ongoing innovative drugs, which seem cardiometabolically healthy well beyond their effects on glucose and body weight.
Human epicardial adipose tissue (EAT) is a unique and multifunctional fat compartment of the heart. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular, and immune cells. Epicardial adipose tissue is a white adipose tissue, albeit it also has brown fat-like or beige fat-like features. No muscle fascia divides EAT and myocardium; this allows a direct interaction and crosstalk between the epicardial fat and the myocardium. Due to its distinctive transcriptome and functional proximity to the heart, EAT can play a key role in the development and progression of coronary artery disease, atrial fibrillation, and heart failure. Clinically, EAT, given its rapid metabolism and simple measurability, can be considered a novel therapeutic target, owing to its responsiveness to drugs with pleiotropic and clear beneficial cardiovascular effects such as the glucagon-like peptide-1 receptor (GLP-1R) agonists.Human EAT is found to express the genes encoding the receptors of glucose-dependent insulinotropic polypeptide receptor (GIPR), glucagon receptor (GCGR), and GLP-1. The immunohistochemistry indicates that GIP and GCG receptor proteins are present in EAT samples. Epicardial adipose tissue GIPR is inversely associated with genes involved in free fatty acid (FFA) oxidation and transport and with genes promoting FFA biosynthesis and adipogenesis. Epicardial adipose tissue GCGR is correlated with genes promoting FFA transport and activation for mitochondrial beta-oxidation and white-to-brown adipocyte differentiation and with genes reducing FFA biosynthesis and adipogenesis.As the myocardium relies mostly on FFAs as fuel and is in direct contiguity with EAT, these findings may have a great importance for the modulation of the myocardial activity and performance. Given the emerging use and cardiovascular effects of GLP-1R agonists, dual GIPR/GLP-1R agonists, and GLP-1R/GIPR/GCGR triagonists, we believe that pharmacologically targeting and potentially modulating organ-specific fat depots through G-proteincoupled receptors may produce beneficial cardiovascular and metabolic effects.
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Receptor del Péptido 1 Similar al Glucagón , Glucagón , Masculino , Humanos , Persona de Mediana Edad , Anciano , Femenino , Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/genética , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Células Endoteliales/metabolismo , Tejido Adiposo/metabolismo , Polipéptido Inhibidor Gástrico/metabolismo , Polipéptido Inhibidor Gástrico/farmacología , Péptido 1 Similar al Glucagón , Receptores Acoplados a Proteínas G/genética , Glucosa , Ácidos GrasosRESUMEN
OBJECTIVE: Our purpose was to examine the association between beta-blocker dose and mortality following acute myocardial infarction. METHODS: This nationwide cohort study enrolled all patients admitted for first-time acute myocardial infarction in Denmark between July 1, 2004 and December 31, 2014, using the Danish National Patient Registry. Patients alive 15 days after admission were followed until death, emigration, or December 31, 2014. Patients were categorized according to daily beta-blocker consumption (0%, >0%-12.5%, >12.5%-25%, >25%-50%, >50%-100%, or >100% of the currently recommended target dose) based on prescriptions registered in the Danish National Database of Reimbursed Prescriptions. Doses were continuously updated during follow-up. Mortality rate ratios (MRRs) were computed and adjusted for confounders using Cox proportional hazard regression. RESULTS: Among 65,125 patients followed, any beta-blocker dose was associated with significant mortality reduction compared with no treatment (adjusted MRR ≤ 0.92 [95% confidence interval {CI}: 0.86-0.98]). The largest reduction was observed within the first year for beta-blocker doses >25%-50% (adjusted MRR = 0.55 [95% CI: 0.50-0.60]). After 1 year, doses >50%-100% were associated with the largest mortality reduction (adjusted MRR = 0.58 [95% CI: 0.50-0.67]), but it did not differ significantly from that associated with doses >25%-50% (adjusted MRR = 0.68 [95% CI: 0.61-0.77]). CONCLUSIONS: Any beta-blocker dose was associated with significant mortality reduction following acute myocardial infarction compared with no treatment. Doses >25%-50% of the currently recommended target dose were associated with maximal mortality reduction within the first year after acute myocardial infarction, suggesting that higher doses are unnecessary.
