Contemporary outcomes of acute ischemic stroke in atrial fibrillation patients on anticoagulation.

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.

Targeting the Substrate for Atrial Fibrillation: JACC Review Topic of the Week.

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.

In Vivo Mapping of Myocardial Injury Outside the Infarct Zone: Tissue at an Intermediate Pathological State.

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.

Electrogram morphology recurrence guided catheter ablation for repeat ablation of persistent atrial fibrillation.

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.

Comparison of electrogram characteristics in persistent atrial fibrillation.

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.

Epicardial fat thickness in type 2 diabetes outpatient care.

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.

Impact of Diabetes Mellitus on Benefit of ß-Blocker Therapy After Myocardial Infarction.

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.

Regions of Highly Recurrent Electrogram Morphology With Low Cycle Length Reflect Substrate for Atrial Fibrillation.

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.

Long-Term Follow-Up After Acute Myocardial Infarction According to Beta-Blocker Dose.

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.

Human epicardial adipose tissue expresses glucose-dependent insulinotropic polypeptide, glucagon, and glucagon-like peptide-1 receptors as potential targets of pleiotropic therapies.

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.

Electrogram Morphology Recurrence for Mapping Persistent Atrial Fibrillation: Initial vs Redo Catheter Ablation.

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 ∼50% 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.

Determinants of Early and Late In-Hospital Mortality After Acute Myocardial Infarction: A Subanalysis of the OBTAIN Registry.

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.

Effects of catheter ablation of atrial fibrillation on the biomarker profile.

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.

Autoimmune Reaction Associated With Long COVID Syndrome and Cardiovascular Disease: A Genetic Case Report.

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.).

Mouse Model of Heart Failure With Preserved Ejection Fraction Driven by Hyperlipidemia and Enhanced Cardiac Low-Density Lipoprotein Receptor Expression.

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.

Sinus Tachycardia: a Multidisciplinary Expert Focused Review.

Sinus tachycardia (ST) is ubiquitous, but its presence outside of normal physiological triggers in otherwise healthy individuals remains a commonly encountered phenomenon in medical practice. In many cases, ST can be readily explained by a current medical condition that precipitates an increase in the sinus rate, but ST at rest without physiological triggers may also represent a spectrum of normal. In other cases, ST may not have an easily explainable cause but may represent serious underlying pathology and can be associated with intolerable symptoms. The classification of ST, consideration of possible etiologies, as well as the decisions of when and how to intervene can be difficult. ST can be classified as secondary to a specific, usually treatable, medical condition (eg, pulmonary embolism, anemia, infection, or hyperthyroidism) or be related to several incompletely defined conditions (eg, inappropriate ST, postural tachycardia syndrome, mast cell disorder, or post-COVID syndrome). While cardiologists and cardiac electrophysiologists often evaluate patients with symptoms associated with persistent or paroxysmal ST, an optimal approach remains uncertain. Due to the many possible conditions associated with ST, and an overlap in medical specialists who see these patients, the inclusion of experts in different fields is essential for a more comprehensive understanding. This article is unique in that it was composed by international experts in Neurology, Psychology, Autonomic Medicine, Allergy and Immunology, Exercise Physiology, Pulmonology and Critical Care Medicine, Endocrinology, Cardiology, and Cardiac Electrophysiology in the hope that it will facilitate a more complete understanding and thereby result in the better care of patients with ST.

Long-term cardiac surveillance and outcomes of COVID-19 patients.

Acute cardiac manifestions of COVID-19 have been well described, while chronic cardiac sequelae remain less clear. Various studies have shown conflicting data on the prevalence of new or worsening cardiovascular disease, myocarditis or cardiac dysrhythmias among patients recovered from COVID-19. Data are emerging that show that patients recovering from COVID-19 have an increased incidence of myocarditis and arrhythmias after recovery from COVID-19 compared with the control groups without COVID-19. The incidence of myocarditis after COVID-19 infection is low but is still significantly greater than the incidence of myocarditis from a COVID-19 vaccine. There have been several studies of athletes who underwent a variety of screening protocols prior to being cleared to return to exercise and competition. The data show possible, probable or definite myocarditis or cardiac injury among 0.4-3.0% of the athletes studied. Recent consensus statements suggest that athletes with full recovery and absence of cardiopulmonary symptoms may return to exercise and competition without cardiovascular testing. In conclusion, patients with COVID-19 may be expected to have an increased risk of cardiovascular disease, myocarditis or arrhythmias during the convalescent phase. Fortunately, the majority of patients, including athletes may return to their normal activity after recovery from COVID 19, in the absence of persisting cardiovascular symptoms.