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Infarto del Miocardio , Humanos , Estudios de Seguimiento , Estudios de Cohortes , Antagonistas Adrenérgicos beta/uso terapéutico , Sistema de RegistrosRESUMEN
BACKGROUND: Electrogram (EGM) morphology recurrence (EMR) mapping of persistent atrial fibrillation (AF) quantifies consistency of activation and is expected to be high and rapid near AF drivers. OBJECTIVES: The purpose of this study was to compare EMR in left atria (LA) and right atria (RA) in patients undergoing first vs redo ablation for persistent AF. METHODS: Multisite LA/RA mapping (LA: 281 ± 176 sites/patient; RA: 239 ± 166 sites/patient) before persistent AF ablation was performed in 42 patients (30 males, age 63 ± 9 years) undergoing first (Group 1, n = 32) or redo ablation (Group 2, n = 10). After cross-correlation of each automatically detected EGM with every other EGM per recording, the most recurrent electrogram morphology was identified and its frequency (Rec%) and recurrence cycle length (CLR) were computed. RESULTS: In Groups 1 and 2, minimum CLR was 172.8 ± 26.0 milliseconds (LA: 178.2 ± 37.6 milliseconds, RA: 204.4 ± 34.0 milliseconds, P = 0.0005) and 186.5 ± 28.3 milliseconds (LA: 196.1 ± 38.1 milliseconds vs RA: 199.0 ± 30.2 milliseconds, P = 0.75), with Rec% 94.7% ± 10% and 93.8% ± 9.2%. Group 2 minimum CLR was not different from Group 1 (P = 0.20). Shortest CLR was in the LA in 84% of Group 1 and 50% of Group 2 patients (P = 0.04). Only 1 of 10 patients in Group 2 had the shortest CLR in the pulmonary veins (PVs) compared with 19 of 32 in Group 1 (P = 0.01). Most sites (77.6%) had Rec% <50%. CONCLUSIONS: EMR identified the shortest CLR sites in the PVs in 59% of patients undergoing initial persistent AF ablation, consistent with reported success rates of â¼50% for PV isolation. The majority of sites have low recurrence and may reflect bystander sites not critical for maintaining AF. EMR provides a robust new method for quantifying consistency and rapidity of activation direction at multiple atrial sites.
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Apéndice Atrial , Fibrilación Atrial , Ablación por Catéter , Masculino , Humanos , Persona de Mediana Edad , Anciano , Fibrilación Atrial/cirugía , Técnicas Electrofisiológicas Cardíacas/métodos , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/cirugía , Apéndice Atrial/cirugía , Ablación por Catéter/métodosRESUMEN
A 35-year-old woman with history of cardiovascular disease presented with shortness of breath, lightheadedness, fatigue, chest pain, and premature ventricular contractions 3 weeks after her second COVID-19 vaccine. Symptoms subsided following catheter ablation and ibuprofen except for chest pain and fatigue, which persisted following ablation and subsequent SARS-CoV-2 infection. The case suggests causal associations between COVID-19 vaccine/infection and recurrence of cardiovascular disease, including long-COVID-like symptoms. (Level of Difficulty: Advanced.).
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BACKGROUND: Predictors of in-hospital mortality after myocardial infarction (MI) have been reported dichotomously: survival vs death. Predictors of time from admission to death have not been reported. METHODS: A total of 7335 patients were enrolled in a prospective multicentre registry of acute MI. In-hospital mortality was classified by time from admission as acute (≤ 2 days), subacute (3 to 7 days), late (8 to 14 days), and very late (≥ 15 days) to identify factors associated with time to death in patients who died before discharge. Patient and MI characteristics, in-hospital interventions, and electrocardiographic findings were screened for differences in time to in-hospital death. RESULTS: In-hospital death affected 351 patients (4.8%). Mean age was 72.0 ± 12.4 years, and 40.5% were female patients. Median survival was 5 days (interquartile range: 2-12), and 41% of in-hospital deaths occurred after 1 week. Cardiac biomarkers and ejection fraction were not related to time to in-hospital death. Previous MI, systolic blood pressure, pharmacologic therapy, and interventional treatments were different among the 4 groups. The factors associated with late in-hospital death were coronary artery bypass graft surgery (CABG), new-onset atrial fibrillation or flutter, heart failure or pulmonary edema, bleeding, and lung disease. Acute and subacute in-hospital death was associated with ST-elevation MI, lower systolic blood pressure, and cardiac arrest on admission. CABG was performed in 12% of post-MI patients who died in hospital. CONCLUSIONS: Clinical risk factors for in-hospital mortality evolve over time immediately after acute MI. Understanding the time-dependent risk factors may allow for the development of new approaches to curtail the "later" in-hospital mortality.
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Infarto del Miocardio , Humanos , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Mortalidad Hospitalaria , Estudios Prospectivos , Puente de Arteria Coronaria/efectos adversos , Sistema de RegistrosRESUMEN
BACKGROUND: Following catheter ablation for atrial fibrillation (AF), there are dynamic changes in the atrial myocardium associated with damage to and necrosis of atrial tissue and other procedure related changes in rhythm and anticoagulation. Early time-dependent changes in biomarkers of necrosis, inflammation, and coagulation have been reported. This study examines mid-term (4-8 weeks post-ablation) changes in biomarkers and explores their ability to predict AF recurrence at one-year. METHODS: Twenty-seven patients (mean age 65.4 ± 9.7 years, 30% female) undergoing catheter ablation for AF had peripheral venous blood samples obtained at the time of ablation and 4-8 weeks later. All samples were processed to obtain plasma which was frozen for subsequent analysis. Coagulation studies were performed at the Northwestern Special Hemostasis Laboratory: VWF, ADAMTS13, PAI-1, D-dimer, and TAT complexes. A commercial lab analyzed samples for CRP, cystatin C, fibrinogen, galectin, IL-6, MMP-2, myoglobin, NT-proBNP, PAI-1, TIMP-1, TIMP-2, TPA, and VWF. RESULTS: Significant changes were noted with higher levels of ADAMTS13 (p < 0.0001), fibrinogen (p = 0.004), MMP-2 (p = 0.0002), TIMP-2 (p = 0.003), and TPA (p = 0.001) compared to lower levels of TAT (p < 0.0001) and NT-proBNP (p = 0.0001) at follow up post-ablation. One year after ablation, AF had recurred in 11/26 (42%) of patients. None of the biomarker changes predicted the 1-year outcome, and there was no significant association with the use of warfarin versus rivaroxaban. CONCLUSION: In patients undergoing catheter ablation for AF, there were significant changes in pre- vs post-ablation levels of multiple biomarkers. However, these changes were not associated with 1-year outcome of AF recurrence.
Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Fibrilación Atrial/cirugía , Metaloproteinasa 2 de la Matriz , Inhibidor Tisular de Metaloproteinasa-2 , Resultado del Tratamiento , Inhibidor 1 de Activador Plasminogénico , Factor de von Willebrand , Biomarcadores , Ablación por Catéter/métodos , RecurrenciaRESUMEN
Background The pathways of diastolic dysfunction and heart failure with preserved ejection fraction driven by lipotoxicity with metabolic syndrome are incompletely understood. Thus, there is an urgent need for animal models that accurately mimic the metabolic and cardiovascular phenotypes of this phenogroup for mechanistic studies. Methods and Results Hyperlipidemia was induced in WT-129 mice by 4 weeks of biweekly poloxamer-407 intraperitoneal injections with or without a single intravenous injection of adeno-associatedvirus 9-cardiac troponin T-low-density lipoprotein receptor (n=31), or single intravenous injection with adeno-associatedvirus 9-cardiac troponin T-low-density lipoprotein receptor alone (n=10). Treatment groups were compared with untreated or placebo controls (n=37). Echocardiography, blood pressure, whole-body plethysmography, ECG telemetry, activity wheel monitoring, and biochemical and histological changes were assessed at 4 to 8 weeks. At 4 weeks, double treatment conferred diastolic dysfunction, preserved ejection fraction, and increased left ventricular wall thickness. Blood pressure and whole-body plethysmography results were normal, but respiration decreased at 8 weeks (P<0.01). ECG and activity wheel monitoring, respectively, indicated heart block and decreased exercise activity (P<0.001). Double treatment promoted elevated myocardial lipids including total cholesterol, fibrosis, increased wet/dry lung (P<0.001) and heart weight/body weight (P<0.05). Xanthelasma, ascites, and cardiac ischemia were evident in double and single (p407) groups. Sudden death occurred between 6 and 12 weeks in double and single (p407) treatment groups. Conclusions We present a novel model of heart failure with preserved ejection fraction driven by dyslipidemia where mice acquire diastolic dysfunction, arrhythmia, cardiac hypertrophy, fibrosis, pulmonary congestion, exercise intolerance, and preserved ejection fraction in the absence of obesity, hypertension, kidney disease, or diabetes. The model can be applied to dissect pathways of metabolic syndrome that drive diastolic dysfunction in this lipotoxicity-mediated heart failure with preserved ejection fraction phenogroup mimic